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Prolactin - Wikipedia 4/19/2018 Prolactin - Wikipedia Prolactin Prolactin (PRL), also known as luteotropic hormone or luteotropin, is a protein that is best known for its role in PRL enabling mammals, usually females, to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans.[5] Prolactin is secreted from the pituitary gland in response to eating, mating, estrogen treatment, ovulation and nursing. Prolactin is secreted in pulses in between these events. Prolactin plays an essential role in metabolism, regulation of the immune system and pancreatic development. Discovered in non-human animals around 1930 by Oscar Riddle[6] and confirmed in humans in 1970 by Henry Friesen[7] Available structures [8] prolactin is a peptide hormone, encoded by the PRL gene. PDB Ortholog search: PDBe (https://www.ebi.ac.uk/ In mammals, prolactin is associated with milk production; in pdbe/searchResults.html?display=both&term= fish it is thought to be related to control of water and salt P06879%20or%20P01236) RCSB (http://www.r balance. Prolactin also acts in a cytokine-like manner and as an csb.org/pdb/search/smartSubquery.do?smartS important regulator of the immune system. It has important cell cycle-related functions as a growth-, differentiating- and earchSubtype=UpAccessionIdQuery&accessio anti-apoptotic factor. As a growth factor, binding to cytokine- nIdList=P06879,P01236) like receptors, it influences hematopoiesis, angiogenesis and is List of PDB id codes involved in the regulation of blood clotting through several pathways. The hormone acts in endocrine, autocrine and 1RW5 (http://www.rcsb.org/pdb/explore/explore.do?pdbId=1R paracrine manner through the prolactin receptor and a large W5), 2Q98 (http://www.rcsb.org/pdb/explore/explore.do?pdbI number of cytokine receptors.[5] d=2Q98), 3D48 (http://www.rcsb.org/pdb/explore/explore.do? pdbId=3D48), 3EW3 (http://www.rcsb.org/pdb/explore/explor Pituitary prolactin secretion is regulated by endocrine neurons e.do?pdbId=3EW3), 3MZG (http://www.rcsb.org/pdb/explore/ in the hypothalamus. The most important of these are the explore.do?pdbId=3MZG), 3N06 (http://www.rcsb.org/pdb/ex neurosecretory tuberoinfundibulum (TIDA) neurons of the plore/explore.do?pdbId=3N06), 3N0P (http://www.rcsb.org/pd arcuate nucleus that secrete dopamine (aka Prolactin b/explore/explore.do?pdbId=3N0P), 3NCB (http://www.rcsb.o Inhibitory Hormone) to act on the D receptors of lactotrophs, 2 rg/pdb/explore/explore.do?pdbId=3NCB), 3NCC (http://www.r causing inhibition of prolactin secretion. Thyrotropin-releasing csb.org/pdb/explore/explore.do?pdbId=3NCC), 3NCE (http:// factor (thyrotropin-releasing hormone) has a stimulatory effect www.rcsb.org/pdb/explore/explore.do?pdbId=3NCE), 3NCF on prolactin release, however prolactin is the only (http://www.rcsb.org/pdb/explore/explore.do?pdbId=3NCF), adenohypophyseal hormone whose principal control is 3NPZ (http://www.rcsb.org/pdb/explore/explore.do?pdbId=3N inhibitory. PZ) Several variants and forms are known per species. Many fish have variants prolactin A and prolactin B. Most vertebrates Identifiers including humans also have the closely related somatolactin. In Aliases PRL (https://www.genenames.org/cgi-bin/g humans, three smaller (4, 16 and 22 kDa) and several larger (so called big and big-big) variants exist. ene_symbol_report?hgnc_id=9445), GHA1, prolactin External MGI: 97762 (http://www.informatics.jax.org/ Contents IDs marker/MGI:97762) HomoloGene: 732 (http s://www.ncbi.nlm.nih.gov/entrez/query.fcgi? Functions cmd=Retrieve&db=homologene&dopt=Hom Regulation https://en.wikipedia.org/wiki/Prolactin 1/12 4/19/2018 Prolactin - Wikipedia Structure and isoforms oloGene&list_uids=732) GeneCards: PRL Prolactin receptor (https://www.genecards.org/cgi-bin/carddis Diagnostic use p.pl?gene=PRL) Units and unit conversions Reference ranges Gene location (Human) Inter-method variability Conditions Elevated levels Decreased levels In medicine See also References Chr. Chromosome 6 (human)[1] External links Functions Band 6p22.3 Start 22,287,244 bp[1] Prolactin has a wide variety of effects. It stimulates the End 22,297,501 bp[1] mammary glands to produce milk (lactation): increased serum concentrations of prolactin during pregnancy cause Gene location (Mouse) 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.[9] The hormone counteracts the effect of dopamine. Chr. Chromosome 13 (mouse)[2] Elevated levels of prolactin decrease the levels of sex hormones — estrogen in women and testosterone in men.