View source for Hypothalamus

{{Short description|Area of the brain below the thalamus}}
{{Distinguish|Subthalamus|Hypophthalmus}}
{{Use dmy dates|date=August 2022}}
{{cs1 config |name-list-style=vanc|display-authors=6}}
{{Infobox Brain
| Name       = Hypothalamus
| Latin      = hypothalamus
| Image      = Hypothalamus.jpg
| Caption    = Location of the human hypothalamus
| Image2     = Hypothalamus Pituitary Complex hariadhi.svg
| Caption2   = Location of the hypothalamus (''cyan'') in relation to the pituitary and to the rest of the brain
| IsPartOf   = [[Brain]]
| Components =
| Artery     =
| Vein       =
}}
The '''hypothalamus''' ({{plural form}}: '''hypothalami'''; {{etymology|grc|''{{wikt-lang|grc|ὑπό}}'' ({{grc-transl|ὑπό}})|under||''{{wikt-lang|grc|θάλαμος}}'' ({{grc-transl|θάλαμος}})|chamber}}) is a small part of the [[vertebrate]] [[brain]] that contains a number of [[nucleus (neuroanatomy)|nuclei]] with a variety of functions. One of the most important functions is to link the [[nervous system]] to the [[endocrine system]] via the [[pituitary gland]]. The hypothalamus is located below the [[thalamus]] and is part of the [[limbic system]].<ref>{{Cite web|url= http://webspace.ship.edu/cgboer/limbicsystem.html|title= The Emotional Nervous System| vauthors = Boeree CG |website= General Psychology|access-date= 2016-04-18}}</ref> It forms the [[Basal (anatomy)|basal]] part of the [[diencephalon]]. All vertebrate brains contain a hypothalamus.<ref>{{cite journal | vauthors = Lemaire LA, Cao C, Yoon PH, Long J, Levine M | title = The hypothalamus predates the origin of vertebrates | journal = Science Advances | volume = 7 | issue = 18 | article-number = eabf7452 | date = April 2021 | pmid = 33910896 | pmc = 8081355 | doi = 10.1126/sciadv.abf7452 | bibcode = 2021SciA....7.7452L }}</ref> In humans, it is about the size of an [[Almond#Nut|almond]].<ref>{{cite journal | vauthors = Ishii M, Iadecola C | title = Metabolic and Non-Cognitive Manifestations of Alzheimer's Disease: The Hypothalamus as Both Culprit and Target of Pathology | journal = Cell Metabolism | volume = 22 | issue = 5 | pages = 761–776 | date = November 2015 | pmid = 26365177 | pmc = 4654127 | doi = 10.1016/j.cmet.2015.08.016 }}</ref>

The hypothalamus has the function of regulating certain [[metabolic]] [[biological process|processes]] and other activities of the [[autonomic nervous system]]. It [[biosynthesis|synthesizes]] and secretes certain [[neurohormone]]s, called [[releasing hormone]]s or hypothalamic hormones, and these in turn stimulate or inhibit the secretion of [[hormones]] from the pituitary gland. The hypothalamus controls [[thermoregulation|body temperature]], [[hunger (physiology)|hunger]], important aspects of parenting and [[maternal bond|maternal attachment behaviours]], [[thirst]],<ref>{{cite web|url= https://www.cancer.gov/publications/dictionaries/cancer-terms|title= NCI Dictionary of Cancer Terms|website= National Cancer Institute}}</ref> [[fatigue]], [[sleep]], [[circadian rhythm]]s, and is important in certain social behaviors, such as sexual and aggressive behaviors.<ref>{{cite journal | vauthors = Saper CB, Scammell TE, Lu J | title = Hypothalamic regulation of sleep and circadian rhythms | journal = Nature | volume = 437 | issue = 7063 | pages = 1257–1263 | date = October 2005 | pmid = 16251950 | doi = 10.1038/nature04284 | s2cid = 1793658 | bibcode = 2005Natur.437.1257S }}
</ref><ref name="motta2009"/>

==Structure==
The hypothalamus is divided into four regions (preoptic, supraoptic, tuberal, mammillary) in a parasagittal plane, indicating location anterior-posterior; and three zones (periventricular, intermediate, lateral) in the coronal plane, indicating location medial-lateral.<ref>{{Cite book | vauthors = Singh V |title=Textbook of Clinical Neuroanatomy |publisher=Elsevier Health Sciences |year=2014 |isbn=978-81-312-2981-1 |edition=2nd |page=134|url=https://books.google.com/books?id=LdCGBAAAQBAJ&dq=hypothalamus+regions++supraoptic%2C+tuberal%2C+mammillary&pg=PA134}}</ref> Hypothalamic nuclei are located within these specific regions and zones.<ref name="Singh2011">{{cite book|author=Inderbir Singh|title=Textbook of Anatomy: Volume 3: Head and Neck, Central Nervous System|url=https://books.google.com/books?id=8NJYL4ixFZQC&pg=PA1101|date=September 2011|publisher=JP Medical Ltd|isbn=978-93-5025-383-0|pages=1101–}}</ref> It is found in all vertebrate nervous systems. In mammals, [[magnocellular neurosecretory cell]]s in the [[paraventricular nucleus]] and the [[supraoptic nucleus]] of the hypothalamus produce [[neurohypophysial hormone]]s, [[oxytocin]] and [[vasopressin]].<ref name="Sukhov 1993">{{cite journal | vauthors = Sukhov RR, Walker LC, Rance NE, Price DL, Young WS | title = Vasopressin and oxytocin gene expression in the human hypothalamus | journal = The Journal of Comparative Neurology | volume = 337 | issue = 2 | pages = 295–306 | date = November 1993 | pmid = 8277003 | pmc = 9883978 | doi = 10.1002/cne.903370210 }}</ref> These hormones are released into the blood in the [[posterior pituitary]].<ref name=williams>{{cite book| vauthors = Melmed S, Polonsky KS, Larsen PR, Kronenberg HM |title=Williams Textbook of Endocrinology|date=2011|url=https://www.elsevier.com/books/williams-textbook-of-endocrinology/melmed/978-1-4377-0324-5|publisher=Saunders|page=107|isbn=978-1-4377-0324-5|edition=12th}}</ref> Much smaller [[parvocellular neurosecretory cell]]s, neurons of the paraventricular nucleus, release [[corticotropin-releasing hormone]] and other hormones into the [[hypophyseal portal system]], where these hormones diffuse to the [[anterior pituitary]].{{citation needed|date=September 2023}}

===Nuclei===
The hypothalamic nuclei include the following:<ref>{{cite web| website= psycheducation.org| url= http://www.psycheducation.org/emotion/pics/big%20hypothalamus.htm| title= Enlarged view of the hypothalamus |archive-url= https://web.archive.org/web/20051215094638/http://psycheducation.org/emotion/pics/big%20hypothalamus.htm |archive-date=15 December 2005| publisher= Jim Phelps |access-date= 2020-02-07}}</ref><ref>{{cite web| url= http://www.utdallas.edu/~tres/integ/hom3/display13_04.html |title= Emotion and the limbic system | website= utdallas.edu | publisher= Lucien T. "Tres" Thompson, [[The University of Texas at Dallas]] | access-date= 2020-02-07}}</ref>

