View source for Prolactin

{{Short description|Protein family and hormone}}
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'''Prolactin''' ('''PRL'''), also known as '''lactotropin''' and '''mammotropin''', is a [[protein]] best known for its role in enabling mammals to [[lactation|produce milk]]. It is influential in over 300 separate processes in various vertebrates, including humans.<ref name="Bole-Feysot_1998"/> Prolactin is secreted from the [[pituitary gland]] in response to eating, mating, estrogen treatment, ovulation and nursing.  It is secreted heavily in pulses in between these events. Prolactin plays an essential role in metabolism, regulation of the [[immune system]] and pancreatic development.<ref>{{cite journal | vauthors = Ben-Jonathan N, Hugo ER, Brandebourg TD, LaPensee CR | title = Focus on prolactin as a metabolic hormone | language = English | journal = Trends in Endocrinology and Metabolism | volume = 17 | issue = 3 | pages = 110–116 | date = April 2006 | pmid = 16517173 | doi = 10.1016/j.tem.2006.02.005 | s2cid = 37979194 }}</ref><ref name="auto">{{cite journal | vauthors = Ali M, Mirza L | title = Morbid Obesity Due to Prolactinoma and Significant Weight Loss After Dopamine Agonist Treatment | language = English | journal = AACE Clinical Case Reports | volume = 7 | issue = 3 | pages = 204–206 | date = 2021-05-01 | pmid = 34095489 | pmc = 8165126 | doi = 10.1016/j.aace.2021.01.004 }}</ref>

Discovered in non-human animals around 1930 by [[Oscar Riddle]]<ref name="Riddle_1935">
{{cite journal | vauthors = Bates R, Riddle O | title = The preparation of prolactin | journal = Journal of Pharmacology and Experimental Therapeutics | volume = 55 | issue = 3 | pages = 365–371 | date = November 1935 | url = http://jpet.aspetjournals.org/content/55/3/365.abstract }}</ref> and confirmed in humans in 1970 by [[Henry Friesen]],<ref name="Friesen_1970">{{cite journal | vauthors = Friesen H, Guyda H, Hardy J | title = The biosynthesis of human growth hormone and prolactin | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 31 | issue = 6 | pages = 611–24 | date = Dec 1970 | pmid = 5483096 | doi = 10.1210/jcem-31-6-611 | url = http://jcem.endojournals.org/content/31/6/611.abstract | archive-url = https://archive.today/20131111163656/http://jcem.endojournals.org/content/31/6/611.abstract | archive-date = 11 November 2013 | url-access = subscription }}</ref> prolactin is a [[peptide hormone]],  encoded by the ''PRL'' [[gene]].<ref name="pmid2567059">
{{cite journal | vauthors = Evans AM, Petersen JW, Sekhon GS, DeMars R | title = Mapping of prolactin and tumor necrosis factor-beta genes on human chromosome 6p using lymphoblastoid cell deletion mutants | journal = Somatic Cell and Molecular Genetics | volume = 15 | issue = 3 | pages = 203–13 | date = May 1989 | pmid = 2567059 | doi = 10.1007/BF01534871 | s2cid = 36302971 }}</ref>

In mammals, prolactin is associated with milk production; in fish it is thought to be related to the control of water and salt balance. Prolactin also acts in a [[cytokine]]-like manner and as an important regulator of the immune system. It has important cell cycle-related functions as a growth-, differentiating- and anti-[[apoptotic]] factor. As a growth factor, binding to cytokine-like receptors, it influences [[hematopoiesis]] and [[angiogenesis]] and is involved in the regulation of blood clotting through several pathways. The hormone acts in [[endocrine]], [[Autocrine signalling|autocrine]], and [[Paracrine signalling|paracrine]] manners through the [[prolactin receptor]] and numerous [[cytokine receptor]]s.<ref name="Bole-Feysot_1998">{{cite journal | vauthors = Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA | title = Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice | journal = Endocrine Reviews | volume = 19 | issue = 3 | pages = 225–68 | date = Jun 1998 | pmid = 9626554 | doi = 10.1210/edrv.19.3.0334 | doi-access = free }}</ref>

Pituitary prolactin secretion is regulated by endocrine neurons in the [[hypothalamus]]. The most important of these are the neurosecretory [[Tuberoinfundibular pathway|tuberoinfundibulum]] (TIDA) neurons of the [[arcuate nucleus]] that secrete [[dopamine]] (a.k.a. Prolactin Inhibitory Hormone) to act on the [[D2 receptor|D<sub>2</sub> receptor]]s of [[lactotrophs]], causing [[:wikt:inhibition|inhibition]] of prolactin secretion. [[Thyrotropin-releasing hormone]] has a [[stimulation|stimulatory]] effect on prolactin release, although prolactin is the only [[anterior pituitary]] hormone whose principal control is inhibitory.

Several variants and forms are known per species. Many fish have variants ''prolactin A'' and ''prolactin B''. Most vertebrates, including humans, also have the closely related somatolactin. In humans, 14, 16, and 22 kDa variants exist.<ref name=":0">{{Citation |last1=Mizutani |first1=Kiyohito |title=Prolactin |date=2018-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780128012383980188 |work=Reference Module in Biomedical Sciences |access-date=2024-01-10 |publisher=Elsevier |doi=10.1016/b978-0-12-801238-3.98018-8 |isbn=978-0-12-801238-3 |last2=Takai |first2=Yoshimi|url-access=subscription }}</ref>

== Function ==

=== In humans ===
Prolactin has a wide variety of effects. It stimulates the [[mammary gland]]s to produce milk ([[lactation]]): increased serum concentrations of prolactin during [[pregnancy]] cause enlargement of the mammary glands and prepare for milk production, which normally starts when levels of [[progesterone]] fall by the end of pregnancy and a suckling stimulus is present. Prolactin plays an important role in [[Maternal sensitivity|maternal behavior]].<ref name="pmid9751488">{{cite journal | vauthors = Lucas BK, Ormandy CJ, Binart N, Bridges RS, Kelly PA | title = Null mutation of the prolactin receptor gene produces a defect in maternal behavior | journal = Endocrinology | volume = 139 | issue = 10 | pages = 4102–7 | date = Oct 1998 | pmid = 9751488 | doi = 10.1210/endo.139.10.6243 | doi-access = free }}</ref>

It has been shown in rats and sheep that prolactin affects lipid synthesis differentially in mammary and adipose cells. Prolactin deficiency induced by bromocriptine increased lipogenesis and insulin responsiveness in adipocytes while decreasing them in the mammary gland.<ref name="pmid2345543">{{cite journal|vauthors=Ros M, Lobato MF, García-Ruíz JP, Moreno FJ|title=Integration of lipid metabolism in the mammary gland and adipose tissue by prolactin during lactation|journal=Molecular and Cellular Biochemistry|volume=93|issue=2|pages=185–94|date=March 1990|pmid=2345543|doi=10.1007/BF00226191 |s2cid=19824793 }}</ref>

In general, [[dopamine]] inhibits prolactin<ref name="pmid2866952">{{cite journal | vauthors = Ben-Jonathan N | title = Dopamine: a prolactin-inhibiting hormone | journal = Endocrine Reviews | volume = 6 | issue = 4 | pages = 564–89 | date = 1985 | pmid = 2866952 | doi = 10.1210/edrv-6-4-564 }}</ref> but this process has feedback mechanisms.<ref name=Freeman>{{cite journal | vauthors = Freeman ME, Kanyicska B, Lerant A, Nagy G | title = Prolactin: structure, function, and regulation of secretion | journal = Physiological Reviews | volume = 80 | issue = 4 | pages = 1523–631 | date = October 2000 | pmid = 11015620 | doi = 10.1152/physrev.2000.80.4.1523 }}</ref>

Elevated levels of prolactin decrease the levels of sex hormones—[[estrogen]] in women and [[testosterone]] in men.<ref>[http://www.mayoclinic.com/health/prolactinoma/DS00532 Prolactinoma]—[[Mayo Clinic]]</ref> The effects of mildly elevated levels of prolactin are much more variable, in women, substantially increasing or decreasing estrogen levels.

