4/19/2018 - 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 in response to eating, mating, 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 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 (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 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 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 [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) -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 , 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 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 remains high—to induce lactation. transcription from RNA polymerase II Sucking on the nipple offsets the fall in prolactin as the internal promoter (http://amigo.geneontology.org/ stimulus for them is removed. The sucking activates amigo/term/GO:1902895) mechanoreceptors in and around the nipple. These signals are carried by nerve fibers through the spinal cord to the Sources:Amigo (http://amigo.geneontology.org/) / hypothalamus, where changes in the electrical activity of QuickGO (https://www.ebi.ac.uk/QuickGO/) neurons that regulate the pituitary gland increase prolactin Orthologs secretion. The suckling stimulus also triggers the release of oxytocin from the posterior pituitary gland, which triggers milk Species Human Mouse let-down: Prolactin controls milk production (lactogenesis) but Entrez not the milk-ejection reflex; the rise in prolactin fills the breast 5617 (https://www.ncbi.nl 19109 (https://www.ncbi.nl with milk in preparation for the next feed. m.nih.gov/entrez/query.fcg m.nih.gov/entrez/query.fcg i?db=gene&cmd=retrieve& i?db=gene&cmd=retrieve& In usual circumstances, in the absence of , dopt=default&list_uids=56 dopt=default&list_uids=19 lactation ceases within one or two weeks following the end of 17&rn=1) 109&rn=1) . https://en.wikipedia.org/wiki/Prolactin 3/12 4/19/2018 Prolactin - Wikipedia Levels can rise after exercise, high-protein meals, minor Ensembl ENSG00000172179 (htt ENSMUSG00000021342 surgical procedures,[23] following epileptic seizures[24] or due to p://www.ensembl.org/Hom (http://www.ensembl.org/M physical or emotional stress.[25][26] In a study on female o_sapiens/geneview?gene us_musculus/geneview?g volunteers under hypnosis, prolactin surges resulted from the =ENSG00000172179;db= ene=ENSMUSG00000021 evocation, with rage, of humiliating experiences, but not from core) 342;db=core) the fantasy of nursing.[26] UniProt Prolactin levels have also been found to rise with use of the P01236 (https://www.unipr P06879 (https://www.unipr drug MDMA.[27] ot.org/uniprot/P01236) ot.org/uniprot/P06879)

Hypersecretion is more common than hyposecretion. RefSeq Hyperprolactinemia is the most frequent abnormality of the NM_000948 (https://www. NM_001163530 (https://w anterior pituitary tumors, termed prolactinomas. (mRNA) ncbi.nlm.nih.gov/entrez/vie ww.ncbi.nlm.nih.gov/entre Prolactinomas may disrupt the hypothalamic-pituitary-gonadal wer.fcgi?val=NM_000948) z/viewer.fcgi?val=NM_001 axis as prolactin tends to suppress the secretion of GnRH from NM_001163558 (https://w 163530) the hypothalamus and in turn decreases the secretion of ww.ncbi.nlm.nih.gov/entre NM_011164 (https://www.n follicle-stimulating hormone (FSH) and luteinizing hormone z/viewer.fcgi?val=NM_001 cbi.nlm.nih.gov/entrez/vie (LH) from the anterior pituitary, therefore disrupting the 163558) wer.fcgi?val=NM_011164) ovulatory cycle.[28] Such hormonal changes may manifest as and in females as well as impotence in RefSeq NP_000939 (https://www.n NP_001157002 (https://ww males. Inappropriate lactation (galactorrhoea) is another (protein) cbi.nlm.nih.gov/entrez/vie w.ncbi.nlm.nih.gov/entrez/ important clinical sign of prolactinomas. wer.fcgi?val=NP_000939) viewer.fcgi?val=NP_00115 NP_001157030 (https://ww 7002) Structure and isoforms w.ncbi.nlm.nih.gov/entrez/ NP_035294 (https://www.n viewer.fcgi?val=NP_00115 cbi.nlm.nih.gov/entrez/vie The structure of prolactin is similar to that of 7030) wer.fcgi?val=NP_035294) 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 Location Chr 6: 22.29 – 22.3 Chr 13: 27.06 – immunoassays can give different results due to differing (UCSC) Mb (https://genome. 27.07 Mb (https://ge glycosylation, phosphorylation and sulfation, as well as ucsc.edu/cgi-bin/hgT nome.ucsc.edu/cgi-b degradation. The non-glycosylated form of prolactin is the racks?org=Human&d in/hgTracks?org=Mo dominant form at is secreted by the pituitary gland. MM,,KK,LLLL The three different sizes of prolactin are: b=hg38&position=ch use&db=mm0&positi r6:22287244-222975 on=chr13:27057570- Little prolactin—the predominant form.[29] It has a molecular weight of appxoximately 22-kDa.[29] It is a 01) 27065205) single-chain polypeptide of 198 amino acids and is [3] [4] apparently the result of removal of some amino acids. PubMed Big prolactin—approximately 48 kDa.[29] It may be the search product of interaction of several prolactin molecules. It appears to have little, if any, biological activity.[30] Wikidata Big big prolactin—approximately 150 kDa.[29] It appears to have a low biological activity.[31] View/Edit Human View/Edit Mouse The levels of larger ones are somewhat higher during the early postpartum period.[32]