{| class="wikitable"
|+ List of nuclei, their functions, and the neurotransmitters, neuropeptides, or hormones that they utilize
<!--This table needs to be restructured so as to separate the functions of a nucleus from the neurochemicals and hormones that mediate them; the compounds released by a particular nucleus should probably go into another column and it should be made clear whether a compound is released onto another neuron (i.e., a neuropeptide/neurotransmitter) or into the blood stream (i.e., a hormone)-->
|-
|'''Region'''
|'''Area'''
|'''Nucleus'''
|'''Function'''<ref>{{cite book| title= Guyton and Hall Textbook of Medical Physiology| vauthors = Hall JE, Guyton AC | isbn= 978-1-4160-4574-8| year= 2011| publisher= Saunders/Elsevier | edition= 12th}}</ref>
|-
|rowspan=8|Anterior (supraoptic)
| rowspan="2" | Preoptic<!--Per neurolex--> || [[Preoptic area|Preoptic nucleus]] ||
* [[Thermoregulation]]
|-
|[[Ventrolateral preoptic nucleus]]
|[[Sleep]]
|-
|rowspan=5|Medial
| [[Medial preoptic nucleus]] ||
* Regulates the release of gonadotropic hormones from the adenohypophysis
* Contains the [[sexually dimorphic nucleus]], which releases GnRH, differential development between sexes is based upon in utero testosterone levels
* Thermoregulation<ref>{{cite journal | vauthors = Yoshida K, Li X, Cano G, Lazarus M, Saper CB | title = Parallel preoptic pathways for thermoregulation | journal = The Journal of Neuroscience | volume = 29 | issue = 38 | pages = 11954–64 | date = September 2009 | pmid = 19776281 | pmc = 2782675 | doi = 10.1523/JNEUROSCI.2643-09.2009 }}</ref>
|-
| [[Supraoptic nucleus]] ||
* [[Vasopressin]] release
* [[Oxytocin]] release

|-
| [[Paraventricular nucleus]] ||
* [[thyrotropin-releasing hormone]] release
* [[corticotropin-releasing hormone]] release
* [[oxytocin]] release
* [[vasopressin]] release
* [[somatostatin]] round
* [[arousal]] (wakefulness and attention)<ref>{{cite journal | vauthors = Chen CR, Zhong YH, Jiang S, Xu W, Xiao L, Wang Z, Qu WM, Huang ZL | title = Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice | journal = eLife | volume = 10 | article-number = e69909 | date = November 2021 | pmid = 34787078 | pmc = 8631797 | doi = 10.7554/eLife.69909 | doi-access = free | veditors  = Elmquist JK, Wong ML, Lazarus M }}</ref><ref>{{cite journal | vauthors = Wang Z, Zhong YH, Jiang S, Qu WM, Huang ZL, Chen CR | title = Case Report: Dysfunction of the Paraventricular Hypothalamic Nucleus Area Induces Hypersomnia in Patients | language = English | journal = Frontiers in Neuroscience | volume = 16 | article-number = 830474 | date = 2022-03-14 | pmid = 35360167 | doi = 10.3389/fnins.2022.830474 | doi-access = free | pmc = 8964012 }}</ref>
* [[appetite]]

|-
| [[Anterior hypothalamic nucleus]] ||
* [[thermoregulation]]
* [[Thermoregulation|panting]]
* [[sweating]]
* [[thyrotropin]] inhibition
|-
| [[Suprachiasmatic nucleus]] ||
* [[Circadian rhythms]]
|-
|Lateral
| [[Lateral hypothalamic nucleus|Lateral nucleus]]|| See {{Section link|Lateral hypothalamus|Function}}&nbsp;– primary source of [[orexin]] neurons that project throughout the brain and spinal cord
|-
|rowspan=5|Middle (tuberal)
|rowspan=3|Medial
| [[Dorsomedial hypothalamic nucleus]] ||
* [[blood pressure]]
* [[heart rate]]
* [[gastrointestinal tract|GI]] stimulation
|-
| [[Ventromedial nucleus]] ||
* [[satiety]]
* [[neuroendocrine]] control
|-
| [[Arcuate nucleus]] ||
* [[Growth hormone-releasing hormone]] (GHRH)
* [[feeding]]
* [[Dopamine]]-mediated [[prolactin]] inhibition
|-
|rowspan=2| Lateral || [[Lateral hypothalamic nucleus|Lateral nucleus]] || See {{Section link|Lateral hypothalamus|Function}}&nbsp;– primary source of [[orexin]] neurons that project throughout the brain and spinal cord
|-
| [[Lateral tuberal nuclei]] ||
|-
|rowspan=4|Posterior (mammillary)
|rowspan=2|Medial
|Mammillary nuclei (part of [[mammillary body|mammillary bodies]]) ||
* [[memory]]
|-
| [[Posterior nucleus (hypothalamus)|Posterior nucleus]] ||
* Increase [[blood pressure]]
* [[pupil]]lary dilation
* [[shivering]]
* [[vasopressin]] release
|-
| rowspan=2 | Lateral
| [[Lateral hypothalamic nucleus|Lateral nucleus]] || See {{Section link|Lateral hypothalamus|Function}}&nbsp;– primary source of [[orexin]] neurons that project throughout the brain and spinal cord
|-
| [[Tuberomammillary nucleus]]<ref name="Histamine pathways">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors= Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher= McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | pages = 175–176 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote = Within the brain, histamine is synthesized exclusively by neurons with their cell bodies in the tuberomammillary nucleus (TMN) that lies within the posterior hypothalamus. There are approximately 64000 histaminergic neurons per side in humans. These cells project throughout the brain and spinal cord. Areas that receive especially dense projections include the cerebral cortex, hippocampus, neostriatum, nucleus accumbens, amygdala, and hypothalamus. &nbsp;... While the best characterized function of the histamine system in the brain is regulation of sleep and arousal, histamine is also involved in learning and memory&nbsp;... It also appears that histamine is involved in the regulation of feeding and energy balance.}}</ref> <!--Per neurolex and ref for this entry-->||
* [[arousal]] (wakefulness and attention)
* feeding and [[energy balance (biology)|energy balance]]
* learning
* memory
* [[sleep]]
|}

<gallery>
File:HIGHPVN.jpg|Cross-section of the monkey hypothalamus displays two of the major hypothalamic nuclei on either side of the fluid-filled third ventricle.
File:HypothalamicNuclei.PNG|Hypothalamic nuclei <!--Symbols: AC: anterior commissure PO: preoptic nucleus SC: suprachiasmatic nucleus OC: optic chiasma TC: tuber cinereum AP: anterior pituitary IN: infundibulum PP: posterior pituitary ME: median eminence AH: anterior hypothalamic nucleus SO: supraoptic nucleus TH: thalamus PV: paraventricular nucleus (not to be confused with periventricular nucleus, which is not shown) DM: dorsomedial nucleus VM: ventromedial nucleus AR: arcuate nucleus (associated with periventricular nucleus, which is not shown) LT: lateral nucleus PN: posterior nucleus MB: mamillary body-->
File:3D-Hypothalamus.JPG|Hypothalamic nuclei on one side of the hypothalamus, shown in a 3-D computer reconstruction<ref>Brain Research Bulletin 35:323–327, 1994</ref>
</gallery>

===Connections===
{{Further|Lateral hypothalamus#Orexinergic projection system|Tuberomammillary nucleus#Histaminergic outputs}}
The hypothalamus is highly interconnected with other parts of the [[central nervous system]], in particular the brainstem and its [[reticular formation]]. As part of the [[limbic system]], it has connections to other limbic structures including the [[amygdala]] and [[septum]], and is also connected with areas of the [[autonomous nervous system]]. {{citation needed|date=March 2025}}

The hypothalamus receives many inputs from the [[brainstem]], the most notable from the [[nucleus of the solitary tract]], the [[locus coeruleus]], and the [[ventrolateral medulla]]. {{citation needed|date=March 2025}}

'''Most''' nerve fibres within the hypothalamus run in two ways (bidirectional).
* Projections to areas [[Anatomical terms of location|caudal]] to the hypothalamus go through the [[medial forebrain bundle]], the [[mammillotegmental fasciculus|mammillotegmental tract]] and the [[dorsal longitudinal fasciculus]].
* Projections to areas rostral to the hypothalamus are carried by the [[mammillothalamic tract]], the [[Fornix of brain|fornix]] and [[terminal stria]].
* Projections to areas of the [[sympathetic nervous system|sympathetic motor system]] ([[lateral horn of spinal cord|lateral horn]] spinal segments T1–L2/L3) are carried by the [[hypothalamospinal tract]] and they activate the sympathetic motor pathway.

