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{{Short description|Hormone-producing glands of a body}}
{{Use American English|date=March 2019}}
{{Use mdy dates|date=March 2019}}
{{Infobox anatomy
| Name        = Endocrine system
| Latin       = systema endocrinum
| Image       = File:Endocrine_English.svg
| Caption     = Main [[Endocrine gland|glands]] of the human endocrine system
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The '''endocrine system'''<ref>{{Cite web |date=2019-11-19 |title=Anatomy of the Endocrine System |url=https://www.hopkinsmedicine.org/health/wellness-and-prevention/anatomy-of-the-endocrine-system |access-date=2022-06-14 |website=www.hopkinsmedicine.org |language=en}}</ref> is a messenger system in an [[organism]] comprising [[feedback loop]]s of [[hormone]]s that are released by internal [[gland]]s directly into the [[circulatory system]] and that target and regulate distant [[Organ (biology)|organs]]. In [[vertebrate]]s, the [[hypothalamus]] is the neural control center for all endocrine systems.

In [[humans]], the major [[endocrine gland]]s are the [[thyroid gland|thyroid]], [[parathyroid gland|parathyroid]], [[pituitary gland|pituitary]], [[pineal gland|pineal]], and [[adrenal gland]]s, and the (male) [[testis]] and (female) [[ovaries]]. The [[hypothalamus]], [[pancreas]], and [[thymus]] also function as endocrine glands, among other functions. (The hypothalamus and pituitary glands are organs of the [[Neuroendocrinology#Neuroendocrine system|neuroendocrine system]]. One of the most important functions of the hypothalamus{{mdash}}it is located in the [[brain]] adjacent to the pituitary gland{{mdash}}is to link the endocrine system to the [[nervous system]] via the pituitary gland.) Other organs, such as the [[kidneys]], also have roles within the endocrine system by secreting certain hormones. The study of the endocrine system and its disorders is known as [[endocrinology]].
The [[thyroid gland|thyroid]] secretes [[thyroxine]], the [[pituitary gland|pituitary]] secretes [[growth hormone]], the [[pineal gland|pineal]] secretes [[melatonin]], the testis secretes [[testosterone]], and the [[ovaries]] secrete [[estrogen]] and [[progesterone]].<ref>{{Cite book |last=Gardner, Shoback |title=Greenspan's Basic and Clinical Endocrinology |publisher=McGraw Hill / Medical |year=2017 |isbn=978-1259589287 |edition=10th |pages=49–68}}</ref>

[[Gland|Glands]] that signal each other in sequence are often referred to as an axis, such as the [[hypothalamic–pituitary–adrenal axis]]. In addition to the specialized endocrine organs mentioned above, many other organs that are part of other body systems have secondary endocrine functions, including [[bone]], [[kidney]]s, [[liver]], [[heart]] and [[gonad]]s. For example, the kidney secretes the endocrine hormone [[erythropoietin]]. Hormones can be amino acid complexes, [[steroid]]s, [[eicosanoid]]s, [[leukotriene]]s, or [[prostaglandin]]s.<ref name="Marieb" />

The endocrine system is contrasted both to [[exocrine glands]], which secrete hormones to the outside of the body, and to the system known as  [[paracrine signalling]] between cells over a relatively short distance. Endocrine glands have no [[Duct (anatomy)|ducts]], are vascular, and commonly have intracellular vacuoles or granules that store their hormones. In contrast, exocrine glands, such as [[salivary gland]]s, [[mammary gland]]s, and [[submucosal glands]] within the [[Human gastrointestinal tract|gastrointestinal tract]], tend to be much less vascular and have ducts or a hollow [[Lumen (anatomy)|lumen]].
Endocrinology is a branch of [[internal medicine]].<ref name="Marieb">{{cite book |last=Marieb |first=Elaine |name-list-style=vanc |title=Anatomy & physiology |publisher=Pearson Education, Inc |location=Glenview, IL |year=2014 |isbn=978-0-321-86158-0}}</ref>

==Structure==
===Major endocrine systems===
The human endocrine system consists of several systems that operate via [[feedback loop]]s. Several important feedback systems are mediated via the [[hypothalamus]] and pituitary.<ref>{{Cite book |title=Human Physiology: From Cells to Systems |url=https://archive.org/details/humanphysiologyf00sher |url-access=registration |author=Sherwood, L. |publisher=Wadsworth Pub Co |year=1997 |isbn=978-0-495-39184-5}}</ref>
* [[Hypothalamic–pituitary–thyroid axis|TRH – TSH – T3/T4]]
* [[Hypothalamic–pituitary–gonadal axis|GnRH – LH/FSH – sex hormones]]
* [[Hypothalamic–pituitary–adrenal axis|CRH – ACTH – cortisol]]
* [[Renin–angiotensin system|Renin – angiotensin – aldosterone]]
* [[Energy homeostasis|Leptin vs. ghrelin]]

===Glands===
{{Main|Endocrine gland}}
Endocrine glands are [[gland]]s of the endocrine system that secrete their products, [[hormone]]s, directly into interstitial spaces where they are absorbed into blood rather than through a duct. The major glands of the endocrine system include the [[pineal gland]], [[pituitary gland]], [[pancreas]], [[Ovary|ovaries]], [[Testicle|testes]], [[thyroid|thyroid gland]], [[parathyroid gland]], [[hypothalamus]] and [[adrenal gland]]s. The hypothalamus and pituitary gland are [[neuroendocrine]] [[Organ (anatomy)|organ]]s.

