prolactin prolactin prolactin (prl), also known as lactotropin, 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. 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. prlavailable structurespdbortholog search: pdbe rcsb list of pdb id codes1rw5, 2q98, 3d48, 3ew3, 3mzg, 3n06, 3n0p, 3ncb, 3ncc, 3nce, 3ncf, 3npzidentifiersaliasesprl, gha1, prolactinexternal idsomim: 176760 mgi: 97762 homologene: 732 genecards: prl gene location (human)chr.chromosome 6 (human)band6p22.3start22,287,244 bpend22,302,826 bpgene location (mouse)chr.chromosome 13 (mouse)band13 a3.1|13 12.25 cmstart27,241,553 bpend27,249,188 bprna expression patternbgeehumanmouse (ortholog)top expressed inpituitary glandanterior pituitarystromal cell of endometriumgastric mucosasecondary oocyteright coronary arterytibialis anterior musclemyometriumthymusembryotop expressed inpituitary glandanterior pituitarycingulate gyrussuperior frontal gyrussensory ganglioncochleaamygdalavisual cortexsubstantia nigracerebellummore reference expression databiogpsn/agene ontologymolecular function prolactin receptor binding protein binding hormone activity cellular component extracellular region endosome lumen secretory granule extracellular space biological process female pregnancy cell surface receptor signaling pathway growth hormone receptor signaling pathway via jak-stat lactation cell population proliferation positive regulation of receptor signaling pathway via jak-stat regulation of multicellular organism growth regulation of signaling receptor activity negative regulation of endothelial cell proliferation negative regulation of angiogenesis positive regulation of pri-mirna transcription by rna polymerase ii birth response to nutrient circadian rhythm positive regulation of cell population proliferation response to organic cyclic compound regulation of ossification response to estradiol response to lipopolysaccharide cellular response to hormone stimulus multicellular organismal response to stress ovulation cycle response to ethanol positive regulation of epithelial cell proliferation mammary gland development response to nutrient levels positive regulation of lactation sources:amigo / quickgoorthologsspecieshumanmouseentrez561719109ensemblensg00000172179ensmusg00000021342uniprotp01236p06879refseq (mrna)nm_000948nm_001163558nm_001163530nm_011164refseq (protein)np_000939np_001157030np_001157002np_035294location (ucsc)chr 6: 22.29 – 22.3 mbchr 13: 27.24 – 27.25 mbpubmed searchwikidataview/edit humanview/edit mouse discovered in non-human animals around 1930 by oscar riddle and confirmed in humans in 1970 by henry friesen, prolactin is a peptide hormone, encoded by the prl gene. 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. 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, three smaller (4, 16, and 23 kda) and several larger (so-called big and big-big) variants exist. 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. 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. in general, dopamine inhibits prolactin but this process has feedback mechanisms. elevated levels of prolactin decrease the levels of sex hormones—estrogen in women and testosterone in men. 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 although in humans it has only a weak luteotropic effect while the effect of suppressing classical gonadotropic hormones is more important. 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. physiologic levels of prolactin in males enhance luteinizing hormone-receptors in leydig cells, resulting in testosterone secretion, which leads to spermatogenesis. 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. 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. 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. in other vertebrates the primary function of prolactin in fish is osmoregulation, 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. in the south american discus, prolactin may also regulate the production of a skin secretion that provides food for larval fry. an increase in brooding behaviour caused by prolactin has been reported in hens. 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. elevated levels of prolactin can inhibit hair growth, and knock-out mutations in the prolactin gene cause increased hair length in cattle and mice. conversely, mutations in the prolactin receptor can cause reduced hair growth, resulting in the "slick" phenotype in cattle. additionally, prolactin delays hair regrowth in mice. analogous to its effects on hair growth and shedding in mammals, prolactin in birds controls the moulting of feathers, as well as the age at onset of feathering in both turkeys and chickens. 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. 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. regulation in humans, prolactin is produced at least in the anterior pituitary, decidua, myometrium, breast, lymphocytes, leukocytes and prostate. pituitary prolactin is controlled by the pit-1 transcription factor that binds to the prolactin gene at several sites. ultimately dopamine, extrapituitary prolactin is controlled by a superdistal promoter and apparently unaffected by dopamine. the thyrotropin-releasing hormone and the vasoactive intestinal peptide stimulate the secretion of prolactin in experimental settings, however their physiological influence is unclear. the main stimulus for prolactin secretion is suckling, the effect of which is neuronally mediated. a key regulator of prolactin production is estrogens that enhance growth of prolactin-producing cells and stimulate prolactin production directly, as well as suppressing dopamine. in decidual cells and in lymphocytes the distal promoter and thus prolactin expression is stimulated by camp. responsivness to camp is mediated by an imperfect camp–responsive element and two caat/enhancer binding proteins (c/ebp). progesterone upregulates prolactin synthesis in the endometrium and decreases it in myometrium and breast glandular tissue. breast and other tissues may express the pit-1 promoter in addition to the distal promoter. 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. vasoactive intestinal peptide and peptide histidine isoleucine help to regulate prolactin secretion in humans, but the functions of these hormones in birds can be quite different. prolactin follows diurnal and ovulatory cycles. prolactin levels peak during rem sleep and in the early morning. many mammals experience a seasonal cycle. 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. 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. 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, following epileptic seizures or due to physical or emotional stress. 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. 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. such hormonal changes may manifest as amenorrhea and infertility in females as well as erectile dysfunction in males. 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. the three different sizes of prolactin are: little prolactin—the predominant form. it has a molecular weight of approximately 23-kda. 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. it may be the product of interaction of several prolactin molecules. it appears to have little, if any, biological activity. big big prolactin—approximately 150 kda. it appears to have a low biological activity. the levels of larger ones are somewhat higher during the early postpartum period. prolactin receptor 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. 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. human prolactin receptors are insensitive to mouse prolactin. 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. 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. units and unit conversions the serum