===Sexual dimorphism===
Several hypothalamic nuclei are [[sexually dimorphic]]; i.e., there are clear differences in both structure and function between males and females.<ref name="ReferenceA">{{cite journal | vauthors = Hofman MA, Swaab DF | title = The sexually dimorphic nucleus of the preoptic area in the human brain: a comparative morphometric study | journal = Journal of Anatomy | volume = 164 | pages = 55–72 | date = June 1989 | pmid = 2606795 | pmc = 1256598 }}</ref> Some differences are apparent even in gross neuroanatomy: most notable is the [[sexually dimorphic nucleus]] within the [[preoptic area]],<ref name="ReferenceA"/> in which the differences are subtle changes in the connectivity and chemical sensitivity of particular sets of neurons. The importance of these changes can be recognized by functional differences between males and females. For instance, males of most species prefer the odor and appearance of females over males, which is instrumental in stimulating male sexual behavior. If the sexually dimorphic nucleus is lesioned, this preference for females by males diminishes. Also, the pattern of secretion of [[growth hormone]] is sexually dimorphic;<ref>{{cite journal | vauthors = Quinnies KM, Bonthuis PJ, Harris EP, Shetty SR, Rissman EF | title = Neural growth hormone: Regional regulation by estradiol and / or sex chromosome complement in male and female mice | journal = Biology of Sex Differences | volume = 6 | article-number = 8 | year = 2015 | pmid = 25987976 | pmc = 4434521 | doi = 10.1186/s13293-015-0026-x | doi-access = free }}</ref> this is why in many species, adult males are visibly distinct sizes from females.

====Responsiveness to ovarian steroids====
Dimorphism is also found in physiological and behavioral responses to [[ovarian steroids]] in adults, where males and females respond to these hormones differently. For example, [[estrogen receptor]] sensitivity for different sets of neurons is dimorphic already early on in development.<ref name=":0">{{Cite journal |last1=van Veen |first1=J. Edward |last2=Kammel |first2=Laura G. |last3=Bunda |first3=Patricia C. |last4=Shum |first4=Michael |last5=Reid |first5=Michelle S. |last6=Massa |first6=Megan G. |last7=Arneson |first7=Douglas V. |last8=Park |first8=Jae W. |last9=Zhang |first9=Zhi |last10=Joseph |first10=Alexia M. |last11=Hrncir |first11=Haley |last12=Liesa |first12=Marc |last13=Arnold |first13=Arthur P. |last14=Yang |first14=Xia |last15=Correa |first15=Stephanie M. |date=2020-04-13 |title=Hypothalamic oestrogen receptor alpha establishes a sexually dimorphic regulatory node of energy expenditure |journal=Nature Metabolism |language=en |volume=2 |issue=4 |pages=351–363 |doi=10.1038/s42255-020-0189-6 |pmid=32377634 |pmc=7202561 |issn=2522-5812}}</ref> Hypothalamic dimorphism underlies some known behavioral differences in mice,<ref>{{Cite journal |last1=Spiteri |first1=Thierry |last2=Musatov |first2=Sergei |last3=Ogawa |first3=Sonoko |last4=Ribeiro |first4=Ana |last5=Pfaff |first5=Donald W. |last6=Agmo |first6=Anders |date=2010 |title=Estrogen-induced sexual incentive motivation, proceptivity and receptivity depend on a functional estrogen receptor alpha in the ventromedial nucleus of the hypothalamus but not in the amygdala |journal=Neuroendocrinology |volume=91 |issue=2 |pages=142–154 |doi=10.1159/000255766 |issn=1423-0194 |pmc=2918652 |pmid=19887773}}</ref> and has known physiological effects in humans, e.g. affecting thermoregulation<ref name=":0" /> and metabolism.<ref>{{Cite journal |last1=McArthur |first1=Simon |last2=McHale |first2=Emily |last3=Gillies |first3=Glenda E. |date=July 2007 |title=The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex- region- and time-specific manner |journal=Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology |volume=32 |issue=7 |pages=1462–1476 |doi=10.1038/sj.npp.1301277 |issn=0893-133X |pmid=17164817}}</ref> Although human hypothalami exhibit various sex differences,<ref>{{Cite journal |last1=Cosgrove |first1=Kelly P. |last2=Mazure |first2=Carolyn M. |last3=Staley |first3=Julie K. |date=2007-10-15 |title=Evolving knowledge of sex differences in brain structure, function, and chemistry |journal=Biological Psychiatry |volume=62 |issue=8 |pages=847–855 |doi=10.1016/j.biopsych.2007.03.001 |issn=0006-3223 |pmc=2711771 |pmid=17544382}}</ref> it is not certain which behaviors are caused, predisposed, and not caused by these.<ref name=":1">{{Cite journal |last=McCarthy |first=Margaret M. |date=2009-09-29 |title=Estradiol and the developing brain |journal=Physiological Reviews |volume=88 |issue=1 |pages=91–124 |doi=10.1152/physrev.00010.2007 |issn=0031-9333 |pmc=2754262 |pmid=18195084}}</ref><ref>{{Cite journal |last1=Gillies |first1=Glenda E. |last2=McArthur |first2=Simon |date=June 2010 |title=Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines |journal=Pharmacological Reviews |volume=62 |issue=2 |pages=155–198 |doi=10.1124/pr.109.002071 |issn=1521-0081 |pmc=2879914 |pmid=20392807}}</ref> In addition to [[confounding]] environmental factors,<ref>{{Cite journal |last1=Shepard |first1=Kathryn N. |last2=Michopoulos |first2=Vasiliki |last3=Toufexis |first3=Donna J. |last4=Wilson |first4=Mark E. |date=2009-05-25 |title=Genetic, epigenetic and environmental impact on sex differences in social behavior |journal=Physiology & Behavior |volume=97 |issue=2 |pages=157–170 |doi=10.1016/j.physbeh.2009.02.016 |issn=1873-507X |pmc=2670935 |pmid=19250945}}</ref> the hypothalamus also contributes to dimorphic human behaviors where the hypothalamus does not itself cause dimorphism, but rather exhibits conditional, dimorphic responses as part of greater [[Signal transduction|pathways]], such as the [[Hypothalamic–pituitary–adrenal axis|HPG-axis]]<ref>{{Cite journal |last1=Wibral |first1=Matthias |last2=Dohmen |first2=Thomas |last3=Klingmüller |first3=Dietrich |last4=Weber |first4=Bernd |last5=Falk |first5=Armin |date=2012-10-10 |editor-last=Krueger |editor-first=Frank |title=Testosterone Administration Reduces Lying in Men |journal=PLOS ONE |language=en |volume=7 |issue=10 |article-number=e46774 |doi=10.1371/journal.pone.0046774 |doi-access=free |issn=1932-6203 |pmc=3468628 |pmid=23071635 |bibcode=2012PLoSO...746774W }}</ref><ref name="Note01" group="Note" /> or the [[Hypothalamic–pituitary–adrenal axis|HPA-axis]].<ref>{{Cite journal |last1=Heck |first1=Ashley L. |last2=Handa |first2=Robert J. |date=2018-08-01 |title=Sex differences in the hypothalamic–pituitary–adrenal axis' response to stress: an important role for gonadal hormones |url=https://www.nature.com/articles/s41386-018-0167-9 |journal=Neuropsychopharmacology |language=en |volume=44 |issue=1 |pages=45–58 |doi=10.1038/s41386-018-0167-9 |pmid=30111811 |issn=1740-634X}}</ref><ref>{{Cite journal |last1=Sofer |first1=Yael |last2=Osher |first2=Esther |last3=Abu Ahmad |first3=Wiessam |last4=Yacobi Bach |first4=Michal |last5=Even Zohar |first5=Naomi |last6=Zaid |first6=Dana |last7=Golani |first7=Nehama |last8=Moshe |first8=Yaffa |last9=Tordjman |first9=Karen |last10=Stern |first10=Naftali |last11=Greenman |first11=Yona |date=2024 |title=Gender-affirming hormone therapy effect on cortisol levels in trans males and trans females |url=https://onlinelibrary.wiley.com/doi/abs/10.1111/cen.14985 |journal=Clinical Endocrinology |language=en |volume=100 |issue=2 |pages=164–169 |doi=10.1111/cen.14985 |pmid=37933843 |issn=1365-2265|url-access=subscription }}</ref><ref name="Note02" group="Note" />