Prolactin is sometimes classified as a [[gonadotropin]]<ref name="isbn0-8053-5909-5">{{cite book |vauthors=Hoehn K, Marieb EN | title = Human Anatomy & Physiology |url=https://archive.org/details/humananatomyphys0000mari_r3o8 |url-access=registration | publisher = Pearson Benjamin Cummings | location = San Francisco | year = 2007 | isbn = 978-0-8053-5909-1 | page = 605 }}</ref> although in humans it has only a weak luteotropic effect while the effect of suppressing classical gonadotropic hormones is more important.<ref name = "MeSH">{{MeSH name|Gonadotropins}}</ref> Prolactin within the normal reference ranges can act as a weak gonadotropin, but at the same time suppresses [[gonadotropin-releasing hormone]] secretion. The exact mechanism by which it inhibits gonadotropin-releasing hormone is poorly understood. Although expression of prolactin receptors have been demonstrated in rat hypothalamus, the same has not been observed in gonadotropin-releasing hormone neurons.<ref name=Grattan_2007>{{cite journal | vauthors = Grattan DR, Jasoni CL, Liu X, Anderson GM, Herbison AE | title = Prolactin regulation of gonadotropin-releasing hormone neurons to suppress luteinizing hormone secretion in mice | journal = Endocrinology | volume = 148 | issue = 9 | pages = 4344–51 | date = Sep 2007 | pmid = 17569755 | doi = 10.1210/en.2007-0403 | doi-access = free }}</ref>  Physiologic levels of prolactin in males enhance [[luteinizing hormone]]-receptors in [[Leydig cells]], resulting in testosterone secretion, which leads to [[spermatogenesis]].<ref name="Hair_2002">{{cite journal | vauthors = Hair WM, Gubbay O, Jabbour HN, Lincoln GA | title = Prolactin receptor expression in human testis and accessory tissues: localization and function | journal = Molecular Human Reproduction | volume = 8 | issue = 7 | pages = 606–11 | date = Jul 2002 | pmid = 12087074 | doi = 10.1093/molehr/8.7.606 | doi-access = free }}</ref>

Prolactin also stimulates proliferation of [[oligodendrocyte precursor cell]]s. These cells differentiate into [[oligodendrocyte]]s, the cells responsible for the formation of [[myelin]] coatings on [[axon]]s in the [[central nervous system]].<ref name="pmid17314279">{{cite journal | vauthors = Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S | title = White matter plasticity and enhanced remyelination in the maternal CNS | journal = The Journal of Neuroscience | volume = 27 | issue = 8 | pages = 1812–23 | date = Feb 2007 | pmid = 17314279 | pmc = 6673564 | doi = 10.1523/JNEUROSCI.4441-06.2007 }}</ref>

Other actions include contributing to [[pulmonary surfactant]] synthesis of the fetal [[lung]]s at the end of the pregnancy and [[immune tolerance]] of the fetus by the maternal organism during pregnancy. Prolactin promotes [[neurogenesis]] in maternal and [[fetal]] brains.<ref name="pmid12511652">{{cite journal | vauthors = Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C, Cross JC, Weiss S | title = Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin | journal = Science | volume = 299 | issue = 5603 | pages = 117–20 | date = Jan 2003 | pmid = 12511652 | doi = 10.1126/science.1076647 | bibcode = 2003Sci...299..117S | s2cid = 38577726 }}</ref><ref name="pmid21820505">{{cite journal | vauthors = Larsen CM, Grattan DR | title = Prolactin, neurogenesis, and maternal behaviors | journal = Brain, Behavior, and Immunity | volume = 26 | issue = 2 | pages = 201–9 | date = Feb 2012 | pmid = 21820505 | doi = 10.1016/j.bbi.2011.07.233 | s2cid = 27182670 }}</ref>

In [[music psychology]], it is conjectured that prolactin may play a role in the pleasurable perception of sad music, as the levels of the hormone increase when a person feels sad, producing a consoling psychological effect.<ref name="Sad_music">{{Cite journal |last=Huron |first=David |date=2011-07-13 |title=Why is sad music pleasurable? A possible role for prolactin |url=https://journals.sagepub.com/doi/abs/10.1177/1029864911401171 |journal= Musicae Scientiae|volume=15 |issue=2|pages=146–158 |doi=10.1177/1029864911401171 |s2cid=45981792 |url-access=subscription }}</ref>

=== In other vertebrates ===

The primary function of prolactin in [[fish]] is [[osmoregulation]],<ref name="pmid16406056">{{cite journal | vauthors = Sakamoto T, McCormick SD | title = Prolactin and growth hormone in fish osmoregulation | journal = General and Comparative Endocrinology | volume = 147 | issue = 1 | pages = 24–30 | date = May 2006 | pmid = 16406056 | doi = 10.1016/j.ygcen.2005.10.008 }}</ref> i.e., controlling the movement of water and salts between the tissues of the fish and the surrounding water. Like mammals, however, prolactin in fish also has reproductive functions, including promoting sexual maturation and inducing breeding cycles, as well as brooding and parental care.<ref name="pmid23791758">{{cite journal | vauthors = Whittington CM, Wilson AB | title = The role of prolactin in fish reproduction | journal = General and Comparative Endocrinology | volume = 191 | pages = 123–36 | date = September 2013 | pmid = 23791758 | doi = 10.1016/j.ygcen.2013.05.027 | url = https://ses.library.usyd.edu.au/bitstream/2123/9291/2/GCE_PRL_in_fish_reproduction_postprint.pdf }}</ref> In the South American [[Discus (fish)|discus]], prolactin may also regulate the production of a skin secretion that provides food for larval [[Juvenile fish|fry]].<ref name="pmid19272315">{{cite journal | vauthors = Khong HK, Kuah MK, Jaya-Ram A, Shu-Chien AC | title = Prolactin receptor mRNA is upregulated in discus fish (Symphysodon aequifasciata) skin during parental phase | journal = Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology | volume = 153 | issue = 1 | pages = 18–28 | date = May 2009 | pmid = 19272315 | doi = 10.1016/j.cbpb.2009.01.005 }}</ref> An increase in brooding behaviour caused by prolactin has been reported in [[chicken|hens]].<ref name="pmid15971519">{{cite journal | vauthors = Jiang RS, Xu GY, Zhang XQ, Yang N | title = Association of polymorphisms for prolactin and prolactin receptor genes with broody traits in chickens | journal = Poultry Science  | volume = 84 | issue = 6 | pages = 839–845 | date = June 2005 | pmid = 15971519 | doi = 10.1093/ps/84.6.839 | doi-access = free }}</ref>

