Preface

Prolactin is a polypeptide hormone that is synthesized in and secreted from the lactotrophs of the anterior pituitary gland. The name of the hormone was originally given 80 years ago based on the fact that bovine pituitary extract causes growth of the crop sac and stimulate the elaboration of crop milk in pigeons[1]. Nowadays, we already know that prolactin plays multiple pivotal roles in control of general homeostasis[2-5]. Without giving a detailed list, rather some of them will be highlighted here. The classical role can be seen in mammals where prolactin stimulates the mammary glands to produce milk during lactation and the development of corpus luteum of the ovary to secrete its hormone i.e. progesterone.

Its osmoregulatory role is also well defined. It has a critical role in fish, so it is also called a "freshwater-adapting" hormone[6]. Plasma prolactin levels may follow the changes of environmental milieu, i.e. be lower in seawater fish, but increased in freshwater.

During the last two decades we have learned that prolactin has a prominent and well defined role in the regulation of immune function[7,8]: as an immune modulator it enhances the proliferative response, but also has a role in certain autoimmune diseases as a pathoclinical indicator in multi-organ and organ specific autoimmune diseases (e.g. in lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome, Hashimoto's thyroiditis, multiple sclerosis (MS), psoriasis, etc)[9, 10, 11]. Prolactin may also participate in the development of immune tolerance between the fetus and the maternal organism during pregnancy[12]. Several experimental and also clinical evidences confirming the relationship between prolactin and the immune system have required to open new "sub-folder" for the role of prolactin in "immune-biology", "immuneendocrinology" and "neuroimmune-modulation", as well as for non-clinical and clinical contributions to the search for potential new drugs in the development process.

The physiological role of prolactin is still important in the classical fields of reproduction. Prolactin seems to be involved in the central control of sexual behavior and activity. There is a brief and sudden elevation of prolactin during orgasm indicating that it may have a role in the "gratification" during sexual acts as well[13]. On the other hand, a nondrug related female sexual dysfunction (FSD), affecting up to 1 in 10 US women, manifested with a decreased sexual desire could also be associated X Preface

with increased prolactin levels [14]. A chronic hyperprolactinemia is clinically associated with hypogonadotropic hypogonadism and sexual dysfunction as well, while treatment of hyperprolactinemia restores normal sexual function both in men and women[15].

Moreover, prolactin levels and our behavior are potentially also connected. Prolactin is higher during periods of nursing in some species, but also in human during "maternal" as well as "paternal" behavior: fathers of infants have elevated prolactin levels [16].

Prolactin stimulates proliferation of oligodendrocyte precursor cells (they are cells that differentiate into oligodendrocytes, and they are responsible for the formation of myelin sheet of axons in the central nervous system (CNS)[17,18]. Interestingly, high prolactin levels stimulate the proliferation of olfactory epithelium[19].

Prolactin can also be found in amniotic fluid and contributes to surfactant synthesis of fetal lungs at the end of pregnancy[20].

Since pituitary prolactin is under a close and mainly inhibitory control of hypothalamic dopaminergic system, it is predictable that drugs attenuating pathological neurotransmitter levels (like in schizophrenia, mood disturbances, etc) may have potential side effect resulting in clinical signs associated with or caused by hyperprolactinemia. Some of the effective antipsychotic treatments may have medication related adverse drug reactions appear in more than two-thirds of the patients [21, 22, 23], indicating the continuous need to search for prolactin-sparing solutions.

Furthermore, we are now aware that synthesis and secretion of prolactin is not restricted to the anterior lobe of the pituitary gland, but other organs and individual cells can also produce it. Indeed, the multiple roles and sources of prolactin had led Bern and Nicoll (*1968),* to suggest renaming it to "omnipotin" or "versatilin" [24]. This book provides the headlines to follow a course of cumulated knowledge on prolactin research during the last two-three decades and it may also help us understand some of the concerns that we face today.

#### **György M. Nagy** and **Dr Bela Ernest Toth**

Preface XI

[4] Freeman ME, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function, and

[5] MacLeod RM. Regulation of prolactin secretion. In: Martini L, Ganong WF, eds. Frontiers in Neuroendocrinology. New York: Raven Press; 1976. p. 169-94. [6] McCormick SD, Bradshaw D. Hormonal control of salt and water balance in

[7] Berczi I. The role of the growth and lactogenic hormone family in immune

[8] Dorshkind K, Horseman ND. Anterior pituitary hormones, stress, and immune

[9] Shelly S, Boaz M, Orbach H. Prolactin and autoimmunity. Autoimmun Rev. 2012 May;11(6-7):A465-70. doi: 10.1016/j.autrev.2011.11.009. Epub 2011 Dec 2. Review.

