Introduction
Prolactin stimulates the proliferation and differentiation of mammary gland cells necessary for lactation. In humans, the main symptoms associated with prolactin, such as hypogonadism and infertility, are the result of hypersecretion of this hormone.
The prolactin receptor (PRL-R) is expressed ubiquitously, but there is also tissue-specific variability in expression patterns.
Animal model studies attribute several functions to prolactin, both physiological (reproduction, lactation, growth, metabolism, electrolyte transport, and behavior) and pathological (immunity and carcinogenesis).
Over the past decade, many new insights into the functions of prolactin and its receptor have emerged, including the identification of the first inactivating mutation in the human gene encoding PRL-R, PRLR, and the mechanism by which high prolactin levels can lead to gonadotropin deficiency and infertility.
Discovery
Prolactin and growth hormone, along with placental lactogens, form a family of hormones likely resulting from the duplication of an ancestral gene.
In the early 20th century, histological changes in the anterior pituitary of pregnant women were first noted. French researchers were the first to identify a pituitary factor capable of inducing milk secretion in rabbits.
American scientists made similar observations and, in addition to naming the new pituitary factor prolactin, showed that prolactin could stimulate the growth of the pigeon crop sac.
It was shown that prolactin is present in the blood of all vertebrates studied to date.
Biological Role of Prolactin
Prolactin was first isolated in rabbits. Researchers discovered its ability to stimulate mammary gland development and lactation. Shortly thereafter, it was found that the hormone could stimulate the production of crop milk in pigeons.
Animal models provided insights into the biology of prolactin proteins and offer compelling evidence that each prolactin isoform has independent biological functions.
The primary isoform of prolactin, with a molecular weight of 23 kDa, acts through its membrane receptor, the prolactin receptor (PRL-R), which is a member of the hematopoietic cytokine superfamily.
The 16 kDa isoform of prolactin is a cleavage product derived from native prolactin, which has attracted particular attention due to its recently described inhibitory effects on angiogenesis and oncogenesis.
Prolactin is synthesized by the anterior pituitary gland, extrapituitary tissues such as the mammary gland, prostate, skin, and brain. During lactation, the hormone promotes the synthesis of milk and colostrum, while oxytocin stimulates its secretion.
The discovery of multiple extrapituitary sites of prolactin secretion also expands the range of known functions of this hormone.
Prolactin is associated not only with lactogenesis but also with a wide range of other functions in various tissues, modulating neurogenesis, nervous system development, sleep, learning, memory, and immune system homeostasis. Additionally, it may be linked to various types of cancer.
It also regulates reproductive function, electrolyte balance, glucose and lipid metabolism, affecting numerous processes of energy homeostasis.
Lactation
As mentioned above, prolactin is a polypeptide hormone with a molecular weight of 23 kDa, synthesized by the anterior pituitary gland. During lactation, prolactin promotes milk synthesis, while oxytocin stimulates milk secretion.
During the first trimester of pregnancy, the duct system expands and branches in response to rising estrogen levels, which also stimulate the pituitary gland to produce prolactin, which around the 20th week of pregnancy stimulates the mammary glands to produce milk.
Post-lactational involution occurs when milk production ceases due to decreased prolactin levels. Dopamine and GABA (gamma-aminobutyric acid) inhibit prolactin secretion, while TRH (thyrotropin-releasing hormone) stimulates its synthesis.
Prolactin, Immunity, and Homeostasis
The primary isoform of prolactin, with a molecular weight of 23 kDa, acts through its membrane receptor, the prolactin receptor (PRL-R), which is a member of the hematopoietic cytokine superfamily, and its activation mechanism has been deciphered.
The relationship between prolactin and the immune system has opened new perspectives in immunoendocrinology, highlighting its important role in innate and adaptive immune responses.
Prolactin has bioactive functions, acting as both a hormone and a cytokine. It influences the modulation of the immune system, primarily by inhibiting the negative selection of autoreactive B-lymphocytes.
The significant asymmetry of autoimmune diseases between sexes is one of the most intriguing phenomena in the mosaic of autoimmunity. It is believed that sex hormones play a crucial role in this dimorphism. There is substantial evidence linking prolactin to the immune system through cytokines such as interleukins.
In cases of systemic lupus erythematosus and rheumatoid arthritis, patients may exhibit elevated prolactin levels.
Both hypoprolactinemia and hyperprolactinemia imply immunological damage, and immunosuppression or the development of autoimmunity may occur.
Studying the connection between this hormone and the immune system could become a focus of future research.
Prolactin and Oncology
This hormone appears to play a certain role in regulating tumorigenesis, particularly in breast and prostate cancer. Prolactinomas account for about 40% of all pituitary tumors and are microadenomas in 95% of cases, with a prevalence of 6 to 50 per 100,000 adults.
It has been found that prolactin, involved in the normal development of the mammary gland and lactation, plays a significant role in the etiology of breast cancer, as it can promote cell proliferation and survival, increase cell mobility, and support tumor vascularization.
However, the link between prolactin and cancer development has long ceased to be an exclusively female issue. The physiological role of prolactin for the prostate is not fully understood, but a substantial body of evidence indicates its important role in prostate oncogenesis.
Prostate and breast cancers, affecting millions of men and women respectively, are treated by modern medicine using various methods to counteract the prolactin receptor (PRLR) and its signaling pathways, which include small-molecule and protein antagonists.
Pathology
Increased prolactin concentration in the blood is called hyperprolactinemia, and decreased concentration is called hypoprolactinemia.
Elevated prolactin levels are observed in prolactinoma — a benign tumor (adenoma) of the pituitary gland. Additionally, hypersecretion can lead to pathological conditions such as galactorrhea and amenorrhea.