Prolactin and [[prolactin receptor|its receptor]] are expressed in the skin, specifically in the hair follicles, where they regulate hair growth and moulting in an [[autocrine]] fashion.<ref name="pmid12707045">{{cite journal | vauthors = Foitzik K, Krause K, Nixon AJ, Ford CA, Ohnemus U, Pearson AJ, Paus R | title = Prolactin and Its Receptor Are Expressed in Murine Hair Follicle Epithelium, Show Hair Cycle-Dependent Expression, and Induce Catagen | journal = The American Journal of Pathology | volume = 162 | issue = 5 | pages = 1611–21 | date = May 2003 | pmid = 12707045 | pmc = 1851183 | doi = 10.1016/S0002-9440(10)64295-2 }}</ref><ref name="pmid11356702">{{cite journal | vauthors = Craven AJ, Ormandy CJ, Robertson FG, Wilkins RJ, Kelly PA, Nixon AJ, Pearson AJ | title = Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice | journal = Endocrinology | volume = 142 | issue = 6 | pages = 2533–9 | date = June 2001 | pmid = 11356702 | doi = 10.1210/endo.142.6.8179 | doi-access = free }}</ref> Elevated levels of prolactin can inhibit hair growth,<ref name="pmid16507890">{{cite journal | vauthors = Foitzik K, Krause K, Conrad F, Nakamura M, Funk W, Paus R | title = Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression | journal = The American Journal of Pathology | volume = 168 | issue = 3 | pages = 748–56 | date = March 2006 | pmid = 16507890 | pmc = 1606541 | doi = 10.2353/ajpath.2006.050468 }}</ref> and knock-out [[mutation]]s in the prolactin gene cause increased hair length in cattle<ref name="pmid25519203">{{cite journal | vauthors = Littlejohn MD, Henty KM, Tiplady K, Johnson T, Harland C, Lopdell T, Sherlock RG, Li W, Lukefahr SD, Shanks BC, Garrick DJ, Snell RG, Spelman RJ, Davis SR | title = Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle | journal = Nature Communications | volume = 5 | page = 5861 | date = December 2014 | pmid = 25519203 | pmc = 4284646 | doi = 10.1038/ncomms6861 | bibcode = 2014NatCo...5.5861L }}</ref> and mice.<ref name="pmid11356702"/> Conversely, mutations in the prolactin receptor can cause reduced hair growth, resulting in the "slick" phenotype in cattle.<ref name="pmid25519203"/><ref name="pmid29527221">{{cite journal | vauthors = Porto-Neto LR, Bickhart DM, Landaeta-Hernandez AJ, Utsunomiya YT, Pagan M, Jimenez E, Hansen PJ, Dikmen S, Schroeder SG, Kim ES, Sun J, Crespo E, Amati N, Cole JB, Null DJ, Garcia JF, Reverter A, Barendse W, Sonstegard TS | title = Convergent Evolution of Slick Coat in Cattle through Truncation Mutations in the Prolactin Receptor | journal = Frontiers in Genetics | volume = 9 | page = 57 | date = February 2018 | pmid = 29527221 | pmc = 5829098 | doi = 10.3389/fgene.2018.00057 | doi-access = free }}</ref> Additionally, prolactin delays hair regrowth in mice.<ref name="pmid17088411">{{cite journal | vauthors = Craven AJ, Nixon AJ, Ashby MG, Ormandy CJ, Blazek K, Wilkins RJ, Pearson AJ | title = Prolactin delays hair regrowth in mice | journal = The Journal of Endocrinology | volume = 191 | issue = 2 | pages = 415–25 | date = Nov 2006 | pmid = 17088411 | doi = 10.1677/joe.1.06685 | doi-access = free | hdl = 10289/1353 | hdl-access = free }}</ref>

Analogous to its effects on hair growth and shedding in mammals, prolactin in birds controls the [[moulting]] of feathers,<ref name="pmid16530194">{{cite journal | vauthors = Dawson A | title = Control of molt in birds: association with prolactin and gonadal regression in starlings | journal = General and Comparative Endocrinology | volume = 147 | issue = 3 | pages = 314–22 | date = July 2006 | pmid = 16530194 | doi = 10.1016/j.ygcen.2006.02.001 }}</ref> as well as the age at onset of feathering in both turkeys and chickens.<ref name="pmid29566646">{{cite journal | vauthors = Derks MF, Herrero-Medrano JM, Crooijmans RP, Vereijken A, Long JA, Megens HJ, Groenen MA | title = Early and late feathering in turkey and chicken: same gene but different mutations | journal = Genetics Selection Evolution | volume = 50 | issue = 1 | page = 7 | date = February 2018 | pmid = 29566646 | pmc = 5863816 | doi = 10.1186/s12711-018-0380-3 | doi-access = free }}</ref> [[pigeon|Pigeons]], [[flamingo|flamingos]] and male [[emperor penguin|emperor penguins]] feed their young a cheese-like secretion from the upper digestive tract called [[crop milk]], whose production is regulated by prolactin.<ref>{{Cite journal |date=2023-06-08 |title=Spatio-temporal transcriptome dynamics coordinate rapid transition of core crop functions in 'lactating' pigeon |journal=PLOS Genetics |language=en |volume=19 |issue=6 |article-number=e1010746 |doi=10.1371/journal.pgen.1010746 |doi-access=free |issn=1553-7404 |last1=Wang |first1=Yujie |last2=Wang |first2=Xun |last3=Luo |first3=Yi |last4=Zhang |first4=Jiaman |last5=Lin |first5=Yu |last6=Wu |first6=Jie |last7=Zeng |first7=Bo |last8=Liu |first8=Lei |last9=Yan |first9=Peiqi |last10=Liang |first10=Jiyuan |last11=Guo |first11=Hongrui |last12=Jin |first12=Long |last13=Tang |first13=Qianzi |last14=Long |first14=Keren |last15=Li |first15=Mingzhou |pmid=37289658 |pmc=10249823 }}</ref><ref name=":1">{{Cite journal |last1=Stewart |first1=Calum |last2=Marshall |first2=Christopher J. |date=2022 |title=Seasonality of prolactin in birds and mammals |journal=Journal of Experimental Zoology Part A: Ecological and Integrative Physiology |language=en |volume=337 |issue=9–10 |pages=919–938 |doi=10.1002/jez.2634 |issn=2471-5638 |pmc=9796654 |pmid=35686456|bibcode=2022JEZA..337..919S }}</ref>

In rodents, [[pseudopregnancy]] can occur when a female is mated with a sterile male. This mating can cause bi-daily surges of prolactin which would normally occur in rodent pregnancy.<ref>{{cite journal | vauthors = Ladyman SR, Hackwell EC, Brown RS | title = The role of prolactin in co-ordinating fertility and metabolic adaptations during reproduction | journal = Neuropharmacology | volume = 167 | article-number = 107911 | date = May 2020 | pmid = 32058177 | doi = 10.1016/j.neuropharm.2019.107911 | s2cid = 208985116 }}</ref> Prolactin surges initiate the secretion of progesterone which maintains pregnancy and hence can initiate pseudopregnancy. The false maintenance of pregnancy exhibits the outward physical symptoms of pregnancy, in the absence of a foetus.<ref>{{Cite journal | vauthors = Demirel MA, Suntar I, Ceribaşı S, Zengin G, Ceribaşı AO |date=2018-08-01 |title=Evaluation of the therapeutic effects of Artemisia absinthium L. on pseudopregnancy model in rats |journal=Phytochemistry Reviews |language=en |volume=17 |issue=4 |pages=937–946 |doi=10.1007/s11101-018-9571-3 |bibcode=2018PChRv..17..937D |s2cid=4953983 |issn=1572-980X}}</ref>

Prolactin receptor activation is essential for normal [[mammary gland]] development during [[puberty]] in mice.<ref name="pmid10935023">{{cite journal | vauthors = Ormandy CJ, Binart N, Kelly PA | title = Mammary gland development in prolactin receptor knockout mice | journal = J Mammary Gland Biol Neoplasia | volume = 2 | issue = 4 | pages = 355–64 | date = October 1997 | pmid = 10935023 | doi = 10.1023/a:1026395229025 | s2cid = 24217896 | url = }}</ref> Adult virgin female prolactin receptor [[knockout mice]] have much smaller and less developed mammary glands than their [[wild-type]] counterparts.<ref name="pmid10935023" /> Prolactin and prolactin receptor signaling are also essential for maturation of the mammary glands during pregnancy in mice.<ref name="pmid10935023" />

== Regulation ==
In humans, prolactin is produced at least in the anterior pituitary, [[decidua]], [[myometrium]], breast, [[lymphocytes]], [[leukocytes]] and [[prostate]].<ref name="Ben-Jonathan_1996">{{cite journal | vauthors = Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW | title = Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects | journal = Endocrine Reviews | volume = 17 | issue = 6 | pages = 639–69 | date = Dec 1996 | pmid = 8969972 | doi = 10.1210/edrv-17-6-639 | doi-access = free }}</ref><ref name="Gerlo_2006">{{cite journal | vauthors = Gerlo S, Davis JR, Mager DL, Kooijman R | title = Prolactin in man: a tale of two promoters | journal = BioEssays | volume = 28 | issue = 10| pages = 1051–5 | date = Oct 2006 | pmid = 16998840 | pmc = 1891148 | doi = 10.1002/bies.20468 }}</ref>

=== Pituitary ===

Pituitary prolactin is controlled by the [[Pit-1]] [[transcription factor]], which binds to the gene at several sites including a proximal promoter.<ref name="Gerlo_2006" /> This promoter is inhibited by dopamine and stimulated by estrogens, neuropeptides, and growth factors.<ref>Ben-Jonathan N. (2001) Hypothalamic control of prolactin synthesis and secretion . In: Horseman ND, ed. Prolactin. Boston: Kluwer; 1 –24</ref> Estrogens can also suppress dopamine.

