Biological Sciences
Prolactin
Prolactin is a hormone produced by the pituitary gland that plays a key role in lactation and breast development in females. It also has various effects on the immune system, metabolism, and behavior. Prolactin levels are regulated by multiple factors, including stress, sleep, and dopamine. Imbalances in prolactin levels can lead to reproductive and metabolic disorders.
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11 Key excerpts on "Prolactin"
eBook - ePubYen & Jaffe's Reproductive Endocrinology E-Book
Yen & Jaffe's Reproductive Endocrinology E-Book
- Antonio R. Gargiulo, Jerome F. Strauss, Robert L. Barbieri, Jerome F. Strauss, Robert L. Barbieri(Authors)
- 2017(Publication Date)
- Elsevier(Publisher)
Chapter 3Prolactin and Its Role in Human Reproduction
Nicholas A. Tritos Anne KlibanskiProlactin (PRL) is a single chain (23-kDa) polypeptide hormone that is secreted by anterior pituitary lactotroph cells.1 Several lines of evidence indicate that PRL has an essential role in reproduction and lactation.2 In addition, animal data have supported a role for PRL in a variety of metabolic processes.2 However, such PRL actions have not been unequivocally confirmed in humans. The present chapter reviews PRL physiology, followed by a discussion of the role of PRL in pathologic states, including hyperProlactinemia and PRL deficiency. Data on the epidemiology, pathology, clinical evaluation, and management of PRL-secreting pituitary adenomas (Prolactinomas) are then reviewed, including data relevant to Prolactinomas in the setting of preconception and pregnancy.Lactotroph Development
◆ Lactotroph cells develop under carefully orchestrated control by several transcription factors. ◆ Lactotroph hyperplasia is physiologic during pregnancy and is reversible postpartum.Pituitary lactotrophs are relatively abundant in the human anterior pituitary gland, accounting for up to 25% of cells in individuals of both genders.3 During embryogenesis, the pituitary gland develops from ectodermal primordial cells, destined to form the anterior and intermediate lobe and neuroectodermal tissue arising from the floor of the diencephalon, which ultimately forms the posterior lobe. During development, inductive interactions and a host of transcription factors are critical in the formation of the pituitary and differentiation into mature functioning cells.4 - 6 Transcription factors that have been implicated in pituitary ontogenesis include SIX3, HESX1, LHX3, LHX4, SOX2, SOX3, PITX2, OTX2, BMP2, BMP4, and GLI2.4 - 6
eBook - PDFClinical Neuroendocrinology
An Introduction
- Michael Wilkinson, S. Ali Imran(Authors)
- 2019(Publication Date)
- Cambridge University Press(Publisher)
Chapter 7 Hypothalamic Regulation of Prolactin Secretion Prolactin (PRL) plays an essential role in inducing breast enlargement during pregnancy and in stimu- lating lactation postpartum. PRL is produced and secreted from anterior pituitary gland lactotrophs in response to the suckling stimulus. Lactotrophs com- prise approximately 9% of hormone-secreting ante- rior pituitary cells in males, but this figure may reach 25% in multiparous women (Heaney and Melmed, 2004). This chapter will outline the mechanisms by which PRL levels are regulated under normal physio- logical conditions, and in those states of pathological PRL secretion, such as hyperProlactinemia. Human PRL, a 23 kDa protein, is encoded by a single gene, PRL, located on chromosome 6. However, several variants of the PRL protein are also identifi- able in blood samples. One of these, macroProlactin (macroPRL), is of high molecular mass (>100 kDa) and is detectable by PRL radiometric assays. Although it has no known biological function, and is therefore assumed to be clinically irrelevant, its presence in sera from patients can give misleadingly high values of PRL. These may lead to misdiagnosis and misman- agement of hyperProlactinemic patients (Fahie- Wilson and Smith, 2013; Samson et al., 2015; see Section 7.19). PRL is also expressed in a variety of human extra- pituitary tissues such as decidua, ovary, prostate, immune system cells and adipose tissue (Marano and Ben-Jonathan, 2014; Harvey et al., 2015). PRL is known to exert autocrine effects in human mammary epithelial cells, inducing terminal differentiation dur- ing late pregnancy, but a physiological role for locally produced PRL in other tissues is currently unknown (Bernard et al., 2015). Clinical implications: Presence of high serum PRL without the associated clinical symptoms of hyper- Prolactinemia should alert the clinician about the possibility of macroProlactinemia.
