Prolactin

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Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to 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>Template:Cite journal</ref><ref name="auto">Template:Cite journal</ref>

Discovered in non-human animals around 1930 by Oscar Riddle<ref name="Riddle_1935"> Template:Cite journal</ref> and confirmed in humans in 1970 by Henry Friesen,<ref name="Friesen_1970">Template:Cite journal</ref> prolactin is a peptide hormone, encoded by the PRL gene.<ref name="pmid2567059"> Template:Cite journal</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, and paracrine manners through the prolactin receptor and numerous cytokine receptors.<ref name="Bole-Feysot_1998">Template:Cite journal</ref>

Pituitary prolactin secretion is regulated by endocrine neurons in the hypothalamus. The most important of these are the neurosecretory tuberoinfundibulum (TIDA) neurons of the arcuate nucleus that secrete dopamine (a.k.a. Prolactin Inhibitory Hormone) to act on the D₂ receptors of lactotrophs, causing inhibition of prolactin secretion. Thyrotropin-releasing hormone has a 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">Template:Citation</ref>

Function

In humans

Prolactin has a wide variety of effects. It stimulates the mammary glands 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 behavior.<ref name="pmid9751488">Template:Cite journal</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">Template:Cite journal</ref>

In general, dopamine inhibits prolactin<ref name="pmid2866952">Template:Cite journal</ref> but this process has feedback mechanisms.<ref name=Freeman>Template:Cite journal</ref>

Elevated levels of prolactin decrease the levels of sex hormones—estrogen in women and testosterone in men.<ref>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">Template:Cite book</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">Template:MeSH name</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>Template:Cite journal</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">Template:Cite journal</ref>

Prolactin also stimulates proliferation of oligodendrocyte precursor cells. These cells differentiate into oligodendrocytes, the cells responsible for the formation of myelin coatings on axons in the central nervous system.<ref name="pmid17314279">Template:Cite journal</ref>

Other actions include contributing to pulmonary surfactant synthesis of the fetal lungs 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">Template:Cite journal</ref><ref name="pmid21820505">Template:Cite journal</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">Template:Cite journal</ref>

In other vertebrates

The primary function of prolactin in fish is osmoregulation,<ref name="pmid16406056">Template:Cite journal</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">Template:Cite journal</ref> In the South American discus, prolactin may also regulate the production of a skin secretion that provides food for larval fry.<ref name="pmid19272315">Template:Cite journal</ref> An increase in brooding behaviour caused by prolactin has been reported in hens.<ref name="pmid15971519">Template:Cite journal</ref>

Prolactin and 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">Template:Cite journal</ref><ref name="pmid11356702">Template:Cite journal</ref> Elevated levels of prolactin can inhibit hair growth,<ref name="pmid16507890">Template:Cite journal</ref> and knock-out mutations in the prolactin gene cause increased hair length in cattle<ref name="pmid25519203">Template:Cite journal</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">Template:Cite journal</ref> Additionally, prolactin delays hair regrowth in mice.<ref name="pmid17088411">Template:Cite journal</ref>

Analogous to its effects on hair growth and shedding in mammals, prolactin in birds controls the moulting of feathers,<ref name="pmid16530194">Template:Cite journal</ref> as well as the age at onset of feathering in both turkeys and chickens.<ref name="pmid29566646">Template:Cite journal</ref> Pigeons, flamingos and male emperor penguins feed their young a cheese-like secretion from the upper digestive tract called crop milk, whose production is regulated by prolactin.<ref>Template:Cite journal</ref><ref name=":1">Template:Cite journal</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>Template:Cite journal</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>Template:Cite journal</ref>

Prolactin receptor activation is essential for normal mammary gland development during puberty in mice.<ref name="pmid10935023">Template:Cite journal</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">Template:Cite journal</ref><ref name="Gerlo_2006">Template:Cite journal</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 VIP and TRH, but humans seem to only react to TRH. There are prolactin-releasing peptides 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>Template:Cite journal</ref>

In birds (turkeys), VIP is a powerful prolactin-releasing factor, while peptide histidine isoleucine has almost no effect.<ref>Template:Cite journal</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 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>Template:Cite journal</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

Prolactin follows diurnal and 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>Template:Cite journal</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>Template:Cite book</ref> following epileptic seizures<ref name="Mellors">Template:Cite journal</ref> or due to physical or emotional stress.<ref name="medlineplus">Template:Cite news</ref><ref name="sobrinho-2003">Template:Cite journal</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 prolactinomas. 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 ovulatory cycle.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Such hormonal changes may manifest as amenorrhea and infertility in females as well as erectile dysfunction in males.<ref>Template:Cite journal</ref><ref name="auto"/> Inappropriate lactation (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 bonds. Significant heterogeneity of the molecule has been described, thus bioassays and immunoassays 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">Template:Cite journal, in turn citing: Template:Cite journal</ref> It has a molecular weight of approximately 23-kDa.<ref name="Sabharwal_1992"/> It is a single-chain polypeptide of 199 amino acids 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>Template:Cite journal</ref>
• Macroprolactin—approximately 150 kDa.<ref name="Sabharwal_1992"/> It appears to have a low biological activity.<ref name="pmid1483294">Template:Cite journal</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">Template:Cite journal</ref>