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.[33] 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.[33]

Human prolactin receptors are insensitive to mouse prolactin.[34]

https://en.wikipedia.org/wiki/Prolactin 4/12 4/19/2018 Prolactin - Wikipedia Diagnostic use

Prolactin levels may be checked as part of a workup, as elevated prolactin secretion can suppress the secretion of FSH and GnRH, leading to 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.[35]

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 in international units (typically mIU/L). The current IU is calibrated against the third International Standard for Prolactin, IS 84/500.[36][37] Reference ampoules of IS 84/500 contain 2.5 µg of lyophilized human prolactin[38] and have been assigned an activity of .053 International Units.[36][37] Measurements that are calibrated against the current international standard can be converted into mass units using this ratio of grams to IUs;[39] prolactin concentrations expressed in mIU/L can be converted to µg/L by dividing by 21.2. Previous standards use other ratios.[40][41][42][43]

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.[39][40] Previous standards relied on prolactin from animal sources.[43] Purified human prolactin was scarce, heterogeneous, unstable and difficult to characterize. A preparation labelled 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.[39][41] It was determined that this preparation behaved anomalously in certain immunoassays and was not suitable as an IS.[39]

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.[36][37][39][42] 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.[42] Once stocks of these ampoules were depleted, 84/500 was established as the Third IS for human Prolactin.[36][39]

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.[33] Similarly, guidelines for diagnosing prolactin deficiency () are defined as prolactin levels below 3 µg/L in women[44][45] and 5 µg/L in men.[46][47][48] 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.[33][49] Furthermore, prolactin levels also vary factors including age,[50] sex,[50] stage[50] and pregnancy.[50] The circumstances surrounding a given prolactin measurement (assay, patient condition, etc.) must therefore be considered before the measurement can be accurately interpreted.[33]

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.[50] Typical prolactin values Proband Prolactin, µg/L women, follicular 12.1 phase (n = 803) women, luteal phase 13.9 (n = 699) women, mid- 17 https://en.wikipedia.org/wiki/Prolactin 5/12 4/19/2018 Prolactin - Wikipedia cycle (n = 53) women, whole cycle 13.0 (n = 1555) women, pregnant, 1st 16 trimester (n = 39) women, pregnant, 49 2nd trimester (n = 52) women, pregnant, 113 3rd trimester (n = 54) Men, 21–30 9.2 (n = 50) Men, 31–40 7.1 (n = 50) Men, 41–50 7.0 (n = 50) Men, 51–60 6.2 (n = 50) Men, 61–70 6.9 (n = 50)

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:[49]

https://en.wikipedia.org/wiki/Prolactin 6/12 4/19/2018 Prolactin - Wikipedia

Mean Lower limit Upper limit Prolactin 2.5th percentile 97.5th percentile Assay method µg/L mIU/L µg/L mIU/L µg/L mIU/L Females Centaur 7.92 168 3.35 71 16.4 348 Immulite 9.25 196 3.54 75 18.7 396 Access 9.06 192 3.63 77 19.3 408