The hypothalamus and the anterior pituitary are two out of the three endocrine glands that are important in cell signaling. They are both part of the HPA axis which is known to play a role in cell signaling in the nervous system.

Hypothalamus: The hypothalamus is a key regulator of the autonomic nervous system. The endocrine system has three sets of endocrine outputs<ref>{{cite journal |author1=Clifford B. Saper |author2=Bradford B. Lowell |title=The Hypothalamus |journal=Current Biology |date=December 1, 2014 |volume=24 |issue=23 |pages=R1111-6 |doi=10.1016/j.cub.2014.10.023 |pmid=25465326 |s2cid=18782796 |url=https://www.cell.com/action/showPdf?pii=S0960-9822%2814%2901299-8|doi-access=free |bibcode=2014CBio...24R1111S |url-access=subscription }}</ref> which include the magnocellular system, the parvocellular system, and autonomic intervention. The magnocellular is involved in the expression of oxytocin or vasopressin. The [[Parvocellular neurosecretory cell|parvocellular]] is involved in controlling the secretion of hormones from the anterior pituitary.

[[Anterior pituitary|Anterior Pituitary]]: The main role of the anterior pituitary gland is to produce and secrete [[tropic hormone]]s.<ref>{{cite book |url=https://accessmedicine.mhmedical.com/content.aspx?bookid=507&sectionid=42540503 |title=Endocrine Physiology |publisher=McGraw Hill |year=2013 |editor-link=Patricia E. Molina |edition=4 |chapter=Chapter 3. Anterior Pituitary Gland}}</ref> Some examples of tropic hormones secreted by the anterior pituitary gland include TSH, ACTH, GH, LH, and FSH.

===Endocrine cells===
There are many types of cells that make up the endocrine system and these cells typically make up larger tissues and organs that function within and outside of the endocrine system.
* [[Hypothalamus]]
* [[Anterior pituitary|Anterior pituitary gland]]
* [[Pineal gland]]
* [[Posterior pituitary|Posterior pituitary gland]]
** The posterior pituitary gland is a section of the pituitary gland. This organ does not produce any hormone but stores and secretes hormones such as [[antidiuretic hormone]] (ADH) which is synthesized by supraoptic nucleus of hypothalamus and oxytocin which is synthesized by paraventricular nucleus of hypothalamus. ADH functions to help the body to retain water; this is important in maintaining a homeostatic balance between blood solutions and water. [[Oxytocin]] functions to induce uterine contractions, stimulate lactation, and allows for ejaculation.<ref>{{cite journal |last1=Quesada |first1=Ivan |date=2008 |title=Physiology of the pancreatic α-cell and glucagon secretion: role in glucose homeostasis and diabetes |url=https://joe.bioscientifica.com/view/journals/joe/199/1/5.xml |journal=Journal of Endocrinology |volume=199 |issue=1 |pages=5–19 |doi=10.1677/JOE-08-0290|pmid=18669612 |doi-access=free }}</ref><ref>{{cite book |title=How Does The Pancreas Work? |chapter=Physiology, Posterior Pituitary |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK526130/ |year=2021 |publisher=StatPearls |pmid=30252386 |last1=Patel |first1=H. |last2=Jessu |first2=R. |last3=Tiwari |first3=V. }}</ref>
* [[Thyroid|Thyroid gland]]
** [[Thyroid follicular cell|follicular cells]] of the thyroid gland produce and secrete [[Triiodothyronine|T<sub>3</sub>]] and [[Thyroxine|T<sub>4</sub>]] in response to elevated levels of [[Thyrotropin-releasing hormone|TRH]], produced by the [[hypothalamus]], and subsequent elevated levels of [[Thyroid-stimulating hormone|TSH]], produced by the [[Anterior pituitary|anterior pituitary gland]], which further regulates the [[Metabolism|metabolic activity]] and rate of all cells, including [[cell growth]] and [[Cellular differentiation|tissue differentiation]].
* [[Parathyroid gland]] The endocrine system can control all emotions and can control temperature.
** [[Epithelium|Epithelial]] cells of the parathyroid glands are richly supplied with blood from the [[Inferior thyroid artery|inferior]] and [[superior thyroid arteries]] and secrete [[parathyroid hormone]] (PTH). PTH acts on bone, the kidneys, and the [[Gastrointestinal tract|GI tract]] to increase [[calcium]] [[reabsorption]] and phosphate excretion. In addition, PTH stimulates the conversion of [[Vitamin D]] to its most active variant, [[1,25-dihydroxyvitamin D3|1,25-dihydroxyvitamin D<sub>3</sub>]], which further stimulates [[calcium]] absorption in the GI tract.<ref name="Marieb" />
* [[Thymus|Thymus Gland]]
* [[Adrenal gland]]s
** [[Adrenal cortex]]
** [[Adrenal medulla]]
* [[Pancreas]]
** Pancreas contain nearly 1 to 2 million [[islets of Langerhans]] (a tissue which consists cells that secrete hormones) and acini. Acini secretes digestive enzymes.{{Citation needed|date=October 2025}}
*** [[Alpha cell]]s
**** The alpha cells of the pancreas secrete hormones to maintain [[Homeostasis|homeostatic]] blood sugar. Insulin is produced and excreted to lower blood sugar to normal levels. Glucagon, another hormone produced by alpha cells, is secreted in response to low blood sugar levels; glucagon stimulates [[glycogen]] stores in the liver to release sugar into the bloodstream to raise blood sugar to normal levels.<ref>{{cite journal |last1=Patel |first1=H. |last2=Jessu |first2=R. |last3=Tiwari |first3=V. |title=Physiology, Posterior Pituitary |url=https://www.ncbi.nlm.nih.gov/books/NBK526130/ |website=NCBI |year=2020 |publisher=StatPearls|pmid=30252386 }}</ref>
*** [[Beta cell]]s
**** 60% of the cells present in [[Pancreatic islets|islet of Langerhans]] are beta cells. Beta cells secrete [[insulin]]. Along with glucagon, insulin helps in maintaining glucose levels in our body. Insulin decreases blood glucose level ( a hypoglycemic hormone) whereas glucagon increases blood glucose level.{{Citation needed|date=October 2025}}
*** [[Delta cell]]s
*** [[Pancreatic islets|F Cells]]
* [[Ovary|Ovaries]]
** [[Granulosa cell]]s
* [[Testicle|Testis]]
** [[Leydig cell]]s<ref>{{Cite web |title=Leydig cell {{!}} anatomy |url=https://www.britannica.com/science/Leydig-cell |access-date=2022-06-14 |website=Britannica |language=en}}</ref>