eBook - PDF- M. Y. Kalimi, J. R. Hubbard(Authors)
- 2019(Publication Date)
- De Gruyter(Publisher)
The purpose of this chapter is to provide an overview and critical analysis of the past, current, and possibly future concepts regarding the mechanism of action of Prolactin. In this review we attempt to cover this vast field in three parts. In the first part we review the physiological action of Prolactin and its relationship to other hormones. The second part deals with the Prolactin receptor. Here we discuss Prolactin radioreceptor methodology, the distribution and regulation of Prolactin receptivity in mammalian target tissues, and some recent studies pertaining to the role of membrane phenomena in receptor regulation. The third part covers the concepts of Prolactin signal transduction. In this section we discuss the available information and prevailing views regarding intracellular mediators for Prolactin as well as the entry of Prolactin into its target cells. How Prolactin internalization relates to signal transduction is also be discussed. Finally, some recent work concerning the target organ proteolytic processing is reviewed as well as its possible relationship to internalization and signal transduction. Physiological Actions of Prolactin Prolactin as a lactogenic hormone The anterior pituitary hormone Prolactin (PRL) has a wide variety of effects in many different vertebrate species. Although Bern and Nicoll (1,2) and deVlaming (3) have catalogued more than one hundred reported actions of PRL, the function for which the hormone received its most widely used name derives from its effect on the mammary gland. The maturation of the mammary gland and the production of milk require a complex interaction of many hormones other than PRL. 65 As reviewed by Lyons et al. (4) and Topper (5), and more recently by Vonderhaar and Bhattacharjee(6), all of the anterior pituitary hormones participate either directly or indirectly in the development of the mammary gland and lactogenesis.
- Kenneth Fotherby(Author)
- 2019(Publication Date)
- De Gruyter(Publisher)
SYNTHESIS, RELEASE, AND BIOLOGICAL ACTIONS OF HUMAN Prolactin C. Ferrari Second Department of Medicine, Fatebenefratelli Hospital, 23 Corso di Porta Nuova, 20121 Milano, Italy Introduction Prolactin (PRL) was discovered by Strieker and Grueter as a lactogenic substance present in mammalian pituitary extracts about 50 years ago. However, due to the small amount of PRL present in the human pituitary and to the strong intrinsic lactogenic effect of human growth hormone (GH), it was not un-til 1970 that the existence of PRL as a separate substance in human pituitary (1) and plasma (2) was finally demonstrated. PRL is phylogenetically the oldest polypeptide hormone secre-ted by the pituitary gland and it subserves a great number of different functions among the vertebrates, many of which are important only to certain species or groups (3). Although cli-nical studies have so far dealt mainly with the actions of hu-man PRL on lactation and reproductive function, there is proba-bly much more to learn on the role of this hormone in normal and pathological physiology. Synthesis of Prolactin in Human Tissues Human PRL is synthesized in the lactotrophic cells of the ante-rior pituitary gland, in the decidual cells of the placenta, and rarely by some non-endocrine tumours. The entire linear amino acid sequence of human pituitary PRL isolated from frozen glands has been reported (4). The number of amino acid residues, 198, is identical to that of porcine, ovine, and rat PRL; how-Hormones in Normal and Abnormal Human Tissues © Walter de Gruyter • Berlin New York 1981 282 ever, sequence identity is 77, 73 and 60%, respectively. Ninety-nine residues are identical in sequence position in all four species. The structure of human PRL bears very little similarity with human growth hormone, as only 32 residues are in identical position in the two hormones. The pituitary content of PRL is very small, between 100 and 500 ug per gland.
