What is PRL (Prolactin)?
PRL (prolactin) is a peptide hormone secreted primarily by lactotroph cells of the anterior pituitary gland, whose main physiological function is to initiate and maintain lactation, though it also plays important roles in reproduction, immune regulation, and osmoregulation. 1, 2
Basic Physiology
Prolactin is a member of a hormone family that includes growth hormone (GH) and placental lactogens (PLs), likely derived from duplication of an ancestral gene. 3
The hormone acts through the prolactin receptor (PRLR), which belongs to the cytokine class-1 receptor superfamily and is widely distributed throughout the body—making it difficult to find a tissue that doesn't express PRLR mRNA or protein. 3
PRL secretion is primarily regulated by negative control from the hypothalamus, with dopamine serving as the major physiologic prolactin-inhibiting factor (PIF). 4
Prolactin-releasing factors include thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP), and oxytocin, all of which have prolactin-releasing activity. 4
Regulation and Normal Levels
Prolactin secretion is induced by sleep, stress, sexual intercourse, and suckling stimulus. 4
Serum prolactin levels are increased by estrogen, resulting in higher levels in women compared to men, particularly during the late follicular phase and pregnancy. 4
Normal serum prolactin levels vary by sex and age, with typical reference ranges being approximately <20 μg/L (or <425 mU/L) for non-pregnant adults, though specific laboratory reference ranges should be used as values differ by assay method. 5
Prolactin levels are highest in the first 2 years of life, decrease in mid-childhood, and rise again in adolescence with higher levels in girls than boys. 5, 6
Biological Functions
Lactation is the major and most well-established biological function of prolactin in humans and is essential to reproduction. 1, 4
More than 300 separate actions of prolactin have been reported in various vertebrates, including effects on water and salt balance, growth and development, endocrinology and metabolism, brain and behavior, reproduction, and immune regulation and protection. 3
A large proportion of prolactin's actions are directly or indirectly associated with reproduction, including many behavioral effects. 3
Prolactin is an important regulator of immune function, with disease states including various cancers and autoimmune diseases appearing related to prolactin overproduction acting in endocrine, autocrine, or paracrine manner. 3
In the context of reproduction, prolactin regulates the hypothalamic-pituitary-ovarian axis, influencing maturation of ovarian follicles and ovulation. 7
Mechanism of Action
Prolactin binds to cell surface receptors in a two-step process: site 1 on PRL binds to one receptor molecule, then a second receptor molecule binds to site 2 on the hormone, forming a homodimer of one PRL molecule and two receptor molecules. 3
The PRLR contains no intrinsic tyrosine kinase cytoplasmic domain but associates with cytoplasmic tyrosine kinase JAK2, which becomes phosphorylated and activated upon receptor dimerization. 3
Major signaling pathways include phosphorylation of cytoplasmic STAT proteins (which dimerize, translocate to the nucleus, and bind to specific promoter elements on PRL-responsive genes) and activation of the Ras/Raf/MAP kinase pathway involved in proliferative effects. 3
Clinical Significance
Pathological hyperprolactinemia most commonly presents as an ovulatory disorder and is often associated with secondary amenorrhea or oligomenorrhea. 1
Hyperprolactinemia produces reproductive dysfunction in both sexes, resulting in hypogonadism, infertility, and galactorrhea, though it may also be asymptomatic. 2
Hyperprolactinemia inhibits secretion of gonadotropins through inhibition of the hypothalamic kisspeptin hormone, leading to hypogonadism. 5
Prolactinomas (lactotroph adenomas) are one of the most common causes of prolactin excess, representing approximately 40% of all pituitary tumors. 2
In the context of stereotactic radiosurgery for secretory pituitary adenomas, prolactinomas show crude tumor control rates of 93% (95% CI 90.0%–95.0%), crude endocrine remission rates of 28% (95% CI 19.0%–39.0%), and any new hypopituitarism rates of 12% (95% CI 6.0%–24.0%). 8