[[Estrogen]] and [[progesterone]] can influence gene expression in particular neurons or induce changes in [[cell membrane]] potential and [[kinase]] activation, leading to diverse non-genomic cellular functions. Estrogen and [[progesterone]] bind to their cognate [[nuclear hormone receptor]]s, which translocate to the cell nucleus and interact with regions of DNA known as [[hormone response element]]s (HREs) or get tethered to another [[transcription factor]]'s binding site. Estrogen receptor (ER) has been shown to transactivate other transcription factors in this manner, despite the absence of an [[estrogen response element]] (ERE) in the proximal promoter region of the gene. In general, ERs and [[progesterone receptor]]s (PRs) are gene activators, with increased mRNA and subsequent protein synthesis following hormone exposure.{{citation needed|date=February 2013}}

Male and female brains differ in the distribution of estrogen receptors; this is [[Inductive reasoning|widely assumed]]<ref>{{Cite journal |last1=McCarthy |first1=Margaret M. |last2=Konkle |first2=Anne T. M. |date=2005-09-01 |title=When is a sex difference not a sex difference? |url=https://www.sciencedirect.com/science/article/pii/S0091302205000282 |journal=Frontiers in Neuroendocrinology |volume=26 |issue=2 |pages=85–102 |doi=10.1016/j.yfrne.2005.06.001 |issn=0091-3022|url-access=subscription }}</ref> to be caused by neonatal [[estradiol]] exposure, with some mechanisms being proven,<ref>{{Cite journal |last1=Todd |first1=Brigitte J. |last2=Schwarz |first2=Jaclyn M. |last3=McCarthy |first3=Margaret M. |date=December 2005 |title=Prostaglandin-E2: a point of divergence in estradiol-mediated sexual differentiation |journal=Hormones and Behavior |volume=48 |issue=5 |pages=512–521 |doi=10.1016/j.yhbeh.2005.07.011 |issn=0018-506X |pmid=16126205}}</ref> however the complete underlying mechanism remains uncertain.<ref name=":1" /> Estrogen and progesterone receptors show differential expression where they are found in neurons of the anterior and mediobasal hypothalamus, notably:
* the [[preoptic area]], where [[LHRH]] neurons are located, regulating dopamine responses and maternal behavior;<ref>{{cite journal | vauthors = Castañeyra-Ruiz L, González-Marrero I, Castañeyra-Ruiz A, González-Toledo JM, Castañeyra-Ruiz M, de Paz-Carmona H, Castañeyra-Perdomo A, Carmona-Calero EM | title = Luteinizing hormone-releasing hormone distribution in the anterior hypothalamus of the female rats | journal = ISRN Anatomy | volume = 2013 | pages = 1–6 | year = 2013 | pmid = 25938107 | pmc = 4392965 | doi = 10.5402/2013/870721 | doi-access = free }}</ref>
* the [[periventricular nucleus]], where [[somatostatin]] neurons are located, regulating stress levels;<ref>{{cite journal | vauthors = Isgor C, Cecchi M, Kabbaj M, Akil H, Watson SJ | title = Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates the neuroendocrine response to stress and is regulated by corticosterone |journal=Neuroscience|volume=121|issue=4|pages= 837–45 | year = 2003|pmid=14580933|doi=10.1016/S0306-4522(03)00561-X | s2cid = 31026141 }}</ref>
* the [[ventromedial hypothalamus]], which regulates hunger and sexual arousal.

===Development===
[[File:Gray654.png|thumbnail|Median sagittal section of brain of human embryo of three months]]
In neonatal life, gonadal steroids are thought to influence the development of the hypothalamus. For instance, they correlate with the ability of females to exhibit a normal reproductive cycle, and of males and females to display appropriate reproductive behaviors in adult life:
* If a female rat is given testosterone in the first few days of postnatal life, during the "critical period" of sex-steroid influence in rats, the hypothalamus is irreversibly defeminized and masculinized; the adult rat will be incapable of generating an [[LH surge]] in response to estrogen as is characteristic of females, but will be capable of exhibiting male sexual behaviors e.g. mounting a sexually receptive female.<ref name="jneuro">{{cite journal|vauthors= McCarthy MM, Arnold AP, Ball GF, Blaustein JD, De Vries GJ|title=Sex differences in the brain: the not so inconvenient truth|journal=The Journal of Neuroscience |volume=32|issue=7|pages=2241–7|date = February 2012|pmid =22396398|pmc=3295598|doi=10.1523/JNEUROSCI.5372-11.2012 }}</ref>
* By contrast, a male rat castrated just after birth will be feminized, and the adult will show typical female "receptive" sexual behavior in response to estrogen, that is, [[lordosis behavior]].<ref name=jneuro/>
* Masculinization and feminization can be distinguished from their complimentary de-feminization and de-masculinization, as neonatal treatment with [[Cyclooxygenase-2 inhibitor|COX2 inhibitors]] or [[Prostaglandin E2|PgE2]] makes it possible to create rats which exhibit neither sexual behaviour, or both, respectively.<ref name=":1" /> Some effects of combined masculinization and feminization on hypothalamic physiology are known,<ref name=":1" /><ref>{{Cite journal |last1=Speert |first1=Debra B. |last2=Konkle |first2=Anne T. M. |last3=Zup |first3=Susan L. |last4=Schwarz |first4=Jaclyn M. |last5=Shiroor |first5=Chaitanya |last6=Taylor |first6=Michael E. |last7=McCarthy |first7=Margaret M. |date=July 2007 |title=Focal adhesion kinase and paxillin: novel regulators of brain sexual differentiation? |journal=Endocrinology |volume=148 |issue=7 |pages=3391–3401 |doi=10.1210/en.2006-0845 |issn=0013-7227 |pmid=17412802}}</ref> but outcomes where the processes oppose (e.g. proportions of cell types) remain unreported ''in vitro'' as of 2025.

