Prolactin

Source: Wikipedia, the free encyclopedia.

PRL
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000172179

ENSMUSG00000021342

UniProt

P01236

P06879

RefSeq (mRNA)

NM_000948
NM_001163558

NM_001163530
NM_011164

RefSeq (protein)

NP_000939
NP_001157030

NP_001157002
NP_035294

Location (UCSC)Chr 6: 22.29 – 22.3 MbChr 13: 27.24 – 27.25 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] 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.[6][7]

Discovered in non-human animals around 1930 by Oscar Riddle[8] and confirmed in humans in 1970 by Henry Friesen,[9] prolactin is a peptide hormone, encoded by the PRL gene.[10]

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

paracrine manners through the prolactin receptor and numerous cytokine receptors.[5]

Pituitary prolactin secretion is regulated by endocrine neurons in the

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.[11]

Function

In humans

Prolactin has a wide variety of effects. It stimulates the

maternal behavior.[12]

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.[13]

In general, dopamine inhibits prolactin[14] but this process has feedback mechanisms.[15]

Elevated levels of prolactin decrease the levels of sex hormones—estrogen in women and testosterone in men.[16] 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

Leydig cells, resulting in testosterone secretion, which leads to spermatogenesis.[20]

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.[21]

Other actions include contributing to

fetal brains.[22][23]

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.[24]

In other vertebrates

The primary function of prolactin in fish is osmoregulation,[25] 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.[26] In the South American discus, prolactin may also regulate the production of a skin secretion that provides food for larval fry.[27] An increase in brooding behaviour caused by prolactin has been reported in hens.[28]

Prolactin and

autocrine fashion.[29][30] Elevated levels of prolactin can inhibit hair growth,[31] and knock-out mutations in the prolactin gene cause increased hair length in cattle[32] and mice.[30] Conversely, mutations in the prolactin receptor can cause reduced hair growth, resulting in the "slick" phenotype in cattle.[32][33] Additionally, prolactin delays hair regrowth in mice.[34]

Analogous to its effects on hair growth and shedding in mammals, prolactin in birds controls the

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.[37][38]

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.[39] 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.[40]

Prolactin receptor activation is essential for normal

wild-type counterparts.[41] Prolactin and prolactin receptor signaling are also essential for maturation of the mammary glands during pregnancy in mice.[41]

Regulation

In humans, prolactin is produced at least in the anterior pituitary,

leukocytes and prostate.[42][43]

Pituitary

Pituitary prolactin is controlled by the

Pit-1 transcription factor, which binds to the gene at several sites including a proximal promoter.[43] This promoter is inhibited by dopamine and stimulated by estrogens, neuropeptides, and growth factors.[44]
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.[45]

In birds (turkeys), VIP is a powerful prolactin-releasing factor, while

peptide histidine isoleucine has almost no effect.[46]

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).[43] Progesterone upregulates prolactin synthesis in the endometrium but decreases it in myometrium and breast glandular tissue.[47]

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.[45]

Extrapituitary production of prolactin is thought to be special to humans and primates and may serve mostly tissue-specific

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.[43]

Stimuli

Prolactin follows diurnal and ovulatory cycles. Prolactin levels peak during REM sleep and in the early morning. Many mammals experience a seasonal cycle.[38]

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.[48]

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

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.[45]

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,

stress.[51][52] 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.[52] Stress-induced PRL changes are not linked to the posterior pituitary in rodents.[45]

Hypersecretion is more common than hyposecretion. Hyperprolactinemia is the most frequent abnormality of the anterior pituitary tumors, termed

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.[53] Such hormonal changes may manifest as amenorrhea and infertility in females as well as erectile dysfunction in males.[54][7] Inappropriate lactation (galactorrhoea
) is another important clinical sign of prolactinomas.

