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Prolactin (PRL) or Luteotropic hormone (LTH) is a peptide hormone primarily associated with lactation. In breastfeeding, the act of an infant suckling 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.
Production and regulationEdit
Prolactin or luteotropic hormone is synthesised and secreted by lactotrope cells in the adenohypophysis (anterior pituitary gland). It is also produced in other tissues including the breast, the decidua, parts of the central nervous system and the immune system.  The gene encoding prolactin in humans is located on chromosome 6.
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 (D2-R) of lactotrophs, causing inhibition of prolactin secretion. Thyrotropin-releasing factor has a stimulatory effect on prolactin release.
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. 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.
Variance in levelsEdit
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.
Increasing prolactin levels in women during pregnancy (especially within first 3 months) and then in the breastfeeding period are responsible for cycles of high sexual satiation, which help protect the child and are amidst natural rewards for procreation. However, fluctuations and drops of this hormone occurring in that period can substantially increase sexual tension and in turn often work for higher desire for orgasms.
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 is a single-chain polypeptide of 199 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.
- Main article: 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.  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. 
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.
Conditions associated with elevated prolactin secretionEdit
Hyperprolactinaemia is the term given to having too-high levels of prolactin in the blood.
- Excess thyrotropin-releasing hormone (TRH), usually in primary hypothyroidism
- Many anti-psychotic medications
- Emotional stress
- Pregnancy and Lactation.
Conditions associated with decreased prolactinEdit
Use of breastfeeding as contraceptiveEdit
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:
- The mother has had no menstrual periods at all (amenorrhea)
- The baby is exclusively breast-fed
- It is six months or less since birth.
- A fourth criteria has also been mentioned: The baby does not go for longer than 5 hours between feedings (i.e. while sleeping)
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.
- Male lactation
- Prolactin receptor
- Psychogenic non-epileptic seizures
- ↑ 1.0 1.1 1.2 Mancini, T. (2008), "Hyperprolactinemia and Prolactinomas", Endocrinology & Metabolism Clinics of North America 37: 67, doi:10.1016/j.ecl.2007.10.013, PMID 18226731
- ↑ 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.
- ↑ New Scientist article on prolactin function relating to sex - University of Paisley and the ETH Zürich
- ↑ 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.
- ↑ Melmed S, Jameson JL (2005). "333 Disorders of the Anterior Pituitary and Hypothalamus" 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.
- ↑ Mellors JDC (2005). The approach to patients with "non-epileptic seizures". Postgrad Med J. 81 (958): 498-504.
- ↑ 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.
- ↑ Banerjee S, Paul P, Talib V (2004). Serum prolactin in seizure disorders. Indian Pediatr 41 (8): 827–31.
- Pathophysiology of Endocrine System - Prolactin at colostate.edu
- MedlinePlus Encyclopedia 003718
- eMedicine med/1098 - "Hyperprolactinemia"
- eMedicine med/1914 - "Prolactin Deficiency"
|Hormones and endocrine glands - edit|
Hypothalamus: - TRH - CRH - GnRH - GHRH - somatostatin - dopamine | Posterior pituitary: vasopressin - oxytocin - lipotropin | Anterior pituitary: GH - ACTH - TSH - LH - FSH - prolactin - MSH - endorphins - lipotropin
Thyroid: T3 and T4 - calcitonin | Parathyroid: PTH | Adrenal medulla: epinephrine - norepinephrine | Adrenal cortex: aldosterone - cortisol - DHEA | Pancreas: glucagon- insulin - somatostatin | Ovary: estradiol - progesterone - inhibin - activin | Testis: testosterone - AMH - inhibin | Pineal gland: melatonin | Kidney: renin - EPO - calcitriol - prostaglandin | Heart atrium: ANP
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