==Development==
{{Main|Development of the endocrine system}}
The '''fetal endocrine system''' is one of the first systems to develop during [[prenatal development]].

===Adrenal glands===
The fetal [[adrenal cortex]] can be identified within four weeks of [[gestation]]. The adrenal cortex originates from the thickening of the intermediate [[mesoderm]]. At five to six weeks of gestation, the [[mesonephros]] differentiates into a tissue known as the genital ridge. The genital ridge produces the steroidogenic cells for both the gonads and the adrenal cortex. The adrenal medulla is derived from [[Ectoderm|ectodermal cells]]. Cells that will become adrenal tissue move retroperitoneally to the upper portion of the mesonephros. At seven weeks of gestation, the adrenal cells are joined by sympathetic cells that originate from the neural crest to form the [[adrenal medulla]]. At the end of the eighth week, the adrenal glands have been encapsulated and have formed a distinct organ above the developing kidneys. At birth, the adrenal glands weigh approximately eight to nine grams (twice that of the adult adrenal glands) and are 0.5% of the total body weight. At 25 weeks, the adult [[adrenal cortex]] zone develops and is responsible for the primary synthesis of [[Steroid|steroids]] during the early postnatal weeks.

===Thyroid gland===
The [[Thyroid|thyroid gland]] develops from two different clusterings of embryonic cells. One part is from the thickening of the pharyngeal floor, which serves as the precursor of the thyroxine (T<sub>4</sub>) producing [[Follicle (anatomy)|follicular]] cells. The other part is from the caudal extensions of the fourth pharyngobranchial pouches which results in the parafollicular calcitonin-secreting cells. These two structures are apparent by 16 to 17 days of gestation. Around the 24th day of gestation, the foramen [[cecum]], a thin, flask-like [[diverticulum]] of the median [[Primordium|anlage]] develops. At approximately 24 to 32 days of gestation the median anlage develops into a [[bilobed structure]]. By 50 days of gestation, the medial and lateral anlage have fused together. At 12 weeks of gestation, the fetal thyroid is capable of storing iodine for the production of [[Thyrotropin-releasing hormone|TRH]], [[Thyroid-stimulating hormone|TSH]], and free thyroid hormone. At 20 weeks, the fetus is able to implement feedback mechanisms for the production of thyroid hormones. During fetal development, T<sub>4</sub> is the major thyroid hormone being produced while triiodothyronine (T<sub>3</sub>) and its inactive derivative, reverse T<sub>3</sub>, are not detected until the third trimester.

===Parathyroid glands===
A lateral and ventral view of an [[embryo]] showing the third (inferior) and fourth (superior) parathyroid glands during the 6th week of embryogenesis

Once the embryo reaches four weeks of gestation, the [[parathyroid gland]]s begins to develop. The human embryo forms five sets of [[endoderm]]-lined pharyngeal pouches. The third and fourth pouch are responsible for developing into the inferior and superior parathyroid glands, respectively. The third pharyngeal pouch encounters the developing thyroid gland and they migrate down to the lower poles of the thyroid lobes. The fourth pharyngeal pouch later encounters the developing thyroid gland and migrates to the upper poles of the thyroid lobes. At 14 weeks of gestation, the parathyroid glands begin to enlarge from 0.1&nbsp;mm in diameter to approximately 1 – 2&nbsp;mm at birth. The developing parathyroid glands are physiologically functional beginning in the second trimester.

