Physiology of Prolactin
The origins of prolactin, its relationship with HGH, and its central role in the body.
Prolactin is a female hormone that plays a central role in reproductive success, primarily in promoting lactation.
However, it has also been found to play an important role in non-pregnant women and men.
Despite this, prolactin is often referred to as the "fertility hormone" [1].
Prolactin itself has a very interesting evolutionary history and relationship with other hormones in the body.
As mentioned in the introduction to this article, prolactin is a hormone secreted by the anterior pituitary gland.
Therefore, prolactin is a pituitary hormone.
Human growth hormone (HGH), more commonly known as somatotropin, is also a pituitary hormone and probably the most commonly known.
HGH is a pituitary hormone that has a general growth-promoting action in the body, while prolactin is a growth hormone that has a more specific growth-promoting action (in the mammary gland).
The important thing to note here is that both HGH and prolactin belong to a family of hormones known as the somatotropin family of protein hormones.
This family includes
HGH, prolactin, chorionic milk secretagogue (lactogen), proliferin, and a few other hormones depending on the organism in question.
These are all growth hormones that are secreted by the pituitary gland, and each tissue in the body exhibits different growth activity in some form or another.
This could be a perfect explanation for why many HGH secretagogues and peptides result in a potential increase in prolactin and HGH.
In particular, HGH and prolactin are two hormones with very similar structures and amino acid sequences, and their evolutionary homology suggests that they may have originated from an ancient ancestral molecule that developed early in the evolution of vertebrates.
In 1928, two researchers, Stricker and Grueter, accidentally discovered that injecting pituitary gland extracts into rabbits could stimulate milk secretion [2].
However, it is important to understand that mammary gland development and stimulation of milk secretion is a very complex process that requires a combination of different hormones, including Estrogen, prolactin, insulin, glucocorticoids, HGH, placental lactogen, relaxin, and progesterone [3].
Prolactin promotes lactation through its action on the protoplasmic receptors of mammary alveolar secretory cells [4] [5].
Proliferation of prolactin receptors typically increases at the onset of lactation, which tends to coincide with a significant rise in serum prolactin levels [6].
Estradiol (E2) actually acts to increase this proliferation of mammary prolactin receptors, while progesterone acts to inhibit this increase, and prolactin also acts to upregulate its own receptors [7].
The process of lactation and its causes are ultimately more complex, involving many more hormones and specific cellular activities, but this is the essence of hormonal action on lactation.
When all the hormonal factors are in the right place, genetic factors influence an individual's propensity for gynecomastia and/or lactation.
Adding to these details, estrogen appears to stimulate prolactin secretion from the anterior pituitary [8], as evidenced by the fact that during pregnancy, prolactin production by the pituitary's lactotrophs increases dramatically, resulting in a significant increase in serum prolactin levels.
Estrogen infusion also stimulates prolactin synthesis through direct activity on prolactin gene transcription [9].
The Role and Effects of Prolactin in Men and Prolactin Side Effects
Given the important role prolactin plays in promoting lactation, there is a large body of evidence to support the idea that prolactin can affect testicular function [10].
For example, in rats, suppression of prolactin secretion from the pituitary gland is associated with a decrease in testicular LH (luteinizing hormone) receptors, demonstrating that prolactin may be essential for maintaining LH receptor proliferation in the testes. However, this appears to be a case of "too much or too little", as an excess of prolactin has been proven to cause hypogonadism [11].
In addition to this, prolactin can act as a mild gonadotropin by increasing the number of LH receptors, but it has also been found to inhibit GnRH (gonadotropin-releasing hormone) secretion [12].
The most interesting effect of prolactin in men is its effect on libido and male orgasm.
Although not yet fully understood, male orgasm and refractory periods are strongly influenced by prolactin.
After a male orgasm, prolactin levels naturally increase quite significantly, and this is believed to contribute to sexual activity and the post-orgasmic refractory period (in both men and women) [13].
This evidence seems to indicate that prolactin in men acts as a negative feedback mechanism in the post-orgasmic central nervous system (CNS) to regulate sexual arousal and sexual behavior.
Therefore, it has been found that increasing hormones/molecules that antagonize prolactin, such as dopamine, or activating D2 dopamine receptors with dopamine agonists, can not only increase the intensity of male orgasms, but also significantly reduce the duration of refractoriness [14] [15]. Conversely, chronic and markedly elevated prolactin levels lead to a loss of sexual activity, suppressed libido, and even the ability to achieve orgasm (anorgasmia) [16].
This phenomenon has also been observed in patients with hyperprolactinemia who need to be treated with dopamine agonists to reduce the chronic elevation of prolactin.
Of course, as you might expect when a hormone like prolactin rises to excessive levels, men are more likely to experience nipple lactation, which is the most typical symptom of prolactin side effects.
While these lactations are different from the typical lactations seen in women of childbearing age, the lactations seen in men are usually mild to moderate, and the discharge is usually a clear liquid rather than white.
In addition, most lactation occurs as a result of physical stimulation, such as compression or squeezing of the nipple or sucking motions.
In more severe cases, the nipple area, which consists of the areola and the nipple itself, swells or grows to form a 'pinnate' swelling.
This is not the same type of breast development as gynecomastia, which is typically characterized by the formation of glandular tissue in the chest area around the nipple, but as mentioned earlier, it can also accompany full-blown gynecomastia given the importance of estrogen on breast growth, glandular formation, and lactation.
Normal physiologic range for prolactin
Because prolactin is a hormone that your body needs, just like any other hormone, there is an ideal range that prolactin should be in.
Just as prolactin levels shouldn't be too high, they shouldn't be too low either.
The following are general indicators of the levels an individual should ideally maintain after a blood test.
In general, men should be in the range of 5 - 15 µg/L.
Non-pregnant women should be in the range of 5 - 25 µg/L and pregnant women should be 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) CR 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 the mammary gland. Mol Cell Endocrinol. February 1993;91(1-2):C1-6.
[6] Hadley M, Levine J. 2006. Endocrinology. 6th ed. Toronto: Pearson Education, 445 pp.
[7] Hadley M, Levine J. 2006. Endocrinology. 6th ed. Toronto: Pearson Education, p. 445.
[8] Sengupta A, Sarkar DK. 2012. Estrogen stimulates prolactin production and cell proliferation in miscarriage-promoting cells by inhibiting D2S receptor-regulated Gi3 and Gs protein interactions. J Endocrinol. 2012 Jul;214(1):67-78. doi: 10.1530/JOE-12-0125. Epub May 9, 2012.
[9] Maeda T, Ikegami H, Sakata M, Yamaguchi M, Wada K, Koike K, Adachi K, Kurachi H, Hirota K, Miyake A. 1996. Intracerebroventricular 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 the 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 modulation 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: a feedback regulation of sexual desire? 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 desire and function in men. J Endocrinol. December 2003;179(3):357-65.
[15] Levine RJ. Post-ejaculatory refractory time revisited - what we know and don't know in men and women. J Sex Med. 2009 Sep 6(9):2376-89. doi: 10.1111/j.1743-6109.2009.01350.x. Epub June 9, 2009.
[16] Krüger TH, Hartmann U, Schedlowski M. 2005. Prolactinergic and dopaminergic mechanisms underlying human sexual arousal and orgasm. World J Urol. June 23, 2005; 23(2):130-8. Epub May 12, 2005.