Interaction with neuropeptides is still a matter of active research: no specific [[prolactin-releasing hormone]] has been identified. It is known that mice react to both [[Vasoactive intestinal peptide|VIP]] and [[thyrotropin-releasing hormone|TRH]], but humans seem to only react to TRH. There are [[prolactin-releasing peptide]]s that work ''in vitro'', but whether they deserve their name has been questioned. [[Oxytocin]] does not play a large role. Mice without a posterior pituitary do not raise their prolactin levels even with suckling and oxytocin injection, but scientists have yet to identify which specific hormone produced by this region is responsible.<ref name=pmid18057139>{{cite journal |last1=Ben-Jonathan |first1=Nira |last2=LaPensee |first2=Christopher R. |last3=LaPensee |first3=Elizabeth W. |title=What can we learn from rodents about prolactin in humans? |url=18057139 |journal=Endocrine Reviews |pages=1–41 |doi=10.1210/er.2007-0017 |date=February 2008|volume=29 |issue=1 |pmid=18057139 |pmc=2244934 }}</ref>

In birds (turkeys), VIP is a powerful prolactin-releasing factor, while [[peptide histidine isoleucine]] has almost no effect.<ref>{{cite journal | vauthors = Kulick RS, Chaiseha Y, Kang SW, Rozenboim I, El Halawani ME | title = The relative importance of vasoactive intestinal peptide and peptide histidine isoleucine as physiological regulators of prolactin in the domestic turkey | journal = General and Comparative Endocrinology | volume = 142 | issue = 3 | pages = 267–73 | date = Jul 2005 | pmid = 15935152 | doi = 10.1016/j.ygcen.2004.12.024 }}</ref>

=== Extrapituitary ===
Extrapituitary prolactin is controlled by a superdistal promoter, located 5.8 kb upstream of the pituitary start site. The promoter does not react to dopamine, estrogens, or TRH. Instead, it is stimulated by [[Cyclic adenosine monophosphate|cAMP]]. Responsiveness to cAMP is mediated by an imperfect cAMP–responsive element and two CAAT/enhancer binding proteins (C/EBP).<ref name="Gerlo_2006" /> [[Progesterone]] upregulates prolactin synthesis in the [[endometrium]] but decreases it in [[myometrium]] and breast glandular tissue.<ref name=Zinger_2003>{{cite journal | vauthors = Zinger M, McFarland M, Ben-Jonathan N | title = Prolactin expression and secretion by human breast glandular and adipose tissue explants | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 2 | pages = 689–96 | date = Feb 2003 | pmid = 12574200 | doi = 10.1210/jc.2002-021255 | doi-access = free }}</ref>

Breast and other tissues may express the Pit-1 promoter in addition to the distal promoter. [[Oct-1]] appears able to substitute for Pit-1 in activating the promoter in breast cancer cells.<ref name=pmid18057139/>

Extrapituitary production of prolactin is thought to be special to humans and primates and may serve mostly tissue-specific [[paracrine]] and [[autocrine]] purposes. It has been hypothesized that in vertebrates such as mice a similar tissue-specific effect is achieved by a large family of prolactin-like proteins controlled by at least 26 paralogous ''PRL'' genes not present in primates.<ref name="Gerlo_2006" />

=== Stimuli ===<!-- higher than molecular-level things -->
Prolactin follows [[Day|diurnal]] and [[ovulation|ovulatory]] cycles. Prolactin levels peak during REM sleep and in the early morning. Many mammals experience a seasonal cycle.<ref name=":1" />

During [[pregnancy]], high circulating concentrations of estrogen and progesterone increase prolactin levels by 10- to 20-fold. Estrogen and progesterone inhibit the stimulatory effects of prolactin on milk production. The abrupt drop of estrogen and progesterone levels following delivery allow prolactin—which temporarily remains high—to induce lactation.<ref>{{Cite journal |last1=Calik-Ksepka |first1=Anna |last2=Stradczuk |first2=Monika |last3=Czarnecka |first3=Karolina |last4=Grymowicz |first4=Monika |last5=Smolarczyk |first5=Roman |date=2022-01-31 |title=Lactational Amenorrhea: Neuroendocrine Pathways Controlling Fertility and Bone Turnover |journal=International Journal of Molecular Sciences |volume=23 |issue=3 |page=1633 |doi=10.3390/ijms23031633 |doi-access=free |issn=1422-0067 |pmc=8835773 |pmid=35163554}}</ref>

Sucking on the nipple offsets the fall in prolactin as the internal stimulus for them is removed. The sucking activates mechanoreceptors in and around the nipple. These signals are carried by nerve fibers through the spinal cord to the [[hypothalamus]], where changes in the electrical activity of neurons that regulate the [[pituitary gland]] increase prolactin secretion. The suckling stimulus also triggers the release of [[oxytocin]] from the [[posterior pituitary gland]], which triggers milk let-down: Prolactin controls milk production (lactogenesis) but not the milk-ejection reflex; the rise in prolactin fills the breast with milk in preparation for the next feed. The posterior pituitary produces a yet-unidentified hormone that causes prolactin production.<ref name=pmid18057139/>

In usual circumstances, in the absence of [[galactorrhea]], lactation ceases within one or two weeks following the end of [[breastfeeding]].

Levels can rise after exercise, high-protein meals, minor surgical procedures,<ref>{{cite book |vauthors=Melmed S, Jameson JL |chapter=333 Disorders of the Anterior Pituitary and Hypothalamus |veditors=Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL |title=Harrison's principles of internal medicine |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2005 |edition=16th |isbn=978-0-07-140235-4 |chapter-url=http://highered.mcgraw-hill.com/sites/0071402357/information_center_view0/}}</ref> following [[epileptic seizures]]<ref name="Mellors">{{cite journal | vauthors = Mellers JD | title = The approach to patients with "non-epileptic seizures" | journal = Postgraduate Medical Journal | volume = 81 | issue = 958 | pages = 498–504 | date = Aug 2005 | pmid = 16085740 | pmc = 1743326 | doi = 10.1136/pgmj.2004.029785 }}</ref> or due to physical or emotional [[Stress (psychological)|stress]].<ref name="medlineplus">{{cite news|url=https://www.medlineplus.gov/ency/article/003718.htm|title=Prolactin|publisher=MedLine plus|access-date=2014-10-24}}</ref><ref name="sobrinho-2003">{{cite journal | vauthors = Sobrinho LG | title = Prolactin, psychological stress and environment in humans: adaptation and maladaptation | journal = Pituitary | volume = 6 | issue = 1 | pages = 35–9 | year = 2003 | pmid = 14674722 | doi = 10.1023/A:1026229810876 | s2cid = 1335211 }}</ref> In a study on female volunteers under hypnosis, prolactin surges resulted from the evocation, with rage, of humiliating experiences, but not from the fantasy of nursing.<ref name="sobrinho-2003" /> Stress-induced PRL changes are not linked to the posterior pituitary in rodents.<ref name=pmid18057139/>