Studies in [[Mouse|mice]] have shown that interfering with the [[Hox gene|HOX15]] gene can cause parathyroid gland [[aplasia]], which suggests the gene plays an important role in the development of the parathyroid gland. The genes, [[TBX1]], [[CRKL]], [[GATA3]], [[GCM2]], and [[SOX3]] have also been shown to play a crucial role in the formation of the parathyroid gland. Mutations in TBX1 and CRKL genes are correlated with [[DiGeorge syndrome]], while mutations in GATA3 have also resulted in a [[DiGeorge-like syndrome]]. Malformations in the GCM2 gene have resulted in [[hypoparathyroidism]]. Studies on SOX3 gene mutations have demonstrated that it plays a role in parathyroid development. These mutations also lead to varying degrees of hypopituitarism.

===Pancreas===
The human fetal [[pancreas]] begins to develop by the fourth week of gestation. Five weeks later, the pancreatic [[Alpha cell|alpha]] and [[beta cell]]s have begun to emerge. Reaching eight to ten weeks into development, the pancreas starts producing [[insulin]], [[glucagon]], [[somatostatin]], and [[pancreatic polypeptide]]. During the early stages of fetal development, the number of pancreatic alpha cells outnumbers the number of [[Pancreatic beta cell function|pancreatic beta cells]]. The alpha cells reach their peak in the middle stage of gestation. From the middle stage until term, the beta cells continue to increase in number until they reach an approximate 1:1 ratio with the alpha cells. The [[insulin]] concentration within the fetal pancreas is 3.6 pmol/g at seven to ten weeks, which rises to 30 pmol/g at 16–25 weeks of gestation. Near term, the insulin concentration increases to 93 pmol/g. The endocrine cells have dispersed throughout the body within 10 weeks. At 31 weeks of development, the [[islets of Langerhans]] have differentiated.

While the fetal pancreas has functional beta cells by 14 to 24 weeks of gestation, the amount of insulin that is released into the bloodstream is relatively low. In a study of pregnant women carrying fetuses in the mid-gestation and near term stages of development, the fetuses did not have an increase in plasma insulin levels in response to injections of high levels of glucose. In contrast to insulin, the fetal plasma glucagon levels are relatively high and continue to increase during development. At the mid-stage of gestation, the glucagon concentration is 6 μg/g, compared to 2 μg/g in adult humans. Just like insulin, fetal glucagon plasma levels do not change in response to an infusion of glucose. However, a study of an infusion of alanine into pregnant women was shown to increase the cord blood and maternal glucagon concentrations, demonstrating a fetal response to amino acid exposure.

As such, while the fetal pancreatic alpha and beta islet cells have fully developed and are capable of hormone synthesis during the remaining fetal maturation, the islet cells are relatively immature in their capacity to produce glucagon and insulin. This is thought to be a result of the relatively stable levels of fetal [[Blood sugar|serum glucose]] concentrations achieved via maternal transfer of glucose through the placenta. On the other hand, the stable fetal serum glucose levels could be attributed to the absence of pancreatic signaling initiated by incretins during feeding. In addition, the fetal pancreatic islets cells are unable to sufficiently produce [[Cyclic adenosine monophosphate|cAMP]] and rapidly degrade cAMP by [[phosphodiesterase]] necessary to secrete glucagon and insulin.

During fetal development, the storage of glycogen is controlled by fetal [[glucocorticoid]]s and [[Human placental lactogen|placental lactogen]]. Fetal insulin is responsible for increasing glucose uptake and [[lipogenesis]] during the stages leading up to birth. Fetal cells contain a higher amount of insulin receptors in comparison to adults cells and fetal insulin receptors are not downregulated in cases of [[hyperinsulinemia]]. In comparison, fetal haptic glucagon receptors are lowered in comparison to adult cells and the glycemic effect of glucagon is blunted. This temporary physiological change aids the increased rate of fetal development during the final trimester. Poorly managed maternal [[diabetes mellitus]] is linked to [[Large for gestational age|fetal macrosomia]], increased risk of miscarriage, and defects in fetal development. Maternal hyperglycemia is also linked to increased insulin levels and beta cell hyperplasia in the post-term infant. Children of diabetic mothers are at an increased risk for conditions such as: [[polycythemia]], [[renal vein thrombosis]], [[hypocalcemia]], [[Infant respiratory distress syndrome|respiratory distress syndrome]], [[jaundice]], [[cardiomyopathy]], [[Congenital heart defect|congenital heart disease]], and improper organ development.

