Prolactin

Prolactin
PRL structure.png
Identifiers
Symbol PRL
Entrez 5617
HUGO 9445
OMIM 176760
RefSeq NM_000948
UniProt P01236
Other data
Locus Chr. 6 p22.2-p21.3

Prolactin (PRL) or Luteotropic hormone (LTH) is a peptide hormone discovered by Dr. Henry Friesen, primarily associated with lactation. In breastfeeding, the act of an infant sucking the nipple stimulates the production of prolactin, which fills the breast with milk via a process called lactogenesis, in preparation for the next feed. Oxytocin, another hormone, is also released, which triggers milk let-down.

Contents

Production and regulation

The system of increased production is a positive feedback cycle. (That is, the effect causes more of itself.) This is one of the few instances in the body where positive feedback is normal.

Pituitary prolactin secretion is regulated by neuroendocrine neurons in the hypothalamus, the most important ones being the neurosecretory tuberoinfundibulum (TIDA) neurons of the arcuate nucleus, which secrete dopamine to act on the dopamine-2 receptors of lactotrophs, causing inhibition of prolactin secretion. Thyrotropin-releasing factor (thyrotropin-releasing hormone) has a stimulatory effect on prolactin release.

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.[1]

Effects

Prolactin has many effects including regulating lactation, orgasms, and stimulating proliferation of oligodendrocyte precursor cells.

It stimulates the mammary glands to produce milk (lactation): Increased serum concentrations of prolactin during pregnancy cause enlargement of the mammary glands of the breasts and increases the production of milk. However, the high levels of progesterone during pregnancy act directly on the breasts to stop ejection of milk. It is only when the levels of this hormone fall after childbirth that milk ejection is possible. Sometimes, newborn babies (males as well as females) secrete a milky substance from their nipples. This substance is commonly known as witch's milk. This is caused by the fetus being affected by prolactin circulating in the mother just before birth, and usually stops soon after birth.

Prolactin provides the body with sexual gratification after sexual acts: The hormone counteracts the effect of dopamine, which is responsible for sexual arousal. This is thought to cause the sexual refractory period.[2] The amount of prolactin can be an indicator for the amount of sexual satisfaction and relaxation. Unusually high amounts are suspected to be responsible for impotence and loss of libido (see hyperprolactinemia symptoms). 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.[3]

Prolactin also has a number of other effects including contributing to surfactant synthesis of the fetal lungs at the end of the pregnancy and immune tolerance of the fetus by the maternal organism during pregnancy; it also decreases normal levels of sex hormones — estrogen in women and testosterone in men.[4]. It is this inhibition of sex steroids that is responsible for loss of the menstrual cycle in lactating women as well as lactation-associated osteoporosis. Prolactin also enhances luteinizing hormone-receptors in Leydig cells, resulting in testosterone secretion which leads to spermatogenesis. Prolactin delays hair regrowth in mice[5].

Variance in levels

There is a diurnal as well as an ovulatory cycle in prolactin secretion. In many mammals, there is also a seasonal change in prolactin release.

During pregnancy, high circulating concentrations of estrogen promote prolactin production. The resulting high levels of prolactin secretion cause further maturation of the mammary glands, preparing them for lactation.

After childbirth, prolactin levels fall as the internal stimulus for them is removed. Sucking by the baby on the nipple then promotes further prolactin release, maintaining the ability to lactate. 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 cause increased 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 will cease within one or two weeks of the end of demand breastfeeding.

It has also been found that compared to un-mated males, fathers and expectant fathers have increased prolactin concentrations. [6]

High prolactin levels also tend to suppress the ovulatory cycle by inhibiting the secretion of both follicle-stimulating hormone (FSH) and gonadotropic-releasing hormone (GnRH). High prolactin levels can also contribute to mental health issues.

Prolactin levels peak during REM sleep, and in the early morning. Levels can rise after exercise, meals, sexual intercourse, minor surgical procedures [7], or following epileptic seizures.[8]

Structure

Prolactin is a single-chain polypeptide of 198 amino acids with a molecular weight of about 24,000 daltons. Its structure 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, sulfation, as well as degradation. The non-glycosylated form of prolactin is the dominant form of prolactin that is secreted by the pituitary gland.

Little prolactin is apparently the result of removal of some amino acids, whereas big prolactin can be the product of interaction of several prolactin molecules.

Pit-1 is a transcription factor that binds to the prolactin gene at several sites to allow for the production of prolactin in the pituitary gland. 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.

Human prolactin receptors are insensitive to mouse prolactin[9].

Prolactin receptor

Prolactin receptors are present in the mamillary glands, ovaries, pituitary glands, heart, lung, thymus, spleen, liver, pancreas, kidney, adrenal gland, uterus, skeletal muscle, skin and areas of the central nervous system. [10] 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 which initiates the JAK-STAT pathway. The activation of the prolactin receptor also results in the activation of mitogen-activated protein kinases and Src kinase. [10]

Diagnostic use

Prolactin levels may be checked as part of a sex hormone workup, as elevated prolactin secretion can suppress the secretion of FSH and GnRH, leading to hypogonadism, and sometimes causing erectile dysfunction in men.