In primates, the developmental influence of [[androgens]] is less clear, and the consequences are less understood. Within the brain, testosterone is aromatized (to [[estradiol]]), which is the principal active hormone for developmental influences. The human [[testis]] secretes high levels of testosterone from about week eight of fetal life until five to six months after birth (a similar perinatal surge in testosterone is observed in many species), a process that appears to underlie the male phenotype. Estrogen from the maternal circulation is relatively ineffective, partly because of the high circulating levels of steroid-binding proteins in pregnancy.<ref name=jneuro/>

[[Sex steroid]]s are not the only important influences upon hypothalamic development; in particular, [[Puberty|pre-pubertal]] stress in early life (of rats) determines the capacity of the adult hypothalamus to respond to an acute stressor.<ref>{{cite journal | vauthors = Romeo RD, Bellani R, Karatsoreos IN, Chhua N, Vernov M, Conrad CD, McEwen BS | title = Stress history and pubertal development interact to shape hypothalamic–pituitary–adrenal axis plasticity | journal = Endocrinology | volume = 147 | issue = 4 | pages = 1664–74 | date = April 2006 | pmid = 16410296 | doi = 10.1210/en.2005-1432 | doi-access = free }}</ref> Unlike gonadal steroid receptors, [[glucocorticoid]] receptors are very widespread throughout the brain; in the [[paraventricular nucleus]], they mediate negative feedback control of [[Corticotropin-releasing hormone|CRF]] synthesis and secretion, but elsewhere their role is not well understood.

==Function==

===Hormone release===
[[File:Endocrine central nervous en.svg|thumbnail|[[Endocrine gland]]s in the human head and neck and their hormones]]
The hypothalamus has a central [[neuroendocrine]] function, most notably by its control of the [[anterior pituitary]], which in turn regulates various endocrine glands and organs. [[Releasing hormone]]s (also called releasing factors) are produced in hypothalamic nuclei then transported along [[axons]] to either the [[median eminence]] or the [[posterior pituitary]], where they are stored and released as needed.<ref>{{cite web|vauthors=Bowen R|title=Overview of Hypothalamic and Pituitary Hormones|url=http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/overview.html|access-date=5 October 2014|archive-date=1 March 2019|archive-url=https://web.archive.org/web/20190301174400/http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/overview.html}}</ref>

;Anterior pituitary
In the hypothalamic–adenohypophyseal axis, releasing hormones, also known as hypophysiotropic or hypothalamic hormones, are released from the median eminence, a prolongation of the hypothalamus, into the [[hypophyseal portal system]], which carries them to the anterior pituitary where they exert their regulatory functions on the secretion of adenohypophyseal hormones.<ref name=MelmedJameson>{{cite book |vauthors=Melmed S, Jameson JL |veditors=Kasper DL, Braunwald E, Fauci AS |title=Harrison's Principles of Internal Medicine|url=https://archive.org/details/harrisonsprincip00kasp |url-access=limited |edition=16th |year=2005 |publisher=McGraw-Hill |location=New York, NY |isbn=978-0-07-139140-5 |pages=[https://archive.org/details/harrisonsprincip00kasp/page/n2104 2076]–97 |chapter=Disorders of the anterior pituitary and hypothalamus|display-editors=etal}}</ref> These hypophysiotropic hormones are stimulated by parvocellular neurosecretory cells located in the periventricular area of the hypothalamus. After their release into the capillaries of the third ventricle, the hypophysiotropic hormones travel through what is known as the hypothalamo-pituitary portal circulation. Once they reach their destination in the anterior pituitary, these hormones bind to specific receptors located on the surface of pituitary cells. Depending on which cells are activated through this binding, the pituitary will either begin secreting or stop secreting hormones into the rest of the bloodstream.<ref>{{cite book | vauthors = Bear MF, Connors BW, Paradiso MA | chapter = Hypothalamic Control of the Anterior Pituitary | title = Neuroscience: Exploring the Brain |edition=4th|location=Philadelphia| publisher=Wolters Kluwer|year=2016|page=528|isbn=978-0-7817-7817-6}}</ref>

{| class="wikitable" width=100%
! width=25% | Secreted hormone !! width=6% | Abbreviation !! width=17% | Produced by !! Effect
|-
! [[Thyrotropin-releasing hormone]] <br />(Prolactin-releasing hormone)
| TRH, TRF, or PRH || [[Parvocellular neurosecretory cell]]s of the [[paraventricular nucleus]] || Stimulate [[Thyroid-stimulating hormone|thyroid-stimulating hormone (TSH)]] release from [[anterior pituitary]] (primarily) <br />Stimulate [[prolactin]] release from [[anterior pituitary]]
|-
! [[Corticotropin-releasing hormone]]
| CRH or CRF || Parvocellular neurosecretory cells of the paraventricular nucleus || Stimulate [[Adrenocorticotropic hormone|adrenocorticotropic hormone (ACTH)]] release from [[anterior pituitary]]
|-
! [[Dopamine]] <br />(Prolactin-inhibiting hormone)
| DA or PIH || [[Arcuate nucleus|Dopamine neurons of the arcuate nucleus]] || Inhibit [[prolactin]] release from [[anterior pituitary]]
|-
! [[Growth-hormone-releasing hormone]]
| GHRH || [[Neuroendocrine]] neurons of the [[Arcuate nucleus]] || Stimulate [[Growth hormone|growth-hormone (GH)]] release from [[anterior pituitary]]
|-
! [[Gonadotropin-releasing hormone]]
| GnRH or LHRH || [[Neuroendocrine]] cells of the [[Preoptic area]] || Stimulate [[Follicle-stimulating hormone|follicle-stimulating hormone (FSH)]] release from [[anterior pituitary]] <br />Stimulate [[Luteinizing hormone|luteinizing hormone (LH)]] release from [[anterior pituitary]]
|-
! [[Somatostatin]]<ref>{{cite journal | vauthors = Ben-Shlomo A, Melmed S | title = Pituitary somatostatin receptor signaling | journal = Trends in Endocrinology and Metabolism | volume = 21 | issue = 3 | pages = 123–33 | date = March 2010 | pmid = 20149677 | pmc = 2834886 | doi = 10.1016/j.tem.2009.12.003 }}</ref> <br />(growth-hormone-inhibiting hormone)
| SS, GHIH, or SRIF || [[Neuroendocrine]] cells of the [[Periventricular nucleus]] || Inhibit [[Growth hormone|growth-hormone (GH)]] release from [[anterior pituitary]] <br />Inhibit (moderately) [[Thyroid-stimulating hormone|thyroid-stimulating hormone (TSH)]] release from [[anterior pituitary]]
|}

Other hormones secreted from the median eminence include [[vasopressin]], [[oxytocin]], and [[neurotensin]].<ref name=horn>{{cite journal | vauthors = Horn AM, Robinson IC, Fink G | title = Oxytocin and vasopressin in rat hypophysial portal blood: experimental studies in normal and Brattleboro rats | journal = The Journal of Endocrinology | volume = 104 | issue = 2 | pages = 211–24 | date = February 1985 | pmid = 3968510 | doi = 10.1677/joe.0.1040211 }}</ref><ref>{{cite journal | vauthors = Date Y, Mondal MS, Matsukura S, Ueta Y, Yamashita H, Kaiya H, Kangawa K, Nakazato M | title = Distribution of orexin/hypocretin in the rat median eminence and pituitary | journal = Brain Research. Molecular Brain Research | volume = 76 | issue = 1 | pages = 1–6 | date = March 2000 | pmid = 10719209 | doi = 10.1016/s0169-328x(99)00317-4 }}</ref><ref>{{cite journal | vauthors = Watanobe H, Takebe K | title = In vivo release of neurotensin from the median eminence of ovariectomized estrogen-primed rats as estimated by push-pull perfusion: correlation with luteinizing hormone and prolactin surges | journal = Neuroendocrinology | volume = 57 | issue = 4 | pages = 760–4 | date = April 1993 | pmid = 8367038 | doi = 10.1159/000126434 }}</ref><ref>{{cite journal | vauthors = Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG | title = Orexins in the regulation of the hypothalamic–pituitary–adrenal axis | journal = Pharmacological Reviews | volume = 58 | issue = 1 | pages = 46–57 | date = March 2006 | pmid = 16507882 | doi = 10.1124/pr.58.1.4 | s2cid = 17941978 }}</ref>

;Posterior pituitary
In the hypothalamic–pituitary–adrenal axis, [[neurohypophysial hormone]]s are released from the posterior pituitary, which is actually a prolongation of the hypothalamus, into the circulation.