Prolactin receptor

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Prolactin receptors are present in the mammillary glands, 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>Template:Cite journal</ref> When prolactin binds to the receptor, it causes it to 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">Template:Cite journal</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>Template:Citation</ref>

Prolactin levels may be of some use in distinguishing epileptic seizures from psychogenic non-epileptic seizures. The serum prolactin level usually rises following an epileptic seizure.<ref>Template:Cite journal</ref>

Units and unit conversions

The serum concentration of prolactin can be given in mass concentration (μg/L or ng/mL), molar concentration (nmol/L or pmol/L), or international units (typically mIU/L). The current IU is calibrated against the third International Standard for Prolactin, IS 84/500.<ref name="Schulster 1989">Template:Cite journal</ref><ref name="urlwhqlibdoc.who.int">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Reference ampoules of IS 84/500 contain "approximately" 2.5 μg of lyophilized human prolactin<ref name="NIBSC instructions">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</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">Template:Cite journal</ref><ref name="second IRP">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="second IS">{{#invoke:citation/CS1|citation |CitationClass=web }}Template:Dead linkTemplate:Cbignore</ref><ref name=who1963>Template:Cite journal</ref>

The first 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 polymers 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 mIU per ampoule when calibrated against the third IS and contains 1.002 g of human pituitary extract each (which is then lyophilized). Each ampoule contains approximately 3.2 μg of prolactin. The assigned value will be 67 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Reference ranges

General guidelines for diagnosing prolactin excess (hyperprolactinemia) define the upper threshold of normal prolactin at 25 μg/L for women and 20 μg/L for men.<ref name="Mancini2008" /> Similarly, guidelines for diagnosing prolactin deficiency (hypoprolactinemia) are defined as prolactin levels below 3 μg/L in women<ref name="Kauppila 1988">Template:Cite journal</ref><ref name="Schwarzler 1997">Template:Cite journal</ref> and 5 μg/L in men.<ref name="Corona 2009">Template:Cite journal</ref><ref name="Gonzales 1989">Template:Cite journal</ref><ref name="Ufearo 1995">Template:Cite journal</ref> However, different assays and methods for measuring prolactin are employed by different laboratories and as such the 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>Prolaktin Template:Webarchive 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 />

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">Table 2 Template:Webarchive in Template:Cite journal</ref>

Assay method	Mean Prolactin		Lower limit 2.5th percentile		Upper limit 97.5th percentile
	mIU/L	μg/L	mIU/L	μg/L	mIU/L	μg/L
Females
Centaur	168	7.92	71	3.35	348	16.4
Immulite	196	9.25	75	3.54	396	18.7
Access	192	9.06	77	3.63	408	19.3
Elecsys	222	10.5	88	4.15	492	23.2
Architect	225	10.6	98	4.62	447	21.1
AIATemplate:Efn	257	{{#expr:257/27 round 2}}	105	{{#expr:105/27 round 2}}	548	{{#expr:548/27 round 2}}
Males
Access	146	6.89	58	2.74	277	13.1
Centaur	167	7.88	63	2.97	262	12.4
Immulite	158	7.45	70	3.30	281	13.3
Elecsys	180	8.49	72	3.40	331	15.6
Architect	188	8.87	85	4.01	310	14.6
AIATemplate:Efn	211	{{#expr:211/27 round 2}}	89	{{#expr:89/27 round 2}}	365	{{#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 mIU/L (7.92 μg/L) and the reference range is 71–348 mIU/L (3.35–16.4 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

Template:Col-begin Template:Col-break Physiological

• Coitus
• Exercise
• Lactation
• Pregnancy
• Sleep
• Stress
• Depression

Template:Col-break Pharmacological

• Anesthetics
• Anticonvulsant
• Antihistamines (H2)
• Antihypertensives
• Cholinergic agonist
• Drug-induced hypersecretion
• Catecholamine depletor
• Dopamine receptor blockers
• Dopamine synthesis inhibitor
• Estrogens
  • Oral contraceptives
  • Oral contraceptive withdrawal
• Antipsychotics
• Neuropeptides
• Opioids and opioid receptor antagonists

Template:Col-break Pathological

• Hypothalamic-pituitary stalk damage
  • Granulomas
  • Infiltrations
  • Radiation
  • Rathke's cyst
• Trauma
  • Pituitary stalk resection
  • Suprasellar surgery
• Tumors
  • Craniopharyngioma
  • Germinoma
  • Hypothalamic metastases
  • Meningioma
  • Suprasellar pituitary mass extension
• Surgery

 

• 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 seizures
  • Polycystic ovarian disease
  • Pseudocyesis
  • Chronic low levels of thyroid hormone

Decreased levels

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Hypoprolactinemia, or serum prolactin deficiency, is associated with ovarian dysfunction in women,<ref name="Kauppila 1988" /><ref name="Schwarzler 1997" /> and 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 agonists such as bromocriptine.Template:Cn

In medicine

Prolactin is available commercially for use in other animals, but not in humans.<ref name="CouttsSmail2014">Template:Cite book</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">Template:Cite book</ref> The D₂ 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">Template:Cite book</ref> D₂ receptor antagonists like domperidone, metoclopramide, and sulpiride are used as galactogogues to increase prolactin secretion in the pituitary gland and induce lactation in humans.<ref name="Riordan2005">Template:Cite book</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

External links

• Template:MedlinePlusEncyclopedia
• Template:PDBe-KB2