Hypersecretion is more common than hyposecretion. Hyperprolactinemia is the most frequent abnormality of the anterior pituitary tumors, termed [[prolactinoma]]s. Prolactinomas may disrupt the [[hypothalamic-pituitary-gonadal axis]] as prolactin tends to suppress the secretion of gonadotropin-releasing hormone from the hypothalamus and in turn decreases the secretion of [[follicle-stimulating hormone]] and [[luteinizing hormone]] from the anterior pituitary, therefore disrupting the [[Menstrual cycle|ovulatory cycle]].<ref>{{cite web | vauthors = Welt CK, Barbieri RL, Geffner ME | location = Waltham, MA | work = UpToDate | date = 2020 |title=Etiology, diagnosis, and treatment of secondary amenorrhea |url= http://www.uptodate.com/contents/etiology-diagnosis-and-treatment-of-secondary-amenorrhea?detectedLanguage=en&source=search_result&search=etiology+of+secondary+amenorrhea&selectedTitle=1%7E30&provider=noProvider |access-date=7 November 2013}}</ref> Such hormonal changes may manifest as [[amenorrhea]] and infertility in females as well as [[erectile dysfunction]] in males.<ref>{{cite journal | vauthors = Saleem M, Martin H, Coates P | title = Prolactin Biology and Laboratory Measurement: An Update on Physiology and Current Analytical Issues | journal = The Clinical Biochemist. Reviews | volume = 39 | issue = 1 | pages = 3–16 | date = February 2018 | pmid = 30072818 | pmc = 6069739 }}</ref><ref name="auto"/> Inappropriate lactation ([[Galactorrhea|galactorrhoea]]) is another important clinical sign of prolactinomas.

== Structure and isoforms ==

The structure of prolactin is similar to that of [[growth hormone]] and [[placental lactogen]]. The molecule is folded due to the activity of three [[disulfide bond]]s. Significant heterogeneity of the molecule has been described, thus [[bioassay]]s and [[immunoassay]]s can give different results due to differing [[glycosylation]], [[phosphorylation]] and [[sulfation]], as well as degradation. The non-glycosylated form of prolactin is the dominant form that is secreted by the [[pituitary gland]].<ref name=":0" />

The three different sizes of prolactin are:
* Little prolactin—the predominant form.<ref name="Sabharwal_1992">{{cite journal | vauthors = Sabharwal P, Glaser R, Lafuse W, Varma S, Liu Q, Arkins S, Kooijman R, Kutz L, Kelley KW, Malarkey WB | title = Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 16 | pages = 7713–6 | date = Aug 1992 | pmid = 1502189 | pmc = 49781 | doi = 10.1073/pnas.89.16.7713 | bibcode = 1992PNAS...89.7713S | doi-access = free }}, in turn citing: {{cite journal | vauthors = Kiefer KA, Malarkey WB | title = Size heterogeneity of human prolactin in CSF and serum: experimental conditions that alter gel filtration patterns | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 46 | issue = 1 | pages = 119–24 | date = Jan 1978 | pmid = 752015 | doi = 10.1210/jcem-46-1-119 }}</ref> It has a [[molecular weight]] of approximately 23-[[kilodalton|kDa]].<ref name="Sabharwal_1992"/> It is a single-chain [[polypeptide]] of 199 [[amino acid]]s and is apparently the result of removal of some amino acids.
* Big prolactin—approximately 48 kDa.<ref name="Sabharwal_1992"/> It may be the product of interaction of several prolactin molecules. It appears to have little, if any, biological activity.<ref name=Garnier1978>{{cite journal | vauthors = Garnier PE, Aubert ML, Kaplan SL, Grumbach MM | title = Heterogeneity of pituitary and plasma prolactin in man: decreased affinity of "Big" prolactin in a radioreceptor assay and evidence for its secretion | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 47 | issue = 6 | pages = 1273–81 | date = Dec 1978 | pmid = 263349 | doi = 10.1210/jcem-47-6-1273 }}</ref>
* [[Macroprolactin]]—approximately 150 kDa.<ref name="Sabharwal_1992"/> It appears to have a low biological activity.<ref name="pmid1483294">{{cite journal | vauthors = Leite V, Cosby H, Sobrinho LG, Fresnoza MA, Santos MA, Friesen HG | title = Characterization of big, big prolactin in patients with hyperprolactinaemia | journal = Clinical Endocrinology | volume = 37 | issue = 4 | pages = 365–72 | date = Oct 1992 | pmid = 1483294 | doi = 10.1111/j.1365-2265.1992.tb02340.x | s2cid = 42796831 }}</ref>
* Other variants with the molecular masses of 14, 16, and 22 kDa.<ref name=":0" />
The levels of larger ones are somewhat higher during the early [[postpartum period]].<ref name="pmid8291454">{{cite journal | vauthors = Kamel MA, Neulen J, Sayed GH, Salem HT, Breckwoldt M | title = Heterogeneity of human prolactin levels in serum during the early postpartum period | journal = Gynecological Endocrinology | volume = 7 | issue = 3 | pages = 173–7 | date = Sep 1993 | pmid = 8291454 | doi = 10.3109/09513599309152499 }}</ref>

== Prolactin receptor ==
{{Main|Prolactin receptor}}

Prolactin receptors are present in the [[Mammillary body|mammillary glands]], [[Ovary|ovaries]], pituitary glands, heart, lung, [[thymus]], [[spleen]], liver, pancreas, [[kidney]], [[adrenal gland]], [[uterus]], [[skeletal muscle]], skin and areas of the [[central nervous system]].<ref name=Mancini2008>{{cite journal | vauthors = Mancini T, Casanueva FF, Giustina A | title = Hyperprolactinemia and prolactinomas | journal = Endocrinology and Metabolism Clinics of North America | volume = 37 | issue = 1 | pages = 67–99, viii | date = Mar 2008 | pmid = 18226731 | doi = 10.1016/j.ecl.2007.10.013 }}</ref> When prolactin binds to the receptor, it causes it to [[Dimer (chemistry)|dimerize]] with another prolactin receptor. This results in the activation of [[Janus kinase 2]], a [[tyrosine kinase]] that initiates the [[JAK-STAT pathway]]. Activation also results in the activation of [[mitogen-activated protein kinases]] and [[Src kinase]].<ref name=Mancini2008/>

Human prolactin receptors are insensitive to mouse prolactin.<ref name="pmid16522738">{{cite journal | vauthors = Utama FE, LeBaron MJ, Neilson LM, Sultan AS, Parlow AF, Wagner KU, Rui H | title = Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice | journal = The Journal of Endocrinology | volume = 188 | issue = 3 | pages = 589–601 | date = Mar 2006 | pmid = 16522738 | doi = 10.1677/joe.1.06560 | doi-access = free }}</ref>

== Diagnostic use ==
Prolactin levels may be checked as part of a [[sex hormone]] workup, as elevated prolactin secretion can suppress the secretion of follicle stimulating hormone and gonadotropin-releasing hormone, leading to [[hypogonadism]] and sometimes causing [[erectile dysfunction]].<ref>{{Citation |last1=Al-Chalabi |first1=Mustafa |title=Physiology, Prolactin |date=2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK507829/ |work=StatPearls |access-date=2024-01-10 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29939606 |last2=Bass |first2=Autumn N. |last3=Alsalman |first3=Ihsan}}</ref>

Prolactin levels may be of some use in distinguishing [[seizure|epileptic seizures]] from [[psychogenic non-epileptic seizures]]. The serum prolactin level usually rises following an epileptic seizure.<ref>{{cite journal | vauthors = Banerjee S, Paul P, Talib VJ | title = Serum prolactin in seizure disorders | journal = Indian Pediatrics | volume = 41 | issue = 8 | pages = 827–31 | date = Aug 2004 | pmid = 15347871 }}</ref>