{| class="wikitable" width=100%
! width=25% | Secreted hormone !! width=6% | Abbreviation !! width=17% | Produced by !! Effect
|-
! [[Oxytocin]]
| OXY or OXT || [[Magnocellular neurosecretory cell]]s of the paraventricular nucleus and [[supraoptic nucleus]] || [[Uterine contraction]] <br />[[Letdown reflex|Lactation (letdown reflex)]] <!--Not effects from hypothalamus: sexual arousal, bonding, trust, material behavior-->
|-
! [[Vasopressin]] <br />(antidiuretic hormone)
| ADH or AVP || Magnocellular and parvocellular neurosecretory cells of the paraventricular nucleus, magnocellular cells in supraoptic nucleus || Increase in the permeability to water of the cells of [[distal tubule]] and [[collecting duct]] in the kidney and thus allows water reabsorption and excretion of concentrated urine
|}

It is also known that [[hypothalamic–pituitary–adrenal axis]] (HPA) hormones are related to certain skin diseases and skin homeostasis. There is evidence linking hyperactivity of HPA hormones to stress-related skin diseases and skin tumors.<ref>{{cite web|title=Expression of Hypothalamic–Pituitary–Adrenal Axis in Common Skin Diseases: Evidence of its Association with Stress-related Disease Activity|url=http://web.b.ebscohost.com/ehost/pdfviewer/pdfviewer?sid=8239d5d4-8cd4-48b0-b25c-e1218229f462%40sessionmgr115&vid=11&hid=122|publisher=National Research Foundation of Korea|access-date=4 March 2014|author1=Jung Eun Kim |author2=Baik Kee Cho |author3=Dae Ho Cho |author4=Hyun Jeong Park |year=2013}}</ref>

===Stimulation===
The hypothalamus coordinates many hormonal and behavioural circadian rhythms, complex patterns of [[neuroendocrine]] outputs, complex [[homeostasis|homeostatic]] mechanisms, and important behaviours. The hypothalamus must, therefore, respond to many different signals, some of which are generated externally and some internally. [[Delta wave]] signalling arising either in the thalamus or in the cortex influences the secretion of releasing hormones; [[GHRH]] and [[prolactin]] are stimulated whilst [[TRH]] is inhibited. {{citation needed|date=March 2025}}

The hypothalamus is responsive to:
* Light: daylength and [[photoperiod]] for regulating [[circadian]] and seasonal rhythms
* [[Olfactory]] stimuli, including [[pheromones]]
* [[Steroids]], including [[gonadal steroids]] and [[corticosteroids]]
* Neurally transmitted information arising in particular from the heart, [[enteric nervous system]] (of the [[gastrointestinal tract]]),<ref>{{cite journal | vauthors = Mayer EA | title = Gut feelings: the emerging biology of gut-brain communication | journal = Nature Reviews. Neuroscience | volume = 12 | issue = 8 | pages = 453–66 | date = July 2011 | pmid = 21750565 | pmc = 3845678 | doi = 10.1038/nrn3071 }}</ref> and the reproductive tract.{{citation needed|reason=Your explanation here|date=April 2016}}
* [[Autonomic Nervous System|Autonomic]] inputs
* Blood-borne stimuli, including [[leptin]], [[ghrelin]], [[angiotensin]], [[insulin]], [[pituitary hormones]], [[cytokines]], plasma concentrations of glucose and osmolarity etc.
* [[Stress (medicine)|Stress]]
* Invading microorganisms by increasing body temperature, resetting the body's thermostat upward.

====Olfactory stimuli====
Olfactory stimuli are important for [[sexual reproduction]] and [[neuroendocrine]] function in many species. For instance, if a pregnant mouse is exposed to the urine of a 'strange' male during a critical period after coitus then the pregnancy fails (the [[Bruce effect]]). Thus, during coitus, a female mouse forms a precise 'olfactory memory' of her partner that persists for several days. Pheromonal cues aid synchronization of [[oestrus]] in many species; in women, synchronized [[menstruation]] may also arise from pheromonal cues, although the role of pheromones in humans is disputed. {{citation needed|date=March 2025}}

====Blood-borne stimuli====
[[Peptide]] hormones have important influences upon the hypothalamus, and to do so they must pass through the [[blood–brain barrier]]. The hypothalamus is bounded in part by specialized brain regions that lack an effective blood–brain barrier; the [[Capillary#Types|capillary]] [[endothelium]] at these sites is fenestrated to allow free passage of even large proteins and other molecules. Some of these sites are the sites of neurosecretion - the [[neurohypophysis]] and the [[median eminence]]. However, others are sites at which the brain samples the composition of the blood. Two of these sites, the SFO ([[subfornical organ]]) and the OVLT ([[organum vasculosum of the lamina terminalis]]) are so-called [[circumventricular organs]], where neurons are in intimate contact with both blood and [[Cerebrospinal fluid|CSF]]. These structures are densely vascularized, and contain osmoreceptive and sodium-receptive neurons that control [[drinking]], [[vasopressin]] release, sodium excretion, and sodium appetite. They also contain neurons with receptors for [[angiotensin]], [[atrial natriuretic factor]], [[endothelin]] and [[relaxin]], each of which important in the regulation of fluid and electrolyte balance. Neurons in the OVLT and SFO project to the [[supraoptic nucleus]] and [[paraventricular nucleus]], and also to preoptic hypothalamic areas. The circumventricular organs may also be the site of action of [[interleukins]] to elicit both fever and ACTH secretion, via effects on paraventricular neurons.{{citation needed|date=February 2013}}

It is not clear how all peptides that influence hypothalamic activity gain the necessary access. In the case of [[prolactin]] and [[leptin]], there is evidence of active uptake at the [[choroid plexus]] from the blood into the [[cerebrospinal fluid]] (CSF). Some pituitary hormones have a negative feedback influence upon hypothalamic secretion; for example, [[growth hormone]] feeds back on the hypothalamus, but how it enters the brain is not clear. There is also evidence for central actions of [[prolactin]].{{citation needed|date=February 2013}}

Findings have suggested that [[thyroid hormone]] (T4) is taken up by the hypothalamic [[glial cells]] in the [[infundibular nucleus]]/ [[median eminence]], and that it is here converted into [[Triiodothyronine|T3]] by the type 2 deiodinase (D2). Subsequent to this, T3 is transported into the [[thyrotropin-releasing hormone]] ([[TRH]])-producing [[neurons]] in the [[paraventricular nucleus]]. [[Thyroid hormone receptor]]s have been found in these [[neurons]], indicating that they are indeed sensitive to T3 stimuli. In addition, these neurons expressed [[SLC16A2|MCT8]], a [[thyroid hormone]] transporter, supporting the theory that T3 is transported into them. T3 could then bind to the thyroid hormone receptor in these neurons and affect the production of thyrotropin-releasing hormone, thereby regulating thyroid hormone production.<ref>{{cite journal|vauthors=Fliers E, Unmehopa UA, Alkemade A|date=June 2006|title=Functional neuroanatomy of thyroid hormone feedback in the human hypothalamus and pituitary gland|journal=Molecular and Cellular Endocrinology|volume=251|issue=1–2|pages=1–8|doi=10.1016/j.mce.2006.03.042|pmid=16707210|s2cid=33268046}}<!--|access-date=7 July 2011--></ref>