===Gonads===
{{Main|Development of the gonads}}

The reproductive system begins development at four to five weeks of gestation with germ cell migration. The bipotential gonad results from the collection of the medioventral region of the [[urogenital ridge]]. At the five-week point, the developing [[Gonad|gonads]] break away from the adrenal primordium. Gonadal differentiation begins 42 days following conception.

====Male gonadal development====
For males, the [[Testicles|testes]] form at six fetal weeks and the sertoli cells begin developing by the eight week of gestation. [[SRY]], the sex-determining locus, serves to differentiate the [[Sertoli cell]]s. The Sertoli cells are the point of origin for [[anti-Müllerian hormone]]. Once synthesized, the anti-Müllerian hormone initiates the ipsilateral regression of the Müllerian tract and inhibits the development of female internal features. At 10 weeks of gestation, the Leydig cells begin to produce androgen hormones. The androgen hormone dihydrotestosterone is responsible for the development of the male external genitalia.

The testicles descend during prenatal development in a two-stage process that begins at eight weeks of gestation and continues through the middle of the third trimester. During the transabdominal stage (8 to 15 weeks of gestation), the [[Gubernaculum|gubernacular ligament]] contracts and begins to thicken. The craniosuspensory ligament begins to break down. This stage is regulated by the secretion of [[INSL3|insulin-like 3]] (INSL3), a relaxin-like factor produced by the testicles, and the INSL3 G-coupled receptor, LGR8. During the transinguinal phase (25 to 35 weeks of gestation), the testicles descend into the scrotum. This stage is regulated by androgens, the genitofemoral nerve, and calcitonin gene-related peptide. During the second and third trimester, testicular development concludes with the diminution of the fetal Leydig cells and the lengthening and coiling of the [[Seminiferous tubule|seminiferous cords]].

====Female gonadal development====
For females, the [[Ovary|ovaries]] become morphologically visible by the 8th week of gestation. The absence of testosterone results in the diminution of the Wolffian structures. The Müllerian structures remain and develop into the fallopian tubes, uterus, and the upper region of the vagina. The [[urogenital sinus]] develops into the urethra and lower region of the vagina, the genital tubercle develops into the clitoris, the urogenital folds develop into the labia minora, and the urogenital swellings develop into the labia majora. At 16 weeks of gestation, the ovaries produce [[Follicle-stimulating hormone receptor|FSH]] and [[Luteinizing hormone/choriogonadotropin receptor|LH/hCG receptors]]. At 20 weeks of gestation, the theca cell precursors are present and oogonia [[mitosis]] is occurring. At 25 weeks of gestation, the ovary is morphologically defined and [[folliculogenesis]] can begin.

Studies of [[gene expression]] show that a specific complement of genes, such as follistatin and multiple cyclin kinase inhibitors are involved in ovarian development. An assortment of genes and proteins - such as WNT4, RSPO1, FOXL2, and various estrogen receptors - have been shown to prevent the development of testicles or the lineage of male-type cells.

===Pituitary gland===
The [[pituitary gland]] is formed within the rostral neural plate. The Rathke's pouch, a cavity of ectodermal cells of the [[oropharynx]], forms between the fourth and fifth week of gestation and upon full development, it gives rise to the anterior pituitary gland. By seven weeks of gestation, the anterior pituitary vascular system begins to develop. During the first 12 weeks of gestation, the anterior pituitary undergoes cellular differentiation. At 20 weeks of gestation, the [[hypophyseal portal system]] has developed. The Rathke's pouch grows towards the third ventricle and fuses with the diverticulum. This eliminates the lumen and the structure becomes Rathke's cleft. The posterior pituitary lobe is formed from the diverticulum. Portions of the pituitary tissue may remain in the nasopharyngeal midline. In rare cases this results in functioning ectopic hormone-secreting tumors in the nasopharynx.

The functional development of the anterior pituitary involves [[spatiotemporal]] regulation of transcription factors expressed in pituitary stem cells and dynamic gradients of local soluble factors. The coordination of the dorsal gradient of pituitary morphogenesis is dependent on neuroectodermal signals from the infundibular bone morphogenetic protein 4 (BMP4). This protein is responsible for the development of the initial invagination of the Rathke's pouch. Other essential proteins necessary for pituitary cell proliferation are [[FGF8|Fibroblast growth factor 8]] (FGF8), Wnt4, and Wnt5. Ventral developmental patterning and the expression of transcription factors is influenced by the gradients of BMP2 and [[Sonic hedgehog|sonic hedgehog protein]] (SHH). These factors are essential for coordinating early patterns of cell proliferation.

Six weeks into gestation, the [[Corticotropic cell|corticotroph cells]] can be identified. By seven weeks of gestation, the anterior pituitary is capable of secreting ACTH. Within eight weeks of gestation, [[Somatotropic cell|somatotroph]] cells begin to develop with [[cytoplasmic]] expression of human growth hormone. Once a fetus reaches 12 weeks of development, the thyrotrophs begin expression of Beta subunits for TSH, while [[gonadotrophs]] being to express beta-subunits for LH and FSH. Male fetuses predominately produced LH-expressing gonadotrophs, while female fetuses produce an equal expression of LH and FSH expressing gonadotrophs. At 24 weeks of gestation, prolactin-expressing [[lactotroph]]s begin to emerge.