eBook - PDFHormones and their Actions, Part 2
Specific action of protein hormones
- B.A. Cooke, R.J.B. King, H.J. Van Der Molen(Authors)
- 1988(Publication Date)
- Elsevier Science(Publisher)
However, it is also possible that internalization of the hormone-re- ceptor complex plays an important part in mediating the actions of the hormone. The interaction of factors regulating levels of Prolactin receptors [26,56] in a va- riety of tissues is complex and not fully understood. The topic will not be consid- ered in detail here. The actions of Prolactin itself on the process will be discussed briefly, however. In the short term, Prolactin often leads to down-regulation of its own receptors, presumably as a consequence of internalization following binding of 304 hormone to receptor. In the longer term, however, the hormone usually leads to up-regulation of its receptors, as has been demonstrated in a range of tissues [26,56,62]. GH, too, may lead to an increase in the level of Prolactin receptors in some tissues [63]. 4. Biochemical mode of action of Prolactin on the mammary gland The main actions of Prolactin in female mammals involve stimulation of mammary growth and function, and it is in this area that the bulk of work on the biochemical mode of action of the hormone has been concentrated. 4.1. Actions on mammary gland differentiation and development The development of the mammary gland both during puberty and pregnancy is un- der the control of a number of hormones [15,16,6466], but these differ according to the species. During puberty oestrogens, and possibly progesterone, play a cen- tral part in the development of the gland, and insulin, GH and/or Prolactin (pos- sibly via the mediation of somatomedins or related polypeptides) may also be nec- essary at this stage. Development during puberty mainly involves growth of the ductal system of the gland, relatively few secretory alveoli being present prior to the first pregnancy. During pregnancy some additional branching of the ductal sys- tem occurs, together with formation of the secretory alveoli which actually produce the milk components.
- George H. Gass, Harold M. Kaplan(Authors)
- 2020(Publication Date)
- CRC Press(Publisher)
Table 2 ).ACTIONS OF Prolactin
The effects of Prolactin in mammals are exerted primarily on the organs of reproduction. Prolactin is also an important factor in the regulation of the immune system,99 pancreatic development,100 and metabolism.With regard to reproduction Prolactin stimulates the secretion of milk during lactation and promotes the growth of the mammary glands during pregnancy.101 , 102 , 103Prolactin can induce lactogenesis in ovariectomized, adrenalectomized, and hypophysectomized rats and mice when it is given in combination with an adrenal corticosteriod.104 , 105Prolactin induces polarity in mammary gland cells106 and the appearance of golgi vesicles which contain casein. In vitro Prolactin can induce casein synthesis,107 , 108 , 109α-lactalbumin,110 , 111 lactose, and milk fat synthesis.112 , 113In rodents, Prolactin activates the corpus luteum and acts as part of a luteotropic complex with LH to maintain corpus luteum function.114 In other species Prolactin is not a factor in the regulation of the corpus luteum, but Prolactin may be trophic to the regulation of granulosa cell function in the human ovary.115 , 116 Prolactin also acts on the testes, stimulating gonadotropin binding and increasing testosterone production.117 , 118 Prolactin acts on the prostate gland and increases prostatic secretions. Prolactin receptors have been demonstrated in the prostate gland.119 Prolactin can stimulate growth and differentiation of prostate cells in vitro.120At high concentrations, Prolactin is antigonadotropic. Prolactin has a direct inhibitory effect on the hypothalamus and prevents gonadotropin secretion.117 , 121 Studies in rodents show that Prolactin can prevent the release of gonadotropins in response to gonadectomy.122 , 123 More recently, it has been shown that Prolactin can reduce LHRH secretion from cultured LHRH cells in vitro.44 These results suggest that hyperProlactinemia can prevent hypothalamic LHRH release. Prolactin also has direct antigonadal effects. It can be luteolytic in the rat. At high levels, Prolactin reduces 20α-hydroxysteroid dehydrogenase activity in the ovary.124 , 125 These antigonadotropic effects of Prolactin occur both during lactation and in disorders of Prolactin secretion.53