== Units and unit conversions ==

The serum concentration of prolactin can be given in [[mass concentration (chemistry)|mass concentration]] ([[microgram|μg]]/[[litre|L]] or [[nanogram|ng]]/[[millilitre|mL]]), [[molar concentration]] ([[nanomole|nmol]]/L or [[picomole|pmol]]/L), or [[international unit]]s (typically mIU/L). The current IU is calibrated against the third International Standard for Prolactin, IS 84/500.<ref name="Schulster 1989">{{cite journal | vauthors = Schulster D, Gaines Das RE, Jeffcoate SL | title = International Standards for human prolactin: calibration by international collaborative study | journal = The Journal of Endocrinology | volume = 121 | issue = 1 | pages = 157–66 | date = Apr 1989 | pmid = 2715755 | doi = 10.1677/joe.0.1210157 }}</ref><ref name="urlwhqlibdoc.who.int">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_786.pdf | title = WHO Expert Committee on Biological Standardization | year = 1989 | work = Thirty-ninth Report, WHO Technical Report Series | publisher = World Health Organization | quote = 86.1520, WHO/BS documents: 86.1520 Add 1, 88.1596 | access-date = 2009-06-03}}</ref> Reference ampoules of IS 84/500 contain "approximately" 2.5&nbsp;μg of [[lyophilize]]d human prolactin<ref name="NIBSC instructions">{{cite web | url = http://www.nibsc.ac.uk/documents/ifu/84-500.pdf | title = WHO International Standard, Prolactin, Human. NIBSC code: 84/500, Instructions for use | year = 1989 | publisher = NIBSC / Health Protection Agency | archive-url =https://web.archive.org/web/20111003214114/http://www.nibsc.ac.uk/documents/ifu/84-500.pdf| archive-date =2011-10-03| access-date = 2011-03-21}}</ref> and have been assigned an activity of 0.053 International Units by calibrating against the previous standard.<ref name="Schulster 1989" /><ref name="urlwhqlibdoc.who.int" /> Measurements can be converted into mass units using this ratio of grams to IUs to obtain an equivalent in relationship to the contents of IS 84/500;<ref name="CSCC 1992">{{cite journal | author = Canadian Society of Clinical Chemists | title = Canadian Society of Clinical Chemists position paper: standardization of selected polypeptide hormone measurements | journal = Clinical Biochemistry | volume = 25 | issue = 6 | pages = 415–24 | date = Dec 1992 | pmid = 1477965 | doi = 10.1016/0009-9120(92)90030-V }}</ref> prolactin concentrations expressed in mIU/L can be converted to μg/L of IS 84/500 equivalent by dividing by 21.2. Previous standards had other ratios in relation to their potency on the assay measurement. For example, the previous IS (83/562) had a potency of 27.0 mIU per μg.<ref name="Gaines Das 1979">{{cite journal | vauthors = Gaines Das RE, Cotes PM | title = International Reference Preparation of human prolactin for immunoassay: definition of the International Unit, report of a collaborative study and comparison of estimates of human prolactin made in various laboratories | journal = The Journal of Endocrinology | volume = 80 | issue = 1 | pages = 157–68 | date = Jan 1979 | pmid = 429949 | doi = 10.1677/joe.0.0800157 }}</ref><ref name="second IRP">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_725.pdf | title = WHO Expert Committee on Biological Standardization | year = 1985 | work = Thirty-fifth Report, WHO Technical Report Series | publisher = World Health Organization | access-date = 2011-03-21}}</ref><ref name="second IS">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_760.pdf | title = WHO Expert Committee on Biological Standardization | year = 1987 | work = Thirty-seventh Report, WHO Technical Report Series | publisher = World Health Organization | access-date = 2011-03-21}}{{dead link|date=December 2021|bot=medic}}{{cbignore|bot=medic}}</ref><ref name=who1963>{{cite journal | vauthors = Bangham DR, Mussett MV, Stack-Dunne MP | journal = Bulletin of the World Health Organization | volume = 29 | issue = 6 | pages = 721–8 | year = 1963 | pmid = 14107744 | pmc = 2555104 | title = The Second International Standard for Prolactin }}</ref>

The first [[International unit#Equality and equivalency of IU for different substances|International Reference Preparation]] (or IRP) of human Prolactin for Immunoassay was established in 1978 (75/504 1st IRP for human prolactin) at a time when purified human prolactin was in short supply.<ref name="CSCC 1992" /><ref name="Gaines Das 1979" /> Previous standards relied on prolactin from animal sources.<ref name=who1963 /> Purified human prolactin was scarce, heterogeneous, unstable, and difficult to characterize. A preparation labeled 81/541 was distributed by the [[WHO Expert Committee on Biological Standardization]] without official status and given the assigned value of 50 mIU/ampoule based on an earlier collaborative study.<ref name="CSCC 1992" /><ref name="second IRP" /> It was determined that this preparation behaved anomalously in certain [[immunoassays]] and was not suitable as an IS.<ref name="CSCC 1992" />

Three different human pituitary extracts containing prolactin were subsequently obtained as candidates for an IS. These were distributed into ampoules coded 83/562, 83/573, and 84/500.<ref name="Schulster 1989" /><ref name="urlwhqlibdoc.who.int" /><ref name="CSCC 1992" /><ref name="second IS" /> Collaborative studies involving 20 different laboratories found little difference between these three preparations. 83/562 appeared to be the most stable. This preparation was largely free of dimers and [[polymer]]s of prolactin. On the basis of these investigations, 83/562 was established as the Second IS for human prolactin.<ref name="second IS" /> Once stocks of these ampoules were depleted, 84/500 was established as the Third IS for human prolactin.<ref name="Schulster 1989" /><ref name="CSCC 1992" />

84/500 has nearly run out and in 2016 replacement was proposed. The new 83/573 contains 67.2&nbsp;mIU per ampoule when calibrated against the third IS and contains 1.002&nbsp;g of human pituitary extract each (which is then lyophilized). Each ampoule contains approximately 3.2&nbsp;μg of prolactin. The ''assigned value'' will be 67&nbsp;mIU per ampoule. If a fifth IS is needed, it will likely be based on [[recombinant protein]], as WHO has not received any further donations of human pituitary extracts.<ref>{{cite web |last1=Ferguson |first1=Jackie |title=WHO International Collaborative Study of the Proposed 4th International Standard for Prolactin, Human |date=2016 |url=https://www.who.int/publications/m/item/WHO-BS-2016.2292}}</ref>