[10] The effects of mildly elevated levels of prolactin are much more variable, in women, substantially increasing or decreasing estrogen levels. Band 13 A3.1|13 12.25 Start 27,057,570 bp[2] Prolactin is sometimes classified as a gonadotropin[11] although cM [2] in humans it has only a weak luteotropic effect while the effect End 27,065,205 bp of suppressing classical gonadotropic hormones is more Gene ontology important.[12] Prolactin within the normal reference ranges can act as a weak gonadotropin, but at the same time suppresses Molecular • prolactin receptor binding (http://amigo. GnRH secretion. The exact mechanism by which it inhibits function geneontology.org/amigo/term/GO:00051 GnRH is poorly understood. Although expression of prolactin 48) receptors (PRL-R) have been demonstrated in rat hypothalamus, the same has not been observed in GnRH • protein binding (http://amigo.geneontol neurons.[13] Physiologic levels of prolactin in males enhance ogy.org/amigo/term/GO:0005515) luteinizing hormone-receptors in Leydig cells, resulting in • hormone activity (http://amigo.geneont testosterone secretion, which leads to spermatogenesis.[14] ology.org/amigo/term/GO:0005179) Prolactin also stimulates proliferation of oligodendrocyte Cellular • extracellular region (http://amigo.geneo precursor cells. These cells differentiate into oligodendrocytes, component ntology.org/amigo/term/GO:0005576) the cells responsible for the formation of myelin coatings on axons in the central nervous system.[15] • endosome lumen (http://amigo.geneont ology.org/amigo/term/GO:0031904) Other actions include contributing to pulmonary surfactant synthesis of the fetal lungs at the end of the pregnancy and Biological • female pregnancy (http://amigo.geneon immune tolerance of the fetus by the maternal organism during process tology.org/amigo/term/GO:0007565) [16] pregnancy. Prolactin delays hair regrowth in mice. Prolactin • cellular protein metabolic process (htt promotes neurogenesis in maternal and fetal brains.[17][18] https://en.wikipedia.org/wiki/Prolactin 2/12 4/19/2018 Prolactin - Wikipedia Regulation p://amigo.geneontology.org/amigo/term/ GO:0044267) In humans, prolactin is produced at least in the anterior pituitary, decidua, myometrium, breast, lymphocytes, • cell surface receptor signaling pathway leukocytes and prostate.[19][20] A key regulator of prolactin (http://amigo.geneontology.org/amigo/ter production is estrogens that enhance growth of prolactin- m/GO:0007166) producing cells and stimulate prolactin production directly, as • JAK-STAT cascade involved in growth well as suppressing dopamine. hormone signaling pathway (http://amig In decidual cells and in lymphocytes the distal promoter and o.geneontology.org/amigo/term/GO:0060 thus prolactin expression is stimulated by cAMP. Responsivness to cAMP is mediated by an imperfect cAMP– 397) responsive element and two CAAT/enhancer binding proteins • lactation (http://amigo.geneontology.or (C/EBP).[20] Progesterone upregulates prolactin synthesis in g/amigo/term/GO:0007595) the endometrium and decreases it in myometrium and breast • cell proliferation (http://amigo.geneonto glandular tissue.[21] Breast and other tissues may express the Pit-1 promoter in addition to the distal promoter. logy.org/amigo/term/GO:0008283) • positive regulation of JAK-STAT Extrapituitary production of prolactin is thought to be special cascade (http://amigo.geneontology.org/ to humans and primates and may serve mostly tissue specific paracrine and autocrine purposes. It has been hypothesized amigo/term/GO:0046427) that in vertebrates such as mice a similar tissue specific effect is • regulation of multicellular organism achieved by a large family of prolactin-like proteins controlled growth (http://amigo.geneontology.org/a by at least 26 paralogous PRL genes not present in primates.[20] migo/term/GO:0040014) Vasoactive intestinal peptide and peptide histidine isoleucine • regulation of receptor activity (http://am help to regulate prolactin secretion in humans, but the igo.geneontology.org/amigo/term/GO:00 functions of these hormones in birds can be quite different.[22] 10469) Prolactin follows diurnal and ovulatory cycles. Prolactin levels • negative regulation of endothelial cell peak during REM sleep and in the early morning. Many proliferation (http://amigo.geneontology.o mammals experience a seasonal cycle. rg/amigo/term/GO:0001937) During pregnancy, high circulating concentrations of estrogen • negative regulation of angiogenesis (ht and progesterone increase prolactin levels by 10- to 20-fold. Estrogen and progesterone inhibit the stimulatory effects of tp://amigo.geneontology.org/amigo/term/ prolactin on milk production. The abrupt drop of estrogen and GO:0016525) progesterone levels following delivery allow prolactin—which • positive regulation of pri-miRNA temporarily
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