==Function==
{{See also|List of human endocrine organs and actions}}

===Hormones===
{{Main|Hormone}}
A [[hormone]] is any of a class of [[cell signalling|signaling molecules]] produced by cells in [[gland]]s in [[multicellular organism]]s that are transported by the [[circulatory system]] to target distant organs to regulate [[physiology]] and [[behaviour]]. Hormones have diverse chemical structures, mainly of 3 classes: [[eicosanoid]]s, [[steroid]]s, and [[amino acid]]/[[protein]] derivatives ([[amine]]s, [[peptide]]s, and [[protein]]s). The glands that secrete hormones comprise the endocrine system. The term hormone is sometimes extended to include chemicals produced by cells that affect the same cell ([[autocrine signaling|autocrine]] or [[intracrine|intracrine signalling]]) or nearby cells ([[paracrine signalling]]).

Hormones are used to communicate between [[organ (anatomy)|organs]] and tissues for [[physiological]] regulation and [[behavioral]] activities, such as digestion, [[metabolism]], [[respiration (physiology)|respiration]], [[tissue (biology)|tissue]] function, [[sensory perception]], [[sleep]], [[excretion]], [[lactation]], [[Stress (physiology)|stress]], [[human development (biology)|growth and development]], [[Motor coordination|movement]], [[reproduction]], and [[mood (psychology)|mood]].<ref>{{cite book |author=Neave N |title=Hormones and behaviour: a psychological approach |year=2008 |publisher=Cambridge Univ. Press |location=Cambridge |isbn=978-0-521-69201-4}}
* {{cite journal |author=Claire L. Gibson |title=Hormones and Behaviour: A Psychological Approach |journal=Perspectives in Biology and Medicine |type=Review |volume=53 |issue=1 |pages=152–155 |date=Winter 2010 |doi=10.1353/pbm.0.0141 |s2cid=72100830 |url=http://muse.jhu.edu/journals/pbm/summary/v053/53.1.gibson.html|url-access=subscription }}</ref><ref>{{cite web |title=Hormones |url=https://www.medlineplus.gov/hormones.html |website=MedlinePlus |publisher=U.S. National Library of Medicine}}</ref>

Hormones affect distant cells by binding to specific [[receptor (biochemistry)|receptor]] proteins in the target cell resulting in a change in cell function. This may lead to cell type-specific responses that include rapid changes to the activity of existing proteins, or slower changes in the [[gene expression|expression]] of target genes. Amino acid–based hormones ([[amines]] and [[peptide hormone|peptide or protein hormones]]) are water-soluble and act on the surface of target cells via [[signal transduction]] pathways; [[steroid hormone]]s, being lipid-soluble, move through the [[plasma membrane]]s of target cells to act within their [[cell nucleus|nuclei]].

===Cell signalling===
The typical mode of [[cell signalling]] in the endocrine system is endocrine signaling, that is, using the circulatory system to reach distant target organs. However, there are also other modes, i.e., paracrine, autocrine, and [[neuroendocrine]] signaling. Purely neurocrine signaling between [[neurons]], on the other hand, belongs completely to the [[nervous system]].

====Autocrine====
{{Main|Autocrine signalling}}
Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the cells.

====Paracrine====
{{Main|Paracrine signalling}}
Some endocrinologists and clinicians include the paracrine system as part of the endocrine system, but there is not consensus. Paracrines are slower acting, targeting cells in the same tissue or organ. An example of this is [[somatostatin]] which is released by some pancreatic cells and targets other pancreatic cells.<ref name="Marieb" />

====Juxtacrine====
{{Main|Juxtacrine signalling}}
[[Juxtacrine signalling|Juxtacrine]] signaling is a type of intercellular communication that is transmitted via oligosaccharide, lipid, or protein components of a cell membrane, and may affect either the emitting cell or the immediately adjacent cells.<ref>{{Cite book |vauthors=Gilbert F |date=2000 |chapter=Juxtacrine Signaling |title=Developmental Biology |edition=6th |location=Sunderland, MA |publisher=Sinauer Associates |isbn=0-87893-243-7 |url=https://www.ncbi.nlm.nih.gov/books/NBK10072/ |language=en}}</ref>

It occurs between adjacent cells that possess broad patches of closely opposed plasma membrane linked by transmembrane channels known as [[connexon]]s. The gap between the cells can usually be between only 2 and 4&nbsp;nm.<ref name=":0">{{cite book |title=Vander's Human Physiology: the mechanisms of body function |last=Vander |first=Arthur |name-list-style=vanc |publisher=McGraw-Hill Higher Education |year=2008 |isbn=978-0-07-304962-5 |location=Boston |pages=[https://archive.org/details/isbn_9780071283663/page/332 332–333] |url=https://archive.org/details/isbn_9780071283663/page/332}}</ref>