AIA 9.52[51] 257[51] 3.89[51] 105[51] 20.3[51] 548[51] Elecsys 10.5 222 4.15 88 23.2 492 Architect 10.6 225 4.62 98 21.1 447 Males Access 6.89 146 2.74 58 13.1 277 Centaur 7.88 167 2.97 63 12.4 262 Immulite 7.45 158 3.30 70 13.3 281

AIA 7.81[51] 211[51] 3.30[51] 89[51] 13.5[51] 365[51] Elecsys 8.49 180 3.40 72 15.6 331 Architect 8.87 188 4.01 85 14.6 310

An example usage of table above is, if using the Centaur assay to estimate prolactin values in µg/L for females, the mean is 7.92 µg/L and the reference range is 3.35–16.4 µg/L.

Conditions

Elevated levels , 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.[52]

Physiological Pharmacological Pathological

Coitus Anesthetics Hypothalamic-pituitary Exercise Anticonvulsant stalk damage Pituitary Lactation Antihistamines Granulomas Acromegaly Pregnancy (H2) Infiltrations Idiopathic Sleep Antihypertensives Radiation Lymphocytic Stress Cholinergic Rathke's cyst hypophysitis or agonist Depression Trauma parasellar mass Drug-induced Macroadenoma hypersecretion Pituitary stalk (compressive) resection Catecholamine Macroprolactinemia depletor Suprasellar surgery Plurihumoral Dopamine Tumors adenoma receptor blockers Craniopharyngioma Prolactinoma Dopamine Germinoma Systemic disorders synthesis inhibitor Estrogens Hypothalamic metastases https://en.wikipedia.org/wiki/Prolactin 7/12 4/19/2018 Prolactin - Wikipedia Oral Meningioma Chest-neurologic contraceptives Suprasellar chest wall trauma Oral pituitary mass Herpes Zoster contraceptive extension Chronic renal withdrawal Surgery failure Neuroleptics Cirrhosis Antipsychotics Cranial radiation Neuropeptides Epileptic seizures Opiates and Polycystic ovarian opiate disease antagonists Pseudocyesis Chronic low levels of thyroid hormone

Decreased levels Hypoprolactinemia, or serum prolactin deficiency, is associated with ovarian dysfunction in women,[44][45] and arteriogenic erectile dysfunction, premature ejaculation,[46] oligozoospermia, asthenospermia, hypofunction of seminal vesicles and hypoandrogenism[47] in men. In one study, normal sperm characteristics were restored when prolactin levels were raised to normal values in hypoprolactinemic men.[48]

Hypoprolactinemia can result from hypopituitarism, excessive dopaminergic action in the tuberoinfundibular pathway and ingestion of D2 receptor agonists such as .

While there is evidence that women who smoke tend to breast feed for shorter periods, there is a wide variation of breast-feeding rates in women who do smoke. This suggest that psychosocial factors rather than physiological mechanisms (e.g., nicotine suppressing prolactin levels) are responsible for the lower rates of breast feeding in women who do smoke.[53][54]

In medicine

Prolactin is available commercially for use in animals, but not in humans.[55] It is used to stimulate lactation in animals.[55] The biological [56] half-life of prolactin in humans is around 15–20 minutes. The D2 receptor is involved in the regulation of prolactin secretion, and agonists of the receptor such as bromocriptine and decrease prolactin levels while antagonists of the receptor such as , [57] , haloperidol, , and increase prolactin levels. D2 receptor antagonists like domperidone, metoclopramide, and sulpiride are used as galactogogues to increase prolatin secretion and induce lactation in humans.[58]

See also

Breast-feeding Epileptic seizure Hyperprolactinaemia Hypothalamic–pituitary–prolactin axis Male lactation Prolactin receptor Prolactin-releasing hormone Prolactinoma Weaning

