Article: Prolactin

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Prolactin
Identifiers
Symbol(s)	PRL
Entrez	5617
OMIM	176760
RefSeq	NM_000948
UniProt	P01236
PDB	{{{PDB}}}
Other data
EC number	[1]
Locus	Chr. 6 p22.2-p21.3

Prolactin is a peptide hormone 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.

Effects

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 Technische Hochschule 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 male's refractory period. The amount of prolactin can be an indicator for the amount of sexual satisfaction and relaxation. Unusual high amounts are suspected to be responsible for impotence.

Other possible functions of prolactin include the surfactant synthesis of the foetal lungs at the end of the pregnancy and immune tolerance of the foetus 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

The prolactin receptor - encoded by a gene on Chromosome 5p13-14 - interacts with the prolactin molecule as a transmembrane receptor. Thus it contains an extracellular region that binds prolactin, a transmembrane regions, and a cytoplasmatic region. A specific second messenger has not yet been identified. There may be variations among different tissue prolactin receptors.

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.

Conditions causing elevated prolactin secretion

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

• Prolactinoma
• Hypothyroidism

Conditions causing decreased prolactin

• Bulimia
• Excess of dopamine

Use of breastfeeding as contraceptive

As a contraceptive, demand breastfeeding is said to be more than 90% effective in the first month of post-partum even if no other forms of contraception are used, with decreasing effectiveness in successive months. 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 90% effectiveness only applies if three criteria are met:

• 1. The mother has no 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, fertility returns to normal. It is not advised, however, to rely on this method as the only contraceptive for any long period of time.

See also

• weaning
• breast feeding
• baby food
• male lactation
• hormones