== Reference ranges ==
General guidelines for diagnosing prolactin excess ([[hyperprolactinemia]]) define the upper threshold of normal prolactin at 25&nbsp;μg/L for women and 20&nbsp;μg/L for men.<ref name="Mancini2008" /> Similarly, guidelines for diagnosing prolactin deficiency ([[hypoprolactinemia]]) are defined as prolactin levels below 3&nbsp;μg/L in women<ref name="Kauppila 1988">{{cite journal | vauthors = Kauppila A, Martikainen H, Puistola U, Reinilä M, Rönnberg L | title = Hypoprolactinemia and ovarian function | journal = Fertility and Sterility | volume = 49 | issue = 3 | pages = 437–41 | date = Mar 1988 | pmid = 3342895 | doi=10.1016/s0015-0282(16)59769-6| doi-access =  }}</ref><ref name="Schwarzler 1997">{{cite journal | vauthors = Schwärzler P, Untergasser G, Hermann M, Dirnhofer S, Abendstein B, Berger P | title = Prolactin gene expression and prolactin protein in premenopausal and postmenopausal human ovaries | journal = Fertility and Sterility | volume = 68 | issue = 4 | pages = 696–701 | date = Oct 1997 | pmid = 9341613 | doi = 10.1016/S0015-0282(97)00320-8 | doi-access = free }}</ref> and 5&nbsp;μg/L in men.<ref name="Corona 2009">{{cite journal |author3-link=Emmanuele A. Jannini | vauthors = Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, Boddi V, Bandini E, Balercia G, Forti G, Maggi M | title = Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction | journal = The Journal of Sexual Medicine | volume = 6 | issue = 5 | pages = 1457–66 | date = May 2009 | pmid = 19210705 | doi = 10.1111/j.1743-6109.2008.01206.x }}</ref><ref name="Gonzales 1989">{{cite journal | vauthors = Gonzales GF, Velasquez G, Garcia-Hjarles M | title = Hypoprolactinemia as related to seminal quality and serum testosterone | journal = Archives of Andrology | volume = 23 | issue = 3 | pages = 259–65 | year = 1989 | pmid = 2619414 | doi = 10.3109/01485018908986849 }}</ref><ref name="Ufearo 1995">{{cite journal | vauthors = Ufearo CS, Orisakwe OE | title = Restoration of normal sperm characteristics in hypoprolactinemic infertile men treated with metoclopramide and exogenous human prolactin | journal = Clinical Pharmacology and Therapeutics | volume = 58 | issue = 3 | pages = 354–9 | date = Sep 1995 | pmid = 7554710 | doi = 10.1016/0009-9236(95)90253-8 | s2cid = 1735908 }}</ref> However, different assays and methods for measuring prolactin are employed by different laboratories and as such the [[Reference ranges for blood tests|serum reference range]] for prolactin is often determined by the laboratory performing the measurement.<ref name="Mancini2008" /><ref name="Beltran_2008"/> Furthermore, prolactin levels vary according to factors as age,<ref name=immulite/> sex,<ref name=immulite/> [[menstrual cycle]] stage<ref name=immulite/> and pregnancy.<ref name=immulite>[http://www.medical.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/referenzwerte_pdf/IMMULITE_Systeme/prolaktin.pdf Prolaktin] {{webarchive|url=https://web.archive.org/web/20110728085232/http://www.medical.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/referenzwerte_pdf/IMMULITE_Systeme/prolaktin.pdf |date=28 July 2011 }} at medical.siemens.com—reference ranges as determined from the IMMULITE assay method</ref> The circumstances surrounding a given prolactin measurement (assay, patient condition, etc.) must therefore be considered before the measurement can be accurately interpreted.<ref name="Mancini2008" />

The following chart illustrates the variations seen in normal prolactin measurements across different populations. Prolactin values were obtained from specific control groups of varying sizes using the IMMULITE [[assay]].<ref name=immulite />

{{Bar graph
| title       = Typical prolactin values
| label_type  = Proband
| data_type   = Prolactin, μg/L (ng/mL)
| bar_width   = 35
| width_units = em
| data_max    = 113
| label1   = women, follicular phase (n = 803)
| data1    = 12.1
| label2   = women, luteal phase (n = 699)
| data2    = 13.9
| label3   = women, mid-cycle (n = 53)
| data3    = 17
| label4   = women, whole cycle (n = 1555)
| data4    = 13.0
| label5   = women, pregnant, 1st trimester (n = 39)
| data5    = 16
| label6   = women, pregnant, 2nd trimester (n = 52)
| data6    = 49
| label7   = women, pregnant, 3rd trimester (n = 54)
| data7    = 113
| label8   = Men, 21–30 (n = 50)
| data8    = 9.2
| label9   = Men, 31–40 (n = 50)
| data9    = 7.1
| label10   = Men, 41–50 (n = 50)
| data10    = 7.0
| label11   = Men, 51–60 (n = 50)
| data11    = 6.2
| label12   = Men, 61–70 (n = 50)
| data12    = 6.9
}}

=== Inter-method variability ===

The following table illustrates variability in reference ranges of serum prolactin between some commonly used assay methods (as of 2008), using a control group of healthy health care professionals (53 males, age 20–64 years, median 28 years; 97 females, age 19–59 years, median 29 years) in [[Essex]], England:<ref name="Beltran_2008">[http://www.clinchem.org/cgi/content/full/54/10/1673/T2 Table 2] {{Webarchive|url=https://web.archive.org/web/20111109064854/http://www.clinchem.org/cgi/content/full/54/10/1673/T2 |date=9 November 2011 }} in {{cite journal | vauthors = Beltran L, Fahie-Wilson MN, McKenna TJ, Kavanagh L, Smith TP | title = Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: evaluation and validation on common immunoassay platforms | journal = Clinical Chemistry | volume = 54 | issue = 10 | pages = 1673–81 | date = Oct 2008 | pmid = 18719199 | doi = 10.1373/clinchem.2008.105312 | doi-access = free }}</ref>
{|class="wikitable"
!rowspan = 2 valign = "bottom"| Assay method 
! colspan="2" |Mean<br />Prolactin
! colspan="2" |Lower limit <br /><span style="font-size:87%;">2.5th percentile</span>
! colspan="2" |Upper limit <br /><span style="font-size:87%;">97.5th percentile</span>
|-
| mIU/L 
| bgcolor="yellow" |             μg/L || mIU/L || bgcolor="yellow" | μg/L || mIU/L|| bgcolor="yellow" | μg/L  
|-
! colspan="9" | Females
|-
| Centaur  || 168   || bgcolor="yellow" | 7.92 || 71    || bgcolor="yellow" | 3.35 || 348|| bgcolor="yellow" | 16.4  
|-
| Immulite || 196   || bgcolor="yellow" | 9.25 || 75    || bgcolor="yellow" | 3.54 || 396|| bgcolor="yellow" | 18.7  
|-
| Access   || 192   || bgcolor="yellow" | 9.06 || 77    || bgcolor="yellow" | 3.63 || 408|| bgcolor="yellow" | 19.3  
|-
| Elecsys  || 222   || bgcolor="yellow" | 10.5  || 88    || bgcolor="yellow" | 4.15 || 492|| bgcolor="yellow" | 23.2 
|-
| Architect|| 225   || bgcolor="yellow" | 10.6  || 98    || bgcolor="yellow" | 4.62 || 447|| bgcolor="yellow" | 21.1 
|-
| AIA{{efn|name=aia|Beltran 2008 [http://www.clinchem.org/cgi/content/full/54/10/1673/T2 Table 2] {{Webarchive|url=https://web.archive.org/web/20111109064854/http://www.clinchem.org/cgi/content/full/54/10/1673/T2 |date=9 November 2011 }} reports measurements in mIU/L. AIA machines are calibrated to read the correct amount of μg/L against the second international standard IS 83/562, which has a potency of 27.0 mIU per μg.<ref>{{cite web |title=CL AIA-PACK® Prolactin TEST CUP |url=https://www.diagnostics.eu.tosohbioscience.com/File%20Library/TSEN/Secured%20files//IFU/CL_PRLTC_EN.pdf}}</ref> By converting these measurements to mIU/L, Beltran makes measurements from machines calibrated against the second and third IS comparable, because the third IS is calibrated against the second to maintain the magnitude of the IU. However, the raw readout of the machine will still be in μg/L of IS-83/562-equivalent, unlike the other machines which report in μg/L of IS-84/500-equivalent.}}|| 257|| bgcolor="yellow" |  {{#expr:257/27 round 2}} || 105 || bgcolor="yellow" |  {{#expr:105/27 round 2}}|| 548|| bgcolor="yellow" | {{#expr:548/27 round 2}}
|-
! colspan="9" | Males
|-
| Access   || 146   || bgcolor="yellow" | 6.89  || 58    || bgcolor="yellow" | 2.74 || 277|| bgcolor="yellow" | 13.1 
|-
| Centaur  || 167   || bgcolor="yellow" | 7.88  || 63    || bgcolor="yellow" | 2.97 || 262|| bgcolor="yellow" | 12.4 
|-
| Immulite || 158   || bgcolor="yellow" | 7.45  || 70    || bgcolor="yellow" | 3.30 || 281|| bgcolor="yellow" | 13.3 
|-
| Elecsys  || 180   || bgcolor="yellow" | 8.49  || 72    || bgcolor="yellow" | 3.40 || 331|| bgcolor="yellow" | 15.6 
|-
| Architect|| 188   || bgcolor="yellow" | 8.87  || 85    || bgcolor="yellow" | 4.01 || 310|| bgcolor="yellow" | 14.6 
|-
| AIA{{efn|name=aia}} || 211 || bgcolor="yellow" |  {{#expr:211/27 round 2}}|| 89|| bgcolor="yellow" |  {{#expr:89/27 round 2}}|| 365|| bgcolor="yellow" | {{#expr:365/27 round 2}}
|}

An example of the use of the above table is, if using the Centaur assay to estimate prolactin values in μg/L for females, the mean is 168&nbsp;mIU/L (7.92&nbsp;μg/L) and the reference range is 71–348&nbsp;mIU/L (3.35–16.4&nbsp;μg/L).