References

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Ufearo CS, Orisakwe OE (Sep 1995). "Restoration of normal sperm characteristics in hypoprolactinemic infertile men treated with metoclopramide and exogenous human prolactin". Clinical Pharmacology and Therapeutics. 58 (3): 354–9. doi:10.1016/0009- 9236(95)90253-8 (https://doi.org/10.1016%2F0009-9236%2895%2990253-8). PMID 7554710 (https://www.ncbi.nlm.nih.gov/pubmed/7 554710). 49. Table 2 (http://www.clinchem.org/cgi/content/full/54/10/1673/T2) in Beltran L, Fahie-Wilson MN, McKenna TJ, Kavanagh L, Smith TP (Oct 2008). "Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: evaluation and validation on common immunoassay platforms". Clinical Chemistry. 54 (10): 1673–81. doi:10.1373/clinchem.2008.105312 (https://doi.org/10.1373%2Fclinchem.2008.105312). PMID 18719199 (https://www.ncbi.nlm.nih.go v/pubmed/18719199). 50. Prolaktin (http://www.medical.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/referenzwerte_pdf/IMMULITE_Systeme/prolakti n.pdf) Archived (https://web.archive.org/web/20110728085232/http://www.medical.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/f iles/referenzwerte_pdf/IMMULITE_Systeme/prolaktin.pdf) 28 July 2011 at the Wayback Machine. at medical.siemens.com—reference ranges as determined from the IMMULITE assay method 51. The AIA essay values are also from Table 2 (http://www.clinchem.org/cgi/content/full/54/10/1673/T2) in Beltran 2008, like the other values, but it uses a different conversion factor of 27.0 mIU/L per µg/L, taken from the second international standard, IS 83/562). 52. 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 53. Amir LH (2001). "Maternal smoking and reduced duration of breastfeeding: a review of possible mechanisms". Early Human Development. 64 (1): 45–67. doi:10.1016/S0378-3782(01)00170-0 (https://doi.org/10.1016%2FS0378-3782%2801%2900170-0). PMID 11408108 (https://www.ncbi.nlm.nih.gov/pubmed/11408108). 54. Amir LH, Donath SM (2002). "Does maternal smoking have a negative physiological effect on breastfeeding? The epidemiological evidence". Birth (Berkeley, Calif.). 29 (2): 112–23. doi:10.1046/j.1523-536X.2002.00152.x (https://doi.org/10.1046%2Fj.1523-536X.200 2.00152.x). PMID 12000412 (https://www.ncbi.nlm.nih.gov/pubmed/12000412). 55. Coutts RT, Smail GA (12 May 2014). Polysaccharides Peptides and Proteins: Pharmaceutical Monographs (https://books.google.com/b ooks?id=ojGRBQAAQBAJ&pg=PA153). Elsevier. pp. 153–. ISBN 978-1-4831-9612-1. 56. D.F. Horrobin (6 December 2012). Prolactin: Physiology and Clinical Significance (https://books.google.com/books?id=h_Q-BAAAQBA J&pg=PA13). Springer Science & Business Media. pp. 13–. ISBN 978-94-010-9695-9. 57. Martin H. Johnson (14 December 2012). Essential Reproduction (https://books.google.com/books?id=qXpBst5hJs0C&pg=PT40). John Wiley & Sons. pp. 40–. ISBN 978-1-118-42388-2. 58. Jan Riordan (January 2005). Breastfeeding and Human Lactation (https://books.google.com/books?id=aiVesab_2bwC&pg=PA468). Jones & Bartlett Learning. pp. 468–. ISBN 978-0-7637-4585-1.

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Pathophysiology of Endocrine System—Prolactin at colostate.edu (https://web.archive.org/web/20050809082645/http://arbl.cvmbs.colo state.edu/hbooks/pathphys/endocrine/hypopit/prolactin.html) MedlinePlus Encyclopedia Prolactin (https://medlineplus.gov/ency/article/003718.htm) Prolactin (http://labtestsonline.org/understanding/analytes/prolactin/tab/test) - Lab Tests Online med/1098 (http://www.emedicine.com/med/topic1098.htm#) at eMedicine—"Hyperprolactinemia" med/1914 (http://www.emedicine.com/med/topic1914.htm#) at eMedicine—"Prolactin Deficiency" [1] (https://web.archive.org/web/20120917054024/http://www.endo-society.org/guidelines/final/upload/Diagnosis-Treatment-of-Hyperpro lactinemia.pdf) - "Endocrine Society Guidelines"

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