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.[11]

Reference Levels

ng/mL mIU/L Prolactin Standard
Women 2.8-29.2 59-619 (World Health Organization [WHO]: Third International Reference Preparation [3rd IRP] of prolactin, human, lyophilized, 0.053 IU / ampoule, for immunoassay [preparation code:84/500][12])
Men 2.1-17.7 45-375 (WHO: 3rd IRP 84/500)

(Data from The Immunoassay Handbook, Third Edition.[13])

When measured under normal conditions in the morning most values fall into the range 4-12 ng/mL for women and 2-4 ng/mL for men. Measurement at other times of the day or after stress exposure will yield different values.

Conditions associated with elevated prolactin secretion

Hyperprolactinaemia is the term given to having too-high levels of prolactin in the blood, which can result from:

Conditions associated with decreased prolactin

Use of breastfeeding as contraceptive

The World Health Organization states that demand breastfeeding is more than 98% effective as a contraceptive in the first six months postpartum. This effect is said to be responsible for the natural spacing of children seen in countries where contraception is not widely available, and is thought to be an evolutionary means of ensuring adequate care is provided to each newborn. The 98% effectiveness applies only if three criteria are met:

  1. The mother has had no menstrual periods at all (amenorrhea)
  2. The baby is exclusively breast-fed
  3. It is six months or less since birth.

If one or more of these conditions are broken, lactational amenorrhea is no longer a reliable form of birth control. This contraceptive method is highly effective as long as the three conditions stated above are fulfilled. Further, the WHO suggests that a woman who is still amenorrheic has a less-than-5% chance of getting pregnant in the first year of her baby's life, as long as she is still breastfeeding on demand.

See also

References

  1. ↑ Kulick R, Chaiseha Y, Kang S, Rozenboim I, El Halawani M (2005). "The relative importance of vasoactive intestinal peptide and peptide histidine isoleucine as physiological regulators of prolactin in the domestic turkey". Gen Comp Endocrinol 142 (3): 267–73. doi:10.1016/j.ygcen.2004.12.024. PMID 15935152. 
  2. ↑ New Scientist article on prolactin function relating to sex - University of Paisley and the ETH Zürich
  3. ↑ Gregg C, Shikar V, Larsen P, et al. (2007). "White matter plasticity and enhanced remyelination in the maternal CNS". J. Neurosci. 27 (8): 1812–23. doi:10.1523/JNEUROSCI.4441-06.2007. PMID 17314279. 
  4. ↑ Prolactinoma - Mayo Clinic
  5. ↑ Craven AJ, Nixon AJ, Ashby MG, et al. (November 2006). "Prolactin delays hair regrowth in mice". J. Endocrinol. 191 (2): 415–25. doi:10.1677/joe.1.06685. PMID 17088411. http://joe.endocrinology-journals.org/cgi/content/abstract/191/2/415. 
  6. ↑ Nelson, R.J. (2005). An introduction to behavioral endocrinology (3rd ed.)/ Sunderland, MA: Sinauer Associates.
  7. ↑ Melmed S, Jameson JL (2005). "333 Disorders of the Anterior Pituitary and Hypothalamus". In Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL.. Harrison's principles of internal medicine (16th ed.). New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-140235-7. http://highered.mcgraw-hill.com/sites/0071402357/information_center_view0/. 
  8. ↑ Mellors JDC (2005). "The approach to patients with "non-epileptic seizures"". Postgrad Med J. 81 (958): 498–504. doi:10.1136/pgmj.2004.029785. PMID 16085740. 
  9. ↑ Utama FE, LeBaron MJ, Neilson LM, et al. (2006). "Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice". J. Endocrinol. 188 (3): 589–601. doi:10.1677/joe.1.06560. PMID 16522738. http://joe.endocrinology-journals.org/cgi/content/abstract/188/3/589. 
  10. ↑ 10.0 10.1 Mancini, T.; Casanueva, FF; Giustina, A (2008). "Hyperprolactinemia and Prolactinomas". Endocrinology & Metabolism Clinics of North America 37 (1): 67. doi:10.1016/j.ecl.2007.10.013. PMID 18226731. 
  11. ↑ Banerjee S, Paul P, Talib V (2004). "Serum prolactin in seizure disorders". Indian Pediatr 41 (8): 827–31. PMID 15347871. 
  12. ↑ "WHO Expert Committee on Biological Standardization". Thirty-ninth Report, WHO Technical Report Series. World Health Organization. 1989. http://whqlibdoc.who.int/trs/WHO_TRS_786.pdf. Retrieved 2009-06-03. "86.1520, WHO/BS documents: 86.1520 Add 1, 88.1596" 
  13. ↑ Wild D, ed (2005). The Immunoassay Handbook (Third ed.). Kidlington, Oxford, UK: Elsevier Science. pp. 930. ISBN 0080445268. 

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