The hypothalamus functions as a type of [[thermostat]] for the body.<ref name=Harrisons>{{cite book | author-link = Anthony Fauci | author = Fauci, Anthony | title = Harrison's Principles of Internal Medicine | url = https://archive.org/details/harrisonsprincip00asfa | url-access = limited | edition = 17 | publisher = McGraw-Hill Professional | year = 2008 | isbn = 978-0-07-146633-2 | pages = [https://archive.org/details/harrisonsprincip00asfa/page/n155 117]–121 | display-authors = etal }}</ref> It sets a desired body temperature, and stimulates either heat production and retention to raise the blood temperature to a higher setting or sweating and [[vasodilation]] to cool the blood to a lower temperature. All [[fever]]s result from a raised setting in the hypothalamus; elevated body temperatures due to any other cause are classified as [[hyperthermia]].<ref name=Harrisons /> Rarely, direct damage to the hypothalamus, such as from a [[stroke]], will cause a fever; this is sometimes called a ''hypothalamic fever''. However, it is more common for such damage to cause abnormally low body temperatures.<ref name=Harrisons />

====Steroids====
The hypothalamus contains neurons that react strongly to steroids and [[glucocorticoids]] (the steroid hormones of the [[adrenal gland]], released in response to [[ACTH]]). It also contains specialized glucose-sensitive neurons (in the [[arcuate nucleus]] and [[ventromedial hypothalamus]]), which are important for [[appetite]]. The preoptic area contains thermosensitive neurons; these are important for [[TRH]] secretion. {{citation needed|date=March 2025}}

====Neural====
[[Oxytocin]] secretion in response to suckling or vagino-cervical stimulation is mediated by some of these pathways; [[vasopressin]] secretion in response to cardiovascular stimuli arising from chemoreceptors in the [[carotid body]] and [[aortic arch]], and from low-pressure [[atrial volume receptors]], is mediated by others. In the rat, stimulation of the [[vagina]] also causes [[prolactin]] secretion, and this results in [[pseudo-pregnancy]] following an infertile mating. In the rabbit, coitus elicits [[Induced ovulation (animals)|reflex ovulation]]. In the sheep, [[cervix|cervical]] stimulation in the presence of high levels of estrogen can induce [[maternal bond|maternal behavior]] in a virgin ewe. These effects are all mediated by the hypothalamus, and the information is carried mainly by spinal pathways that relay in the brainstem. Stimulation of the nipples stimulates release of oxytocin and prolactin and suppresses the release of [[Luteinizing hormone|LH]] and [[Follicle-stimulating hormone|FSH]]. {{citation needed|date=March 2025}}

Cardiovascular stimuli are carried by the [[vagus nerve]]. The vagus also conveys a variety of visceral information, including for instance signals arising from gastric distension or emptying, to suppress or promote feeding, by signalling the release of [[leptin]] or [[gastrin]], respectively. Again, this information reaches the hypothalamus via relays in the brainstem. {{citation needed|date=March 2025}}

In addition, hypothalamic function is responsive to—and regulated by—levels of all three classical [[monoamine neurotransmitter]]s, [[noradrenaline]], [[dopamine]], and [[serotonin]] (5-hydroxytryptamine), in those tracts from which it receives innervation. For example, noradrenergic inputs arising from the locus coeruleus have important regulatory effects upon [[corticotropin-releasing hormone]] (CRH) levels. {{citation needed|date=March 2025}}

===Control of food intake===
{| class="wikitable sortable" style="width:40%; float:right; margin-left:15px"
|+ Peptide hormones and neuropeptides that regulate feeding<ref name="Feeding peptides table">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | page = 263 | edition = 2nd | chapter = Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu – Table 10:3 }}</ref>
! scope="col" style="width:50%"| Peptides that increase<br />feeding behavior
! scope="col" style="width:50%"| Peptides that decrease<br />feeding behavior
|-
| [[Ghrelin]] || [[Leptin]]
|-
| [[Neuropeptide Y]] || (α,β,γ)-[[Melanocyte-stimulating hormone]]s
|-
| [[Agouti-related peptide]] || [[Cocaine and amphetamine regulated transcript|Cocaine- and amphetamine-regulated transcript peptides]]
|-
| [[Orexin]]s (A,B) || [[Corticotropin-releasing hormone]]
|-
| [[Melanin-concentrating hormone]] || [[Cholecystokinin]]
|-
| [[Galanin]] || [[Insulin]]
|-
| || [[Glucagon-like peptide 1]]
|-
|}
The extreme [[anatomical terms of location|lateral]] part of the [[ventromedial nucleus]] of the hypothalamus is responsible for the control of [[food]] intake. Stimulation of this area causes increased food intake. Bilateral [[lesion]] of this area causes complete cessation of food intake. Medial parts of the nucleus have a controlling effect on the lateral part. Bilateral lesion of the medial part of the ventromedial nucleus causes [[hyperphagia]] and obesity of the animal. Further lesion of the lateral part of the ventromedial nucleus in the same animal produces complete cessation of food intake.

There are different hypotheses related to this regulation:<ref>{{cite journal | vauthors = Theologides A | title = Anorexia-producing intermediary metabolites | journal = The American Journal of Clinical Nutrition | volume = 29 | issue = 5 | pages = 552–8 | date = May 1976 | pmid = 178168 | doi = 10.1093/ajcn/29.5.552 | doi-access = free }}</ref>

# Lipostatic hypothesis: This hypothesis holds that [[adipose]] [[biological tissue|tissue]] produces a [[humoral immunity|humoral]] signal that is proportionate to the amount of fat and acts on the hypothalamus to decrease food intake and increase energy output. It has been evident that a [[hormone]] [[leptin]] acts on the hypothalamus to decrease food intake and increase energy output.
# Gutpeptide hypothesis: [[gastrointestinal tract|gastrointestinal]] hormones like Grp, [[glucagon]]s, [[cholecystokinin|CCK]] and others claimed to inhibit food intake. The food entering the gastrointestinal tract triggers the release of these hormones, which act on the brain to produce satiety. The brain contains both CCK-A and CCK-B receptors.
# Glucostatic hypothesis: The activity of the satiety center in the ventromedial nuclei is probably governed by the [[glucose]] utilization in the neurons. It has been postulated that when their glucose utilization is low and consequently when the arteriovenous blood glucose difference across them is low, the activity across the neurons decrease. Under these conditions, the activity of the feeding center is unchecked and the individual feels hungry. Food intake is rapidly increased by intraventricular administration of [[2-deoxy-D-glucose|2-deoxyglucose]] therefore decreasing glucose utilization in cells.
# Thermostatic hypothesis: According to this hypothesis, a decrease in body temperature below a given set-point stimulates appetite, whereas an increase above the set-point inhibits appetite.