==Clinical significance==
===Disease===
{{Main|Endocrine diseases}}
[[Endocrine diseases|Diseases of the endocrine system]] are common,<ref>{{cite book |first1=Dennis L |last1=Kasper |first2=Tinsley Randolph |last2=Harrison |name-list-style=vanc |title=Harrison's Principles of Internal Medicine |url=https://archive.org/details/harrisonsprincip00kasp |url-access=limited |publisher=[[McGraw Hill]] |year=2005 |pages=[https://archive.org/details/harrisonsprincip00kasp/page/n2102 2074] |isbn=978-0-07-139140-5}}</ref> including conditions such as [[diabetes mellitus]], [[thyroid]] disease, and [[obesity]].
Endocrine disease is characterized by misregulated hormone release (a productive [[pituitary adenoma]]), inappropriate response to signaling ([[hypothyroidism]]), lack of a gland ([[diabetes mellitus type 1]], diminished [[erythropoiesis]] in [[chronic kidney failure]]), or structural enlargement in a critical site such as the thyroid ([[toxic multinodular goitre]]). Hypofunction of endocrine glands can occur as a result of loss of reserve, hyposecretion, [[agenesis]], atrophy, or active destruction. Hyperfunction can occur as a result of hypersecretion, loss of suppression, [[hyperplasia|hyperplastic]] or [[neoplastic]] change, or hyperstimulation.

[[Endocrinopathies]] are classified as primary, secondary, or tertiary. Primary endocrine disease inhibits the action of downstream glands. Secondary endocrine disease is indicative of a problem with the pituitary gland. Tertiary endocrine disease is associated with dysfunction of the hypothalamus and its releasing hormones.<ref>{{cite book|title=Surgical procedures and anesthetic implications: a handbook for nurse anesthesia practice |last=Macksey |first=Lynn Fitzgerald |name-list-style=vanc|date=2012|publisher=Jones & Bartlett Learning |isbn=978-0-7637-8057-9|location=Sudbury, MA|pages=479|oclc=632070527}}</ref>

As the [[Thyroid cancer|thyroid]], and hormones have been implicated in signaling distant tissues to proliferate, for example, the [[estrogen receptor]] has been shown to be involved in certain [[breast cancer]]s. Endocrine, paracrine, and autocrine signaling have all been implicated in proliferation, one of the required steps of [[oncogenesis]].<ref>{{cite journal |vauthors=Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL|title=TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia|journal=Science|volume=303|issue=5659|pages=848–51|date=February 2004 |pmid=14764882 |doi=10.1126/science.1090922|bibcode=2004Sci...303..848B|s2cid=1703215}}</ref>

Other common diseases that result from endocrine dysfunction include [[Addison's disease]], [[Cushing's disease]] and [[Graves' disease]]. Cushing's disease and Addison's disease are pathologies involving the dysfunction of the adrenal gland. Dysfunction in the adrenal gland could be due to primary or secondary factors and can result in hypercortisolism or [[hypocortisolism]]. Cushing's disease is characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands.<ref>{{cite journal |vauthors=Buliman A, Tataranu LG, Paun DL, Mirica A, Dumitrache C |title=Cushing's disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment |journal=Journal of Medicine and Life |volume=9 |issue=1 |pages=12–18 |year=2016 |pmid=27974908 |pmc=5152600}}</ref> Some clinical signs of Cushing's disease include obesity, moon face, and hirsutism.<ref name=":1">{{cite book |title=Vander's Human Physiology: the mechanisms of body function |last=Vander |first=Arthur |name-list-style=vanc |publisher=McGraw-Hill Higher Education |year=2008 |isbn=978-0-07-304962-5 |location=Boston |pages=[https://archive.org/details/isbn_9780071283663/page/345 345–347] |url=https://archive.org/details/isbn_9780071283663/page/345}}</ref> Addison's disease is an endocrine disease that results from hypocortisolism caused by adrenal gland insufficiency. Adrenal insufficiency is significant because it is correlated with decreased ability to maintain blood pressure and blood sugar, a defect that can prove to be fatal.<ref>{{cite journal |vauthors=Inder WJ, Meyer C, Hunt PJ |title=Management of hypertension and heart failure in patients with Addison's disease |journal=Clinical Endocrinology|volume=82|issue=6 |pages=789–92 |date=June 2015 |pmid=25138826|doi=10.1111/cen.12592|s2cid=13552007}}</ref>

Graves' disease involves the hyperactivity of the thyroid gland which produces the T3 and T4 hormones.<ref name=":1" /> [[Graves' disease]] effects range from excess sweating, [[fatigue]], heat intolerance and [[high blood pressure]] to swelling of the eyes that causes redness, puffiness and in rare cases reduced or double vision.<ref name=":0" />

==DALY rates==
[[File:Endocrine disorders world map - DALY - WHO2002.svg|thumb|450px|left|[[Disability-adjusted life year]] for endocrine disorders per 100,000 inhabitants in 2002.<ref>{{cite web |url=https://www.who.int/entity/healthinfo/statistics/bodgbddeathdalyestimates.xls |title=Mortality and Burden of Disease Estimates for WHO Member States in 2002 |format=xls |website=World Health Organization |year=2002}}</ref>]]