== Conditions ==

=== Elevated levels ===
[[Hyperprolactinaemia]], or excess serum prolactin, is associated with [[hypoestrogenism]], [[anovulatory]] [[infertility]], [[oligomenorrhoea]], [[amenorrhoea]], unexpected [[lactation]] and loss of [[libido]] in women and [[erectile dysfunction]] and loss of libido in men.<ref>Melmed S, Kleinberg D 2008 Anterior pituitary. 1n: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Willams textbook of endocrinology. 11th ed. Philadelphia: Saunders Elsevier; 185–261</ref>

'''Causes of Elevated Prolactin Levels'''

{{Col-begin}}
{{Col-break}}
'''Physiological'''
* [[Coitus]]
* Exercise
* Lactation
* Pregnancy
* Sleep
* Stress
* Depression
{{Col-break}}
'''Pharmacological'''
* [[Anesthetic]]s
* [[Anticonvulsant]]
* [[Antihistamine]]s (H2)
* [[Antihypertensives]]
* [[Cholinergic agonist]]
* Drug-induced hypersecretion
* Catecholamine depletor
* [[Dopamine receptor]] blockers
* Dopamine synthesis inhibitor
* [[Estrogen]]s
** [[Oral contraceptive]]s
** [[Oral contraceptive]] withdrawal
* [[Antipsychotic]]s
* [[Neuropeptide]]s
* [[Opioid]]s and opioid receptor antagonists
{{Col-break}}
'''Pathological'''
* Hypothalamic-pituitary stalk damage
** [[Granuloma]]s
** Infiltrations
** [[Radiation]]
** [[Rathke's cyst]]
* Trauma
** Pituitary stalk resection
** [[Suprasellar]] surgery
* Tumors
** [[Craniopharyngioma]]
** [[Germinoma]]
** Hypothalamic metastases
** [[Meningioma]]
** Suprasellar pituitary mass extension
* Surgery
{{Col-break}}
:&nbsp;
* Pituitary
** [[Acromegaly]]
** Idiopathic
** [[Lymphocytic hypophysitis]] or parasellar mass
** [[Macroadenoma]] (compressive)
** [[Macroprolactinemia]]
** [[Plurihumoral adenoma]]
** [[Prolactinoma]]
* Systemic disorders
** Chest-neurologic chest wall trauma
** [[Herpes Zoster]]
** Chronic [[renal failure]]
** [[Cirrhosis]]
** Cranial radiation
** [[Epileptic seizure]]s
** [[Polycystic ovarian disease]]
** [[Pseudocyesis]]
** Chronic low levels of [[thyroid hormone]]
{{col-end}}

=== Decreased levels ===
{{Main|Hypoprolactinemia}}
[[Hypoprolactinemia]], or serum prolactin deficiency, is associated with ovarian dysfunction in women,<ref name="Kauppila 1988" /><ref name="Schwarzler 1997" /> and [[Arteriogenesis|arteriogenic]] [[erectile dysfunction]], [[premature ejaculation]],<ref name="Corona 2009" /> [[oligozoospermia]], [[asthenospermia]], hypofunction of [[seminal vesicles]] and [[hypoandrogenism]]<ref name="Gonzales 1989" /> in men. In one study, normal sperm characteristics were restored when prolactin levels were raised to normal values in hypoprolactinemic men.<ref name="Ufearo 1995" />

Hypoprolactinemia can result from [[hypopituitarism]], excessive [[dopaminergic]] action in the [[tuberoinfundibular pathway]] and ingestion of [[D2 receptor|D<sub>2</sub> receptor]] [[agonist]]s such as [[bromocriptine]].{{cn|date=September 2023}}

==In medicine==
Prolactin is available commercially for use in other animals, but not in humans.<ref name="CouttsSmail2014">{{cite book| vauthors =  Coutts RT, Smail GA | title = Polysaccharides Peptides and Proteins: Pharmaceutical Monographs|url=https://books.google.com/books?id=ojGRBQAAQBAJ&pg=PA153|date=12 May 2014|publisher=Elsevier|isbn=978-1-4831-9612-1|pages=153–}}</ref> It is used to stimulate lactation in animals.<ref name="CouttsSmail2014" /> The [[biological half-life]] of prolactin in humans is around 15–20 minutes.<ref name="Horrobin2012">{{cite book|author=D.F. Horrobin|title=Prolactin: Physiology and Clinical Significance|url=https://books.google.com/books?id=h_Q-BAAAQBAJ&pg=PA13|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-010-9695-9|pages=13–}}</ref> The D<sub>2</sub> receptor is involved in the regulation of prolactin secretion, and agonists of the receptor such as [[bromocriptine]] and [[cabergoline]] decrease prolactin levels while antagonists of the receptor such as [[domperidone]], [[metoclopramide]], [[haloperidol]], [[risperidone]], and [[sulpiride]] increase prolactin levels.<ref name="Johnson2012">{{cite book|author=Martin H. Johnson|title=Essential Reproduction|url=https://books.google.com/books?id=qXpBst5hJs0C&pg=PT40|date=14 December 2012|publisher=John Wiley & Sons|isbn=978-1-118-42388-2|pages=40–}}</ref> D<sub>2</sub> receptor antagonists like domperidone, metoclopramide, and sulpiride are used as [[galactogogue]]s to increase prolactin secretion in the pituitary gland and induce lactation in humans.<ref name="Riordan2005">{{cite book|author=Jan Riordan|title=Breastfeeding and Human Lactation|url=https://books.google.com/books?id=aiVesab_2bwC&pg=PA468|date=January 2005|publisher=Jones & Bartlett Learning|isbn=978-0-7637-4585-1|pages=468–}}</ref>

==See also==
* [[Breast-feeding]]
* [[Breastfeeding and fertility]]
* [[Epileptic seizure]]
* [[Hyperprolactinaemia]]
* [[Hypothalamic–pituitary–prolactin axis]]
* [[Male lactation]]
* [[Prolactin modulator]]
* [[Prolactin receptor]]
* [[Prolactin-releasing hormone]]
* [[Prolactinoma]]
* [[Weaning]]

==References==
{{notelist}}
{{Reflist}}

==External links==
* {{MedlinePlusEncyclopedia|003718|Prolactin}}
* {{PDBe-KB2|P01236|Prolactin}}

{{Hormones}}
{{Amyloidosis}}
{{Galactagogues}}
{{Prolactin receptor modulators}}
{{Authority control}}

[[Category:Anterior pituitary hormones]]
[[Category:Breastfeeding]]
[[Category:Galactagogues]]
[[Category:Hormones of the hypothalamic-pituitary-prolactin axis]]
[[Category:Hormones of the pregnant female]]
[[Category:Human hormones]]
[[Category:Human female endocrine system]]
[[Category:Peptide hormones]]