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. Prolactin is secreted from the pituitary gland and plays an essential role in metabolism, regulation of the immune system and pancreatic development. Discovered in non-human animals around 1930 by Oscar Riddle and confirmed in humans in 1970 by Henry Friesen, prolactin is a peptide hormone, encoded by the PRL gene. 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 cytokine-like manner and as an important regulator of the immune system. It has important cell cycle-related functions as a growth-, differentiating- and anti-apoptotic factor. As a growth factor, binding to cytokine-like receptors, it influences hematopoiesis and angiogenesis and is involved in the regulation of blood clotting through several pathways. The hormone acts in endocrine, autocrine, and paracrine manners through the prolactin receptor and numerous cytokine receptors. Pituitary prolactin secretion is regulated by endocrine neurons in the hypothalamus. The most important of these are the neurosecretory tuberoinfundibulum (TIDA) neurons of the arcuate nucleus that secrete dopamine (a.k.a. prolactin inhibitory hormone) to act on the D2 receptors of 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.
Function
In humans Prolactin has a wide variety of effects. It stimulates the mammary glands to produce milk (lactation): increased serum concentrations of prolactin during pregnancy cause enlargement of the mammary glands and prepare for milk production, which normally starts when levels of progesterone fall by the end of pregnancy and a suckling stimulus is present. Prolactin plays an important role in maternal behavior. 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. In general, dopamine inhibits prolactin but this process has feedback mechanisms. Elevated levels of prolactin decrease the levels of sex hormones—estrogen in women and testosterone in men. 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 gonadotropin although in humans it has only a weak luteotropic effect while the effect of suppressing classical gonadotropic hormones is more important. Prolactin within the normal reference ranges can act as a weak gonadotropin, but at the same time suppresses gonadotropin-releasing hormone secretion. The exact mechanism by which it inhibits gonadotropin-releasing hormone is poorly understood. Although expression of prolactin receptors have been demonstrated in rat hypothalamus, the same has not been observed in gonadotropin-releasing hormone neurons. Physiologic levels of prolactin in males enhance luteinizing hormone-receptors in Leydig cells, resulting in testosterone secretion, which leads to spermatogenesis. 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. Other actions include contributing to pulmonary surfactant synthesis of the fetal lungs at the end of the pregnancy and immune tolerance of the fetus by the maternal organism during pregnancy. Prolactin promotes neurogenesis in maternal and fetal brains. 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.
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