Physiology of Prolactin

Prolactin Origins, Relation to HGH, and its Central Role: Lactation

Prolactin is primarily a female hormone that plays a central role in facilitating lactation and plays a large role in reproductive success. However, important roles in non-pregnant women and in men have been discovered as well. Nevertheless, Prolactin has been dubbed the “hormone of maternity”[1]. Prolactin itself has a very interesting evolutionary history and relation to other hormones in the body. As previously mentioned in the introduction of this article, Prolactin is a hormone secreted from the anterior pituitary gland. As such, Prolactin is a hormone of the pituitary. As is common knowledge, HGH (Human Growth Hormone), otherwise properly known as Somatotropin, is also a pituitary hormone and perhaps the most commonly known one. HGH is a pituitary hormone that expresses generalized growth promotion in the body, and Prolactin is a growth hormone that expresses more specific growth promotion (on the mammary glands). The point that is being lead to here is that HGH and Prolactin both belong to a family of hormones known as the Somatotropin family of protein hormones. This family includes: HGH, Prolactin, Choriomammotropin (Lactogen), Proliferin, and a few others depending on the organism(s) in question. These are all hormones of the pituitary gland, and are all growth hormones that exhibit different growth activity in one form or another throughout the body in different tissues. This might possibly be a perfect explanation as to why many HGH secretagogues and peptides result in a potential increase in Prolactin as well as HGH.

HGH and Prolactin in particular are two hormones that are extremely identical in structure and amino acid sequence, and the two are evolutionarily homologous, suggesting that they originate from an ancient progenitor molecule that originally developed early in the evolution of vertebrates. Two researchers in 1928, Stricker and Grueter, stumbled across the discovery that an extract from the pituitary gland when injected into rabbits could stimulate the secretion of milk[2]. It should be understood, however, that the development of mammary glands and the stimulation of milk secretion are very complicated processes that require a combination of a plethora of different hormones, including: Estrogen, Prolactin, insulin, glucocorticoids, HGH, placental lactogen, relaxin, and Progesterone[3]. Lactation is facilitated by Prolactin via its action on the plasmalemmal receptors of mammary gland alveolar secretory cells[4] [5]. There is normally an increase in the proliferation of Prolactin receptors that is synchronous with the onset of lactation, which tends to happen at the same time as a major rise in serum prolactin levels occurs[6]. Estradiol (E2) serves to actually increase this proliferation of mammary gland Prolactin receptors, while Progesterone acts to suppress this increase, and Prolactin also serves to up-regulate its own receptors[7]. Although the lactation process and the causes behind it ultimately become more complex (involving more hormones, and specific cellular activity), this is the central core of hormonal action for it. Genetic factors do play a role in how predisposed an individual is to developing gynecomastia and/or lactation if all of the hormonal factors are set in proper position.

Adding to these details, Estrogen seems to stimulate the secretion of Prolactin at the anterior pituitary gland[8], as evidenced also by the fact that Prolactin production by the lactotrophs at the pituitary gland increases dramatically during pregnancy, causing serum Prolactin levels to significantly increase. Infusions of Estrogen also stimulate Prolactin synthesis via direct activity on Prolactin gene transcription[9].


Role and Effects of Prolactin in Men, and Prolactin Side Effects

Considering the fact that Prolactin serves a major purpose in facilitating lactation, there is plenty of evidence to support the fact that Prolactin may possibly exhibit effects on testicular function[10]. For example, in rats, inhibition of Prolactin secretion from the pituitary is associated with a drop in testicular LH (Luteinizing Hormone) receptors, demonstrating that Prolactin might possibly be vital to the maintenance of LH receptor proliferation in the testes. However, this seems to be a case of “too much or too little”, as an excess of Prolactin has demonstrated to result in hypogonadism[11]. In addition to this, although Prolactin can act as a mild gonadotropin through increasing the number of LH receptors, it has been found to inhibit GnRH (gonadotropin releasing hormone) secretion[12].

The most interesting effect of Prolactin for males is its documented effects on sex drive and the male orgasm. Although still not completely understood, the male orgasm and the refractory period is affected significantly by Prolactin. It has been discovered that following a male orgasm, Prolactin levels naturally increase quite significantly, which is believed to contribute to the refractory period after sexual activity and orgasm (in both males and females)[13]. The evidence seems to demonstrate that Prolactin in males serves as a negative feedback mechanism following orgasm, which signals the central nervous system (CNS) in controlling sexual arousal and sexual behavior. As such, it has been discovered that by either increasing hormones/molecules that are antagonistic to Prolactin (such as dopamine) or by activating D2 dopamine receptors with a dopamine agonist, the refractory period can be significantly reduced as well as increasing the intensity of the male orgasm[14] [15]. Conversely, chronic and significant elevations of Prolactin levels lead to the inhibition of sexual behavior, drive, and even the loss of the ability to achieve orgasm (anorgasmia)[16]. This has also been observed in hyperprolactinaemic patients that must be treated with dopamine agonists in order to reduce chronic elevations of Prolactin.

