Prolactin (PRL) is also known as luteotropic hormone or luteotropin. It is a protein that is well-known for its role in allowing mammals (often females) to produce milk. It has influence in over 300 different processes in various vertebrates including humans. Prolactin is secreted from the pituitary gland in response to eating, mating, ovulation, nursing and estrogen treatment. Prolactin is often secreted in pulses in between these events. It also plays an important role in metabolism, pancreatic development and regulation of the immune system. It was first discovered in non-human animals around 1930 by Oscar Riddle. It was later confirmed in humans around 1970 by Henry Friesen.
Prolactin has a wide variety of effects such as stimulating the mammary glands to produce milk. An enlargement of the mammary glands that prepares it for milk production is caused by an Increase in serum concentrations of prolactin during pregnancy. This normally starts when levels of progesterone fall by the end of pregnant and a sucking stimulus is present.
Prolactin is produced at least in the anterior pituitary, decidua, breast, myometrium, lymphocytes, prostate and leukocytes in humans. A key regulator of prolactin production is estrogens that improve the growth of prolactin-producing cells. They also stimulate prolactin production directly and suppress dopamine. In decidual cells and lymphocytes, the distal promoter and prolactin expression is stimulated by cAMP (Cyclic adenosine monophosphate). Responsiveness to cAMP is mediated by an imperfect cAMP-responsive element and two CAAT/enhancer binding proteins (C/EBP). Progesterone upregulates prolactin synthesis in the endometrium and decreases it in myometrium and breast glandular tissue. Breast and other tissues can also express the Pit-1 promoter.
Structure and Isoforms
Prolactin structure is similar to growth hormone and placental lactogen. The molecule is folded due to the activity of three disulfide bonds. Significant heterogeneity of the molecule has been observed, thus bioassays and immunoassays can often give different results. This is caused by the differing glycosylation, sulfation, degradation and phosphorylation. The non-glycosylated form of prolactin secreted by the pituitary gland is the dominant form. There are three different sizes of prolactin:
● Little prolactin is the predominant form with a molecular weight of around 22-kDa. It is a single-chain polypeptide that contains 198 amino acids and is thought to be the result of removal of some amino acids.
● Big prolactin is approximately 48-kDA in weight and it is thought to be the product of interaction of several prolactin molecules. It appears to have slight biological activity.
● Big big prolactin is roughly 150-kDA in weight and is observed to have low biological activity