Structure and isoforms

The structure of prolactin is similar to that of

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.[11]

The three different sizes of prolactin are:

The levels of larger ones are somewhat higher during the early postpartum period.[58]

Prolactin receptor

Main article: Prolactin receptor

Prolactin receptors are present in the

Src kinase.[59]

Human prolactin receptors are insensitive to mouse prolactin.[60]

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.[61]

Prolactin levels may be of some use in distinguishing

psychogenic non-epileptic seizures. The serum prolactin level usually rises following an epileptic seizure.[62]

Units and unit conversions

The serum concentration of prolactin can be given in

lyophilized human prolactin[65] and have been assigned an activity of .053 International Units.[63][64] Measurements that are calibrated against the current international standard can be converted into mass units using this ratio of grams to IUs;[66] prolactin concentrations expressed in mIU/L can be converted to µg/L by dividing by 21.2. Previous standards use other ratios.[67][68][69][70]

The first

immunoassays and was not suitable as an IS.[66]

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.[63][64][66][69] 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.[69] Once stocks of these ampoules were depleted, 84/500 was established as the Third IS for human prolactin.[63][66]

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.[59] Similarly, guidelines for diagnosing prolactin deficiency (hypoprolactinemia) are defined as prolactin levels below 3 µg/L in women[71][72] and 5 µg/L in men.[73][74][75] 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.[59][76] Furthermore, prolactin levels vary according to factors as age,[77] sex,[77] menstrual cycle stage[77] and pregnancy.[77] The circumstances surrounding a given prolactin measurement (assay, patient condition, etc.) must therefore be considered before the measurement can be accurately interpreted.[59]

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.[77]

Typical prolactin values
Proband Prolactin, µg/L (ng/mL)
women, follicular phase (n = 803)
12.1
women, luteal phase (n = 699)
13.9
women, mid-cycle (n = 53)
17
women, whole cycle (n = 1555)
13.0
women, pregnant, 1st trimester (n = 39)
16
women, pregnant, 2nd trimester (n = 52)
49
women, pregnant, 3rd trimester (n = 54)
113
Men, 21–30 (n = 50)
9.2
Men, 31–40 (n = 50)
7.1
Men, 41–50 (n = 50)
7.0
Men, 51–60 (n = 50)
6.2
Men, 61–70 (n = 50)
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:[76]

Assay method Mean
Prolactin		 Lower limit
2.5th percentile		 Upper limit
97.5th percentile
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[78] 257[78] 3.89[78] 105[78] 20.3[78] 548[78]
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[78] 211[78] 3.30[78] 89[78] 13.5[78] 365[78]
Elecsys 8.49 180 3.40 72 15.6 331
Architect 8.87 188 4.01 85 14.6 310

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 7.92 µg/L and the reference range is 3.35–16.4 µg/L.

Conditions

Elevated levels

amenorrhoea, unexpected lactation and loss of libido in women and erectile dysfunction and loss of libido in men.[79]

Causes of Elevated Prolactin Levels

Decreased levels

Main article: Hypoprolactinemia

hypoandrogenism[74] in men. In one study, normal sperm characteristics were restored when prolactin levels were raised to normal values in hypoprolactinemic men.[75]

Hypoprolactinemia can result from

D2 receptor agonists such as bromocriptine.[citation needed
]

In medicine

Prolactin is available commercially for use in other animals, but not in humans.