{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|No data}}
{{legend|#ffff65|Less than 80}}
{{legend|#fff200|80–160}}
{{legend|#ffdc00|160–240}}
{{legend|#ffc600|240–320}}
{{legend|#ffb000|320–400}}
{{legend|#ff9a00|400–480}}
{{legend|#ff8400|480–560}}
{{legend|#ff6e00|560–640}}
{{legend|#ff5800|640–720}}
{{legend|#ff4200|720–800}}
{{legend|#ff2c00|800–1000}}
{{legend|#cb0000|More than 1000}}
{{div col end}}


A DALY (Disability-Adjusted Life Year) is a measure that reflects the total burden of disease. It combines years of life lost (due to premature death) and years lived with disability (adjusted for the severity of the disability). The lower the DALY rates, the lower the burden of endocrine disorders in a country.<ref>{{cite web | title=Age-standardized DALYs (per 100,000 population)| website=World Health Organization (WHO) | date=1900-01-01 | url=https://www.who.int/data/gho/indicator-metadata-registry/imr-details/157 | access-date=2025-03-08}}</ref>

The map shows that large parts of Asia have lower DALY rates (pale yellow), suggesting that endocrine disorders have a relatively low impact on overall health, whereas some countries in South America and Africa (specifically Suriname and Somalia) have higher DALY rates (dark orange to red), indicating a higher disease burden from endocrine disorders.

==Other animals==
A neuroendocrine system has been observed in all [[animal]]s with a nervous system and all [[vertebrate]]s have a hypothalamus–pituitary axis.<ref>{{cite journal |vauthors=Hartenstein V |title=The neuroendocrine system of invertebrates: a developmental and evolutionary perspective |journal=The Journal of Endocrinology |volume=190 |issue=3 |pages=555–70 |date=September 2006 |pmid=17003257 |doi=10.1677/joe.1.06964 |doi-access=free}}</ref> All vertebrates have a thyroid, which in [[amphibian]]s is also crucial for transformation of larvae into adult form.<ref>{{cite journal |first1=Walton W. |last1=Dickhoff |first2=Douglas S. |last2=Darling |name-list-style=vanc |year=1983 |title=Evolution of Thyroid Function and Its Control in Lower Vertebrates |journal=American Zoologist |volume=23 |issue=3 |pages=697–707 |jstor=3882951 |doi=10.1093/icb/23.3.697|doi-access=free}}</ref><ref>{{cite journal |last=Galton |first=Valerie Anne |name-list-style=vanc |title=The Role of Thyroid Hormone in Amphibian Development |journal=Integrative and Comparative Biology |date=January 1, 1988 |volume=28 |issue=2 |pages=309–18 |jstor=3883279 |doi=10.1093/icb/28.2.309|doi-access=free}}</ref> All vertebrates have adrenal gland tissue, with mammals unique in having it organized into layers.<ref>{{cite journal |vauthors=Pohorecky LA, Wurtman RJ |title=Adrenocortical control of epinephrine synthesis |journal=Pharmacological Reviews |volume=23 |issue=1 |pages=1–35 |date=March 1971 |doi=10.1016/S0031-6997(25)06886-3 |pmid=4941407}}</ref> All vertebrates have some form of a renin–angiotensin axis, and all [[tetrapods]] have aldosterone as a primary [[mineralocorticoid]].<ref>{{cite journal |vauthors=Wilson JX |title=The renin-angiotensin system in nonmammalian vertebrates |journal=Endocrine Reviews |volume=5 |issue=1 |pages=45–61 |year=1984 |pmid=6368215 |doi=10.1210/edrv-5-1-45}}</ref><ref>{{cite journal |vauthors=Colombo L, Dalla Valle L, Fiore C, Armanini D, Belvedere P |title=Aldosterone and the conquest of land |journal=Journal of Endocrinological Investigation |volume=29 |issue=4 |pages=373–9 |date=April 2006 |pmid=16699307 |doi=10.1007/bf03344112 |s2cid=25316873}}</ref>

==Additional images==
<gallery>
Blausen_0345_EndocrineSystem_Female2.png|Female endocrine system
Blausen 0346 EndocrineSystem Male2.png|Male endocrine system
</gallery>

==See also==
{{Div col|colwidth=25em}}
* [[Endocrine disease]]
* [[Endocrinology]]
* [[List of human endocrine organs and actions]]
* [[Neuroendocrinology]]
* [[Nervous system]]
* [[Paracrine signalling]]
* [[Releasing hormone]]s
* [[Tropic hormone]]
{{Div col end}}

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

==External links==
{{Wikibooks|Human Physiology|The endocrine system}}
{{Wikibooks|Anatomy and Physiology of Animals|Endocrine System}}
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* {{Commons-inline}}

{{endocrine system}}
{{organ systems}}
{{Hormones}}
{{Authority control}}{{DEFAULTSORT:Endocrine}}
[[Category:Endocrine system| ]]
[[Category:Endocrine cells]]
[[Category:Endocrine-related cutaneous conditions]]