[10] Jara LJ, Medina G, Saavedra MA, Vera-Lastra O, Navarro C. Prolactin and autoimmunity. Clin Rev Allergy Immunol. 2011 Feb;40(1):50-9. doi:

[11] Orbach H, Shoenfeld Y. Hyperprolactinemia and autoimmune diseases. Autoimmun Rev. 2007 Sep;6(8):537-42. Epub 2006 Dec 1. Review. PubMed PMID:

[12] Zen M, Ghirardello A, Iaccarino L, Tonon M, Campana C, Arienti S et al. Hormones, immune response, and pregnancy in healthy women and SLE

[13] Kruger TH, Hartmann U, Schedlowski M. Prolactinergic and dopaminergic mechanisms underlying sexual arousal and orgasm in humans. World J Urol.2005;

[14] Simon JA. Low sexual desire--is it all in her head? Pathophysiology, diagnosis, and treatment of hypoactive sexual desire disorder. Postgrad Med. 2010

[15] Corona G, Ricca V, Bandini E, Mannucci E, Lotti F, Boddi V, Rastrelli G, Sforza A, Faravelli C, Forti G, Maggi M. Selective serotonin reuptake inhibitor-induced sexual dysfunction. J Sex Med. 2009 May;6(5):1259-69. doi: 10.1111/j.1743-

[16] Gettler LT, McDade TW, Feranil AB, Kuzawa CW. Prolactin, fatherhood, and reproductive behavior in human males. Am J Phys Anthropol. 2012 Jul;148(3):362-

[18] Gregg C. Pregnancy, prolactin and white matter regeneration. J Neurol Sci.2009;

[19] Orita S, Yoshinobu J, Orita Y, Tsujigiwa H, Kakiuchi M, Nagatsuka H, Nomiya S, Nagai N, Nishizaki K. Prolactin may stimulate proliferation in the olfactory epithelium of the female mouse. Am J Rhinol Allergy. 2009 Mar-Apr;23(2):135-8.

70. doi: 10.1002/ajpa.22058. Epub 2012 May 11. PubMed PMID: 22576125. [17] Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW et al. White matter plasticity and enhanced remyelination in the maternal CNS. J Neurosci.2007; 27:

10.1007/s12016-009-8185-3. Review. PubMed PMID: 19911311.

regulation of secretion. Physiol Rev.2000; 80: 1523-631.

vertebrates. Gen Comp Endocrinol.2006; 147: 3-8.

system homeostasis. Bioessays.2001; 23: 288-94.

patients. Swiss Med Wkly.2010; 140: 187-201.

6109.2009.01248.x. PubMed PMID: 19473282.

PubMed PMID: 22155203.

17854745.

23: 130-138.

1812-23.

285: 22-27.

doi: 10.2500/ajra.2009.23.3282.

Nov;122(6):128-36.

function. Neuroimmunomodulation.1994; 1: 201-16.

#### **References**


[4] Freeman ME, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function, and regulation of secretion. Physiol Rev.2000; 80: 1523-631.

X Preface

and women[15].

levels [16].

with increased prolactin levels [14]. A chronic hyperprolactinemia is clinically associated with hypogonadotropic hypogonadism and sexual dysfunction as well, while treatment of hyperprolactinemia restores normal sexual function both in men

Moreover, prolactin levels and our behavior are potentially also connected. Prolactin is higher during periods of nursing in some species, but also in human during "maternal" as well as "paternal" behavior: fathers of infants have elevated prolactin

Prolactin stimulates proliferation of oligodendrocyte precursor cells (they are cells that differentiate into oligodendrocytes, and they are responsible for the formation of myelin sheet of axons in the central nervous system (CNS)[17,18]. Interestingly, high

Prolactin can also be found in amniotic fluid and contributes to surfactant synthesis of

Since pituitary prolactin is under a close and mainly inhibitory control of hypothalamic dopaminergic system, it is predictable that drugs attenuating pathological neurotransmitter levels (like in schizophrenia, mood disturbances, etc) may have potential side effect resulting in clinical signs associated with or caused by hyperprolactinemia. Some of the effective antipsychotic treatments may have medication related adverse drug reactions appear in more than two-thirds of the patients [21, 22, 23],

Furthermore, we are now aware that synthesis and secretion of prolactin is not restricted to the anterior lobe of the pituitary gland, but other organs and individual cells can also produce it. Indeed, the multiple roles and sources of prolactin had led Bern and Nicoll (*1968),* to suggest renaming it to "omnipotin" or "versatilin" [24]. This book provides the headlines to follow a course of cumulated knowledge on prolactin research during the last two-three decades and it may also help us understand some of

[1] Riddle O, Bates RW, Dykshorn SW *(*1933*)* The preparation, identification and assay of prolactin—a hormone of anterior pituitary. *Am J Physiol* 105*:*191*–*216. [2] MacLeod RM. Influence of norepinephrine and catecholamine-depleting agents on the synthesis and release of prolactin and growth hormone. Endocrinology.