===Fear processing===
The medial zone of hypothalamus is part of a circuitry that controls motivated behaviors, like defensive behaviors.<ref name="swanson2000">{{cite journal | vauthors = Swanson LW | title = Cerebral hemisphere regulation of motivated behavior | journal = Brain Research | volume = 886 | issue = 1–2 | pages = 113–164 | date = December 2000 | pmid = 11119693 | doi = 10.1016/S0006-8993(00)02905-X | s2cid = 10167219 }}</ref> Analyses of [[c-Fos|Fos]]-labeling showed that a series of nuclei in the "behavioral control column" is important in regulating the expression of innate and conditioned defensive behaviors.<ref name="canteras2002">{{cite journal|author=Canteras, N.S.| title=The medial hypothalamic defensive system:Hodological organization and functional implications| journal=Pharmacology Biochemistry and Behavior|volume=71| issue=3|pages=481–491|year=2002|doi=10.1016/S0091-3057(01)00685-2| pmid=11830182| s2cid=12303256}}</ref>

;Antipredatory defensive behavior

Exposure to a predator (such as a cat) elicits defensive behaviors in laboratory rodents, even when the animal has never been exposed to a cat.<ref name="ribeiro2005">{{cite journal | vauthors = Ribeiro-Barbosa ER, Canteras NS, Cezário AF, Blanchard RJ, Blanchard DC | title = An alternative experimental procedure for studying predator-related defensive responses | journal = Neuroscience and Biobehavioral Reviews | volume = 29 | issue = 8 | pages = 1255–63 | year = 2005 | pmid = 16120464 | doi = 10.1016/j.neubiorev.2005.04.006 | s2cid = 8063630 }}</ref> In the hypothalamus, this exposure causes an increase in [[c-Fos#Applications|Fos-labeled]] cells in the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial nucleus, and in the ventrolateral part of the premammillary nucleus (PMDvl).<ref name="cezario2008">{{cite journal | vauthors = Cezario AF, Ribeiro-Barbosa ER, Baldo MV, Canteras NS | title = Hypothalamic sites responding to predator threats--the role of the dorsal premammillary nucleus in unconditioned and conditioned antipredatory defensive behavior | journal = The European Journal of Neuroscience | volume = 28 | issue = 5 | pages = 1003–15 | date = September 2008 | pmid = 18691328 | doi = 10.1111/j.1460-9568.2008.06392.x | s2cid = 10073236 | doi-access = free }}</ref> The premammillary nucleus has an important role in expression of defensive behaviors towards a predator, since lesions in this nucleus abolish defensive behaviors, like freezing and flight.<ref name="cezario2008"/><ref name="blanchardpmd"/> The PMD does not modulate defensive behavior in other situations, as lesions of this nucleus had minimal effects on post-shock freezing scores.<ref name="blanchardpmd">{{cite journal|author=Blanchard, D.C.|title=Dorsal premammillary nucleus differentially modulates defensive behaviors induced by different threat stimuli in rats|journal=Neuroscience Letters|volume=345|issue=3|pages=145–148|year=2003|doi=10.1016/S0304-3940(03)00415-4|pmid=12842277|s2cid=16406187}}</ref> The PMD has important connections to the dorsal [[periaqueductal gray]], an important structure in fear expression.<ref name="canteras1992">{{cite journal | vauthors = Canteras NS, Swanson LW | title = The dorsal premammillary nucleus: an unusual component of the mammillary body | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 21 | pages = 10089–93 | date = November 1992 | pmid = 1279669 | pmc = 50283 | doi = 10.1073/pnas.89.21.10089 | bibcode = 1992PNAS...8910089C | doi-access = free }}</ref><ref name="behbehani1995">{{cite journal | vauthors = Behbehani MM | title = Functional characteristics of the midbrain periaqueductal gray | journal = Progress in Neurobiology | volume = 46 | issue = 6 | pages = 575–605 | date = August 1995 | pmid = 8545545 | doi = 10.1016/0301-0082(95)00009-K | s2cid = 24690642 }}</ref> In addition, animals display risk assessment behaviors to the environment previously associated with the cat. Fos-labeled cell analysis showed that the PMDvl is the most activated structure in the hypothalamus, and inactivation with [[muscimol]] prior to exposure to the context abolishes the defensive behavior.<ref name="cezario2008"/> Therefore, the hypothalamus, mainly the PMDvl, has an important role in expression of innate and conditioned defensive behaviors to a predator.

;Social defeat

Likewise, the hypothalamus has a role in [[social defeat]]: nuclei in medial zone are also mobilized during an encounter with an aggressive conspecific. The defeated animal has an increase in Fos levels in sexually dimorphic structures, such as the medial pre-optic nucleus, the ventrolateral part of ventromedial nucleus, and the ventral premammilary nucleus.<ref name="motta2009">{{cite journal | vauthors = Motta SC, Goto M, Gouveia FV, Baldo MV, Canteras NS, Swanson LW | title = Dissecting the brain's fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 12 | pages = 4870–5 | date = March 2009 | pmid = 19273843 | pmc = 2660765 | doi = 10.1073/pnas.0900939106 | bibcode = 2009PNAS..106.4870M | doi-access = free }}</ref> Such structures are important in other social behaviors, such as sexual and aggressive behaviors. Moreover, the premammillary nucleus also is mobilized, the dorsomedial part but not the ventrolateral part.<ref name="motta2009"/> Lesions in this nucleus abolish passive defensive behavior, like freezing and the "on-the-back" posture.<ref name="motta2009"/>

=== Learning arbitrator ===
Recent research has questioned whether the lateral hypothalamus's role is only restricted to initiating and stopping innate behaviors and argued it learns about food-related cues. Specifically, that it opposes learning about information what is neutral or distant to food. According this view, the lateral hypothalamus is "a unique arbitrator of learning capable of shifting behavior toward or away from important events".<ref name="h081">{{cite journal | vauthors = Sharpe MJ | title = The cognitive (lateral) hypothalamus | journal = Trends in Cognitive Sciences | volume = 28 | issue = 1 | pages = 18–29 | date = January 2024 | pmid = 37758590 | pmc = 10841673 | doi = 10.1016/j.tics.2023.08.019 }}</ref>

==Additional images==
<gallery>
File:Illu diencephalon.jpg
File:Human brain left dissected midsagittal view description 2.JPG|Human brain left dissected midsagittal view
File:Blausen 0536 HypothalamusLocation.png|Location of the hypothalamus
</gallery>

==See also==
* [[Ventrolateral preoptic nucleus]]
* [[Periventricular nucleus]]
* [[Copeptin]]
* [[Hypothalamic–pituitary–adrenal axis]] (HPA axis)
* [[Hypothalamic–pituitary–gonadal axis]] (HPG axis)
* [[Hypothalamic–pituitary–thyroid axis]] (HPT axis)
* [[Incertohypothalamic pathway]]
* [[Neuroendocrinology]]
* [[Neuroscience of sleep]]

== Notes ==
{{reflist|group=Note|refs=<ref name=Note01>Sex hormones are directly involved in the [[Feedback|feedback loop]] of the HPG axis.</ref>
<ref name=Note02>Sex hormones are not directly involved in the HPA axis, but nevertheless alter how the hypothalamus responds within the pathway.</ref>
}}

==References==
{{Reflist|30em}}

==Further reading==
* {{cite journal | vauthors = de Vries GJ, Södersten P | title = Sex differences in the brain: the relation between structure and function | journal = Hormones and Behavior | volume = 55 | issue = 5 | pages = 589–96 | date = May 2009 | pmid = 19446075 | pmc = 3932614 | doi = 10.1016/j.yhbeh.2009.03.012 }}

==External links==
{{wiktionary | hypothalamus}}
{{Commons category|Hypothalamus}}
* {{BrainMaps|Hypothalamus}}
* [https://web.archive.org/web/20060514115805/http://www.endotext.org/neuroendo/neuroendo3b/neuroendo3b.htm The Hypothalamus and Pituitary at endotexts.org]
* [https://web.archive.org/web/20130703215852/https://www.neuinfo.org/mynif/search.php?q=Hypothalamus&t=data&s=cover&b=0&r=20 NIF Search - Hypothalamus] via the [[Neuroscience Information Framework]]
* Space-filling and cross-sectional diagrams of hypothalamic nuclei: [http://www.netterimages.com/image/8535.htm right hypothalamus], [http://www.netterimages.com/image/8584.htm anterior], [http://www.netterimages.com/image/8586.htm tubular], [http://www.netterimages.com/image/8588.htm posterior].

{{Diencephalon}}
{{Endocrine system}}

{{Authority control}}

[[Category:Hypothalamus| ]]
[[Category:Endocrine system anatomy]]
[[Category:Limbic system]]
[[Category:Neuroendocrinology]]
[[Category:Human female endocrine system]]