Prolactin (PRL)

Dr. Geoffrey Sher - August 5, 2021
Prolactin (PRL)

Prolactin (PRL) is a protein hormone (closely related to human growth hormone) that is secreted by specialized cells in the anterior part of the pituitary gland. In addition, the hormone is also produced and secreted by a broad range of other cells in the body, most prominently various immune cells, the brain, and the endometrium (lining of the uterus). Although prolactin’s major target organ is the mammary gland where it stimulates lactation, many organs can respond to prolactin…a not surprising finding given that most tissues contain cells demonstrating prolactin receptors. Lower animals such as mice cannot conceive without the presence of prolactin in the endometrium.  Human endometrium also produces prolactin in response to progesterone secretion from the ovary, and premature expression of both hormones seems to be linked to recurrent implantation failure.  Interestingly, immune cells are rich in prolactin receptors and certain types of lymphocytes actually synthesize and secrete prolactin. These observations suggest that prolactin may to some extent act as a regulator of the body’s immune activity. In an area in the brain known as the hypothalamus, a chemical called dopamine is released. Dopamine tonically suppresses prolactin synthesis and release by the pituitary gland. If this “hypothalamic brake set” is disturbed, prolactin levels will default to higher concentrations. Treatment with dopamine receptor agonists such as bromocriptine (Parlodel) and cabergoline (Dostinex), will re-establish prolactin suppression. Several other hypothalamic hormones, including thyroid releasing hormone (TRH) and gonadotropin releasing hormone (GnRH), can cause an increase in prolactin secretion.  Stimulation of the nipples (including but not limited to nursing) leads to hypothalamic activation and prolactin release. Estrogens also exerts a positive control over prolactin synthesis and secretion. Even modestly raised prolactin levels can interfere with estrogen-induced endometrial proliferation as well as egg/ ovarian follicle growth and development. Accordingly treatment with dopamine agonists would be of benefit in such cases. Increased PRL secretion reduces the pulsatility of hypothalamic GnRH, impairing the pituitary production of FSH and LH, and may directly impair the endocrine activity of ovarian follicles as well as endometrial response to estrogen. This can lead to dysfunctional or failed ovulation, a defective luteal phase, and a poorly developed endometrial response to estrogen (a thin endometrial lining). About 5% of unselected, asymptomatic infertile women have hyperprolactinemia. In such cases long-term use of dopaminergic drugs can normalize prolactin levels, leading to reestablishment of functional ovulation and improved endometrial development. About half of the pregnancies occurring during dopaminergic therapy start after the first 6 months of this drug therapy.  In addition, there is strong evidence to suggest that highly responsive IVF patients who are given oral cabergoline experience a significant reduction in the risk and severity of severe ovarian hyperstimulation syndrome (OHSS). This is thought to be due to cabergoline suppressing the production of vasoactive substances that are produced by luteinized follicular granulosa cells that remain after the egg retrieval. Hypothyroidism in women is often caused by an autoimmune process where antithyroid antibodies (ATA) progressively replace thyroid glandular tissue with functionless connective tissue. In roughly 50% of such cases there will be increased uterine natural killer cell activity (NKa) which can hinder implantation potential and progression.  Thus, ATA with NKa can be present prior to the development of clinically overt autoimmune hypothyroidism (Hashimoto’s disease). Since women with NKa are often infertile, or experience recurrent pregnancy loss, it is prudent to consider an immunologic evaluation in patients with unexplained hyperprolactinemia. What is not often commonly recognized is that even in cases where autoimmune hypothyroidism is clinically overt, treatment with thyroid hormone replacement will usually not solve the reproductive dysfunction which will usually require selective immunotherapy. Common manifestations of hyperprolactinemia:

  • In women:
    • Oligo/amenorrhea (reduction or absence of menstrual flow) and galactorrhea (excessive or spontaneous breast secretion of milk).
    • A modest elevation in blood prolactin can also point to an underlying state of hypothyroidism
  • In men: Such men rarely have galactorrhea
    • Hypogonadism,
    • Breast enlargement (gynecomastia)
    • Erectile dysfunction
    • Decreased Libido
    • Sperm dysfunction resulting in infertility and with impotence.

Causes of hyperprolactinemia: Main causes of pathologic hyperprolactinemia.

  • Pituitary adenoma
  • Renal Failure
  • Polycystic Ovarian Syndrome (PCOS)
  • Certain drugs:
    • Antipsychotic drugs ( phenothiazines, haloperidol, monoamine oxidases (MAO) risperidone, fluoxetine, butyrophenones,
    • Anti-emetics: metoclopramide, domperidone,
    • Tricyclic antidepressants
    • Opiates
    • Verapamil
    • Antihypertensives and Ganglion blockers
  • Hypothyroidism. Lower than normal levels of thyroxine (thyroid hormone) induces the hypothalamus to increase output of thyroid releasing hormone (TRH). TRH has a  stimulatory effect on the prolactin secreting cells of (lactotroph) cells of the pituitary, so a mild increase in prolactin (PRL) levels can occur. In these cases, replacing thyroid hormone might be sufficient to correct the prolactin levels.

   


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