Prolactin

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Prolactin (PRL) is a peptide hormone primarily associated with lactation. In breastfeeding, the infant suckling the teat stimulates the production of prolactin, which fills the breast with milk (lactogenesis) in preparation for the next feed. Oxytocin, a similar hormone, is also released, which triggers milk let-down.

Production and regulation
It is synthesised and secreted by lactotrope cells in the adenohypophysis (anterior pituitary gland). It is also produced in other tissues including the breast and the decidua.

Pituitary prolactin secretion is regulated by neuroendocrine neurons in the hypothalamus, most importantly by neurosecretory dopamine neurons of the arcuate nucleus, which inhibit prolactin secretion. Thyrotropin-releasing factor 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.

Effects
"The major effect of increased prolactin is a decrease in normal levels of sex hormones — estrogen in women and testosterone in men."

Prolactin has many effects:


 * The most important of which is to stimulate 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.


 * Another effect, recently discovered by the University of Paisley and the ETH Zürich, is to provide the body with sexual gratification after sexual acts. The hormone represses the effect of dopamine, which is responsible for sexual arousal, thus causing 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 has been found to stimulate 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.


 * Other possible functions of prolactin include the surfactant synthesis of the fetal lungs at the end of the pregnancy and immune tolerance of the fetus by the maternal organism during pregnancy.

Variance in levels
There is a diurnal as well as an ovulatory cycle in prolactin secretion.

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 fibres 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.

Usually, in the absence of galactorrhea, lactation will cease within one or two weeks of the end of demand breastfeeding.

High prolactin levels also tend to suppress the ovulatory cycle by inhibiting the secretion of both FSH and GnRH.

Structure
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, while 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 are estrogens that enhances growth of  prolactin producing cells and  stimulates prolactin production directly as well as  suppressing dopamine.

Prolactin receptor

 * See prolactin receptor

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.

Conditions causing elevated prolactin secretion
Hyperprolactinaemia is the term given to having too-high levels of prolactin in the blood.


 * Prolactinoma;
 * Excess thyrotropin-releasing hormone (TRH), usually in primary hypothyroidism.
 * A side effect of many anti-psychotic medications

Conditions causing decreased prolactin

 * Bulimia;
 * Excess of dopamine.

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 only applies 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 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.