Of course, as would be expected from a hormone such as Prolactin rising to excessive levels, men would also have a high probability of experiencing the most typical of all Prolactin side effects: lactation from the nipples. Though this lactation is not what would be typical of a childbearing woman, the lactation experienced by men is often minor to moderate in nature, and the fluid discharge is normally clear rather than white. Furthermore, most lactation would normally occur as a result of a physical stimulus such as pressure, squeezing, or a suckling motion on the nipples. More severe cases are accompanied by a puffiness/growth of the nipple area comprised of the areola and the nipple itself forming a ‘pointy’ puffiness. Though this is normally not the same type of mammary formation as gynecomastia (which is characterized by glandular tissue forming in the chest area around the nipple in general, it can also be accompanied with full-blown gynecomastia (and often is, considering the importance that Estrogen has in mammary growth, glandular formation, and lactation as mentioned earlier).

Normal Physiological Range of Prolactin

As Prolactin is a necessary hormone in all of us just like any other hormones we manufacture, there is an ideal range that Prolactin should be in. Just as how Prolactin levels should not be too high, they should not be too low either. The following are general markers for where an individual should ideally be after bloodwork has been done.

Generally speaking, males should be in the range of 5 – 15 µg/L. Non-pregnant females should be in the range of 5 – 25 µg/L, and pregnant females in the range of 35 – 385 5 µg/L.


Medical References:

[1] Hadley M, Levine J. 2006. Endocrinology. 6th ed. Toronto: Pearson Education, pp. 100.

[2] Stricker P, Grueter R. (1928) C. R. Soc. Biol. 99, 1978–1980.

[3] Neville MC, McFadden TB, Forsyth I.2002. Hormonal regulation of mammary differentiation and milk secretion. J Mammary Gland Biol Neoplasia. 2002 Jan;7(1):49-66.

[4] Goffin V, Binart N, Touraine P, Kelly PA. 2002. Prolactin: the new biology of an old hormone. Annu Rev Physiol. 2002;64:47-67.

[5] Ormandy CJ, Sutherland RL. 1993. Mechanisms of prolactin receptor regulation in mammary gland. Mol Cell Endocrinol. 1993 Feb;91(1-2):C1-6.

[6] Hadley M, Levine J. 2006. Endocrinology. 6th ed. Toronto: Pearson Education, pp. 445.

[7] Hadley M, Levine J. 2006. Endocrinology. 6th ed. Toronto: Pearson Education, pp. 445.

[8] Sengupta A, Sarkar DK. 2012. Estrogen inhibits D2S receptor-regulated Gi3 and Gs protein interactions to stimulate prolactin production and cell proliferation in lactotropic cells. J Endocrinol. 2012 Jul;214(1):67-78. doi: 10.1530/JOE-12-0125. Epub 2012 May 9.

[9] Maeda T, Ikegami H, Sakata M, Yamaguchi M, Wada K, Koike K, Adachi K, Kurachi H, Hirota K, Miyake A. 1996. Intraventricular administration of estradiol modulates rat prolactin secretion and synthesis. J Endocrinol Invest. 1996 Oct;19(9):586-92.

[10] Hadley M, Levine J. 2006. Endocrinology. 6th ed. Toronto: Pearson Education, pp. 101.

[11] Breves JP, McCormick SD, Karlstrom RO. 2014. Prolactin and teleost ionocytes: New insights into cellular and molecular targets of prolactin in vertebrate epithelia. Gen Comp Endocrinol. 2014 Jan 13. pii: S0016-6480(14)00002-1. doi: 10.1016/j.ygcen.2013.12.014. [Epub ahead of print]

[12] Grattan DR, Jasoni CL, Liu X, Anderson GM, Herbison AE (September 2007). “Prolactin regulation of gonadotropin-releasing hormone neurons to suppress luteinizing hormone secretion in mice”. Endocrinology 148 (9): 4344–51. doi:10.1210/en.2007-0403. PMID 17569755.

[13] Krüger TH, Haake P, Hartmann U, Schedlowski M, Exton MS. 2002. Orgasm-induced prolactin secretion: feedback control of sexual drive? Neurosci Biobehav Rev. 2002 Jan;26(1):31-44.

[14] Krüger TH, Haake P, Haverkamp J, Krämer M, Exton MS, Saller B, Leygraf N, Hartmann U, Schedlowski M. 2003. Effects of acute prolactin manipulation on sexual drive and function in males. J Endocrinol. 2003 Dec;179(3):357-65.

[15] Levin RJ. Revisiting post-ejaculation refractory time-what we know and what we do not know in males and in females. J Sex Med. 2009 Sep;6(9):2376-89. doi: 10.1111/j.1743-6109.2009.01350.x. Epub 2009 Jun 9.

[16] Krüger TH, Hartmann U, Schedlowski M. 2005. Prolactinergic and dopaminergic mechanisms underlying sexual arousal and orgasm in humans. World J Urol. 2005 Jun;23(2):130-8. Epub 2005 May 12.