galactogogues to increase prolactin secretion in the pituitary gland and induce lactation in humans.[83]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000172179 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021342 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^
    PMID 9626554
    .
  6. S2CID 37979194
    .
  7. ^
    PMID 34095489
    .
  8. ^ Bates R, Riddle O (November 1935). "The preparation of prolactin". Journal of Pharmacology and Experimental Therapeutics. 55 (3): 365–371.
  9. PMID 5483096.[permanent dead link
    ]
  10. ^ Evans AM, Petersen JW, Sekhon GS, DeMars R (May 1989). "Mapping of prolactin and tumor necrosis factor-beta genes on human chromosome 6p using lymphoblastoid cell deletion mutants". Somatic Cell and Molecular Genetics. 15 (3): 203–13.
    S2CID 36302971
    .
  11. ^
    ISBN 978-0-12-801238-3
    , retrieved 10 January 2024
  12. PMID 9751488
    .
  13. S2CID 19824793
    .
  14. PMID 2866952
    .
  15. PMID 11015620
    .
  16. ^ Prolactinoma—Mayo Clinic
  17. ISBN 978-0-8053-5909-1
    .
  18. ^ Gonadotropins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  19. PMID 17569755
    .
  20. PMID 12087074
    .
  21. PMID 17314279
    .
  22. S2CID 38577726
    .
  23. S2CID 27182670
    .
  24. S2CID 45981792
    .
  25. PMID 16406056
    .
  26. PMID 23791758
    .
  27. PMID 19272315
    .
  28. PMID 15971519
    .
  29. PMID 12707045
    .
  30. ^
    PMID 11356702
    .
  31. PMID 16507890
    .
  32. ^
    PMID 25519203
    .
  33. PMID 29527221
    .
  34. PMID 17088411
    .
  35. PMID 16530194
    .
  36. PMID 29566646
    .
  37. PMID 37289658
    .
  38. ^
    PMID 35686456
    .
  39. S2CID 208985116
    .
  40. S2CID 4953983
    .
  41. ^
    S2CID 24217896
    .
  42. PMID 8969972
    .
  43. ^
    PMID 16998840
    .
  44. ^ Ben-Jonathan N. (2001) Hypothalamic control of prolactin synthesis and secretion . In: Horseman ND, ed. Prolactin. Boston: Kluwer; 1 –24
  45. ^
    PMID 18057139. {{cite journal}}: Check |url= value (help
    )
  46. PMID 15935152
    .
  47. PMID 12574200
    .
  48. PMID 35163554
    .
  49. ISBN 978-0-07-140235-4
    .
  50. PMID 16085740
    .
  51. ^ "Prolactin". MedLine plus. Retrieved 24 October 2014.
  52. ^
    S2CID 1335211
    .
  53. ^ Welt CK, Barbieri RL, Geffner ME (2020). "Etiology, diagnosis, and treatment of secondary amenorrhea". UpToDate. Waltham, MA. Retrieved 7 November 2013.
  54. PMID 30072818
    .
  55. ^
    PMID 752015
    .
  56. PMID 263349
    .
  57. S2CID 42796831
    .
  58. PMID 8291454
    .
  59. ^
    PMID 18226731
    .
  60. PMID 16522738
    .
  61. PMID 29939606
    , retrieved 10 January 2024
  62. PMID 15347871
    .
  63. ^
    PMID 2715755
    .
  64. ^ a b c "WHO Expert Committee on Biological Standardization" (PDF). Thirty-ninth Report, WHO Technical Report Series. World Health Organization. 1989. Retrieved 3 June 2009. 86.1520, WHO/BS documents: 86.1520 Add 1, 88.1596
  65. ^ "WHO International Standard, Prolactin, Human. NIBSC code: 84/500, Instructions for use" (PDF). NIBSC / Health Protection Agency. 1989. Archived from the original (PDF) on 3 October 2011. Retrieved 21 March 2011.
  66. ^
    PMID 1477965
    .
  67. ^
    PMID 429949
    .
  68. ^ a b "WHO Expert Committee on Biological Standardization" (PDF). Thirty-fifth Report, WHO Technical Report Series. World Health Organization. 1985. Retrieved 21 March 2011.
  69. ^ a b c "WHO Expert Committee on Biological Standardization" (PDF). Thirty-seventh Report, WHO Technical Report Series. World Health Organization. 1987. Retrieved 21 March 2011.[dead link]
  70. ^
    PMID 14107744
    .
  71. ^
    PMID 3342895
    .
  72. ^
    PMID 9341613
    .
  73. ^
    PMID 19210705
    .
  74. ^
    PMID 2619414
    .
  75. ^
    S2CID 1735908
    .
  76. ^
    PMID 18719199
    .
  77. ^ a b c d e Prolaktin Archived 28 July 2011 at the Wayback Machine at medical.siemens.com—reference ranges as determined from the IMMULITE assay method
  78. ^ a b c d e f g h i j k l The AIA essay values are also from Table 2 Archived 9 November 2011 at the Wayback Machine 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).
  79. ^ 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
  80. ^
    ISBN 978-1-4831-9612-1
    .
  81. ISBN 978-94-010-9695-9
    .
  82. ISBN 978-1-118-42388-2
    .
  83. ISBN 978-0-7637-4585-1
    .

External links
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