Prolactin: Sex and Immune Activation

The hormone prolactin does a great deal more than just induce lactation in women who are breastfeeding babies. Yet it seems to be somewhat ignored as a major regulator of processes involved in autoimmune diseases and of orgasm and sexual function in both men and women.

The production of orgasm, either by masturbation or coitus, results in a large release of prolactin immediately afterward, which remains elevated for about one hour.1 Sexual arousal alone induces no changes in prolactin in either men or women. Hyperprolactinemia, where prolactin levels are higher than normal, leads to suppression of libido and to sexual dysfunction in both men and women. We interpret this effect of high prolactin levels as similar to the refractory period following sex. Prolactin levels go up after orgasm but then, over about an hour, return to normal. During the postorgasmic period, there are high prolactin levels and loss of libido and sexual function until prolactin levels return to normal. If “normal” levels are already high, however, there may never be an end to the refractory period.

A commonly used dopaminergic agonist (treatment for Parkinson’s disease), bromocriptine (Parlodel®), is very effective in normalizing hyperprolactinemia. We have been using it for over 25 years as an anti-aging drug because keeping prolactin levels down is also known to maintain the sensitivity of the tuberoinfundibular dopamine neurons, the brain area that responds to prolactin.1 Another drug, carbergoline, is also available for normalizing hyperprolactinemia. However, we like bromocriptine because it has been used for a very long time by many millions of people, and any possible negative effects would have long since shown up.

One unfortunate effect of the SSRI (selective serotonin receptor inhibitor) antidepressant drugs is that they are considered to be “. . . the primary producer of drug-induced hyperprolactinemia, although no research has accurately described the prevalence of this phenomenon.”2 Another study3 found that oral administration of 200 mg of 5-hydroxytryptophan (5-HTP) in 18 of 21 normal subjects significantly increased plasma prolactin levels.

Excess amounts of prolactin could also be a hazard because prolactin is known to play a major role in the growth of certain tissues (breast, prostate4).

Prolactin plays a role in autoimmune diseases by stimulating autoimmune B cells. For example, systemic lupus erythematosus (SLE) can be a very severe, even fatal, autoimmune disease with autoreactive B cells attacking every organ in the body, DNA, etc. Small-scale trials with SLE patients being treated with bromocriptine have suggested a beneficial effect in mild and moderate disease activity. Recent studies in female NZB/WF1 lupus-prone mice demonstrated that hyperprolactinemia accelerated disease and decreased survival, while bromocriptine increased survival.5 Scientists have found that estradiol blocks the deletion of naive autoreactive B cells that arise in the bone marrow. Estrogen increases prolactin secretion, and B cells express prolactin receptors.5 Another paper6 reports that the inflammatory cytokine IL-6 gene expression is high in lupus and that IL-6 has been reported to stimulate prolactin release from cultured rat pituitary cells.

Besides bromocriptine, it has been reported that cholinergic stimulation by systemic or intracerebroventricular (professional driver—closed course—don’t try this at home) administration causes a decrease in serum prolactin concentration.7 Other studies have found cholinergic drugs to inhibit prolactin secretion and tumor necrosis factor.8,9Increased cholinergic neuronal activity can be achieved by taking supplemental choline and vitamin B5, acetylcholinesterase inhibitors (such as galantamine), and N-acetylcarnitine. Prolactin increases with age; much of this may be due to the damage that takes place in the dopaminergic and cholinergic nervous systems, which suppress prolactin release. In one study, researchers found that, in healthy subjects between the ages of 60 and 85 years (as compared to healthy individuals between the ages of 20 and 40 years), only 16% of ingested choline was taken up by the brain through the blood-brain barrier, even though there was a similar increase in plasma choline concentration in both younger and older subjects.10

Also, another reason to get rid of excess fat is that adipocytes (fat cells) release leptin, a hormone that can exert a stimulatory effect on steroid-induced or spontaneous prolactin.7

References

  1. MohanKumar et al. Effects of chronic bromocriptine treatment on tyrosine hydroxylase (TH) mRNA expression, TH activity, and median eminence dopamine concentrations in ageing rats. J Neuroendocrinol 13:261-9 (2001).
  2. Kruger et al. Orgasm-induced prolactin secretion: feedback control of sexual drive? Neurosci Biobehav Rev 26:31-44 (2002).
  3. Kato et al. Effect of 5-hydroxytryptophan (5-HTP) on plasma prolactin levels in man. J Clin Endocrinol Metab 38:695-7 (1974).
  4. Wennbo et al. Transgenic mice overexpressing the prolactin gene develop dramatic enlargement of the prostate gland. Endocrinol 138:4410-15 (1997).
  5. Peeva et al. Bromocriptine restores tolerance in estrogen-treated mice. J Clin Invest 106(11):1373-9 (2000).
  6. Walker et al. Prolactin and autoimmune disease. Trends Endocrinol Metab4:147-151 (1993).
  7. Freeman et al. Prolactin: structure, function, and regulation of secretion. Physiol Rev 80(4):1523-1631 (2000).
  8. Grandison et al. Inhibition of prolactin secretion by cholinergic drugs. Proc Soc Exp Biol Med 145:1236-9 (1974).
  9. Wang et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384-8 (2003).
  10. Cohen et al. Decreased brain choline uptake in older adults. JAMA 274(11):902-7 (1995).