[3] Neill JD, Nagy GM. Prolactin secretion and its control. In: Knobil E, Neill J.D., eds.

Physiology of Reproduction. New York: Raven Press; 1994. p. 1833-60.

**György M. Nagy** and **Dr Bela Ernest Toth** 

prolactin levels stimulate the proliferation of olfactory epithelium[19].

indicating the continuous need to search for prolactin-sparing solutions.

fetal lungs at the end of pregnancy[20].

the concerns that we face today.

1969; 85: 916-23.

**References**

	- [20] Mendelson CR, Boggaram V. Hormonal control of the surfactant system in fetal lung. Annu Rev Physiol.1991; 53: 415-40.
	- [21] Carroll RW, Christodoulou P, Baynes KC, Kahn DA. Hyperprolactinemia in a patient with a pituitary adenoma receiving antipsychotic drug therapy. J Psychiatr Pract. 2012 Mar;18(2):126-9.
	- [22] Gallego JA, Nielsen J, De Hert M, Kane JM, Correll CU. Safety and tolerability of antipsychotic polypharmacy. Expert Opin Drug Saf. 2012 Jul;11(4):527-42. doi: 10.1517/14740338.2012.683523. Epub 2012 May 8.
	- [23] Inder WJ, Castle D. Antipsychotic-induced hyperprolactinaemia. Aust N Z J Psychiatry. 2011 Oct;45(10):830-7. doi: 10.3109/00048674.2011.589044. Epub 2011 Jun 30. Review. PubMed PMID: 21714721.
	- [24] Bern HA, Nicoll CS. The comparative endocrinology of prolactin. Recent Prog Horm Res. 1968;24:681-720. Review.

XII Preface

[20] Mendelson CR, Boggaram V. Hormonal control of the surfactant system in fetal

[21] Carroll RW, Christodoulou P, Baynes KC, Kahn DA. Hyperprolactinemia in a patient with a pituitary adenoma receiving antipsychotic drug therapy. J Psychiatr

[22] Gallego JA, Nielsen J, De Hert M, Kane JM, Correll CU. Safety and tolerability of antipsychotic polypharmacy. Expert Opin Drug Saf. 2012 Jul;11(4):527-42. doi:

[23] Inder WJ, Castle D. Antipsychotic-induced hyperprolactinaemia. Aust N Z J Psychiatry. 2011 Oct;45(10):830-7. doi: 10.3109/00048674.2011.589044. Epub 2011

[24] Bern HA, Nicoll CS. The comparative endocrinology of prolactin. Recent Prog

lung. Annu Rev Physiol.1991; 53: 415-40.

10.1517/14740338.2012.683523. Epub 2012 May 8.

Jun 30. Review. PubMed PMID: 21714721.

Horm Res. 1968;24:681-720. Review.

Pract. 2012 Mar;18(2):126-9.

**Chapter 1** 

© 2013 Muralidhar and Lee, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

The first observation related to prolactin was made in 1928 (Stricker and Grueter, 1928). These French scientists injected a bovine pituitary extract into pseudopregnant rabbits and

and reproduction in any medium, provided the original work is properly cited.

**Prolactin and Angiogenesis: Biological** 

Prolactin (PRL) was discovered in 1928. It is found in all vertebrates including humans. The name 'prolactin' is derived from its established role, in female mammals, in mammopoiesis. That raised the first mystery regarding its role in the human male and in non-mammalian vertebrates. More than 300 effects have been produced by injecting PRL into animals of all phylogenic groups. That raised the second mystery i.e. absence of any reliable and relevant bio assay for PRL till today. Following the approaches of Reductionist Biology, prolactin has been purified and characterized from a number of vertebrate groups. That raised the third mystery i.e. extensive microheterogeneity in structure and its doubtful relevance to physiology. The mechanism of action of prolactin has been studied extensively and that gave rise to the fourth mystery as to why it does not follow the second messenger model in signaling pathways, as in the case of other membrane receptor acting hormones like epinephrine or Luteinizing hormone (LH) or FSH etc. Prolactin behaves more like a cytokine and growth factor than like a hormone! In spite of exhibiting multiple physiological effects on a variety of tissues like brain (behavior), gonadal and mammary tissues, accessory sex organs like ventral prostate, immune system of phagocytes and lymphocytes etc, no disease whose origin can be ascribed to mutations in PRL or PRL receptor genes has yet been discovered. That is the fifth mystery. There is no known clinical model of prolactin deficiency. Hyperprolactinemia due to tumors of pituitary lactotrophs is the only known pathological condition. Long term hyperprolactinemia can lead to amenorrhea in women,

**Implications of Microheterogeneity** 

Kambadur Muralidhar and Jaeok Lee

loss of libido in men and infertility in both.

**2. Relevant biochemistry and biology of prolactin** 

http://dx.doi.org/10.5772/54318

**1. Introduction** 

Additional information is available at the end of the chapter

**Chapter 1** 