eBook - ePub- Paul V. Malven(Author)
- 2019(Publication Date)
- CRC Press(Publisher)
Figure 7-1 ). This glycosylation occurs at residue 31 (asparagine) in PRL from sheep, pigs, mice, and humans, but not from cattle which have an aspartate residue at position 31 (Strickland and Pierce, 1985). Within the pars anterior tissue, only a fraction of the total PRL is glycosylated (Sinha, 1992), and this proportion varies greatly among species (e.g., 8–50 %). Glycosylated PRL also occurs in blood plasma, but its biological significance is not fully understood. The glycosylated molecules have bioactivity, but it is usually less than the major nonglycosylated form (Sinha, 1992). In addition to the major 23,000 Da form of PRL, there are several other variants of the molecule that also possess bioactivity, but additional research is needed to understand the physiological relevance of the PRL variants.Biological Actions of Prolactin
Adenohypophysial PRL is a hormone that occurs across all vertebrate species, and it is involved in many different functions. Unlike other hormones of the adenohypophysis, PRL was apparently not committed early in evolution to a particular target organ or biological process. Therefore, the biological actions of PRL are diversified and highly adaptive in nature. A major function of PRL in female mammals is stimulation of milk production by the mammary gland for support of neonatal offspring. This nurturing role for PRL first appears in pigeons where the PRL-stimulated crop sac produces the functional equivalent of mammalian milk for the offspring. Other actions of PRL in vertebrates modulate the processes of reproduction, osmoregulation, growth/metabolism, as well as maternal and migratory behaviors.Mammotrophic Actions of PRL. After mammary tissue has been suitably prepared by the maternal hormones of pregnancy, stimulation by PRL is required in all mammals to initiate lactogenesis (defined as copious secretion of milk). This mammary requirement for PRL has been demonstrated in vitro as well as in vivo using hypophysectomized females or those in which the secretion of PRL has been inhibited by pharmacological agents. In both types of in vivo
eBook - PDF- Choh Hao Li(Author)
- 2012(Publication Date)
- Academic Press(Publisher)
HORMONAL PROTEINS AND PEPTIDES, VOL. VIII 2 The Role of Prolactin in Normal Mammary Gland Growth and Function J O E L J. ELIAS I. Introduction 37 II. Hormonal Requirements 40 A. Lobuloalveolar Growth in Vivo 40 B. Lactogenesis in Vivo 42 C. Lactogenesis in Organ Culture 46 III. Effect of Prolactin on Lactogenesis in Organ Culture 49 IV. Mechanism of Action of Prolactin 60 A. Membrane Receptors 60 B. Intracellular Mediators 62 V. Effect of Hormones on Growth in Organ Culture 66 VI. Concluding Remarks 70 References 71 I. Introduction The discovery by Strieker and Grueter (1928, 1929) that an extract of the anterior pituitary could stimulate milk secretion in rabbits ushered in a period of intensive research on the role of the pituitary in mammary gland growth and secretion. It soon became apparent that the hormonal regula- tion of the mammary gland was exceedingly complex and involved a number of endocrine glands. The mammary gland is unique in the sense that it exists in the young adult female mammal in a relatively rudimentary state of development. Before it achieves its fully functional state of milk secretion for the nourishment of the newborn, it first undergoes a period of extensive growth resulting in an enormous increase in numbers of the structural units, the alveoli, mainly responsible for milk secretion. These Copyright © 1980 by Academic Press, Inc. All rights of reproduction in any form reserved. ISBN 0-12-447208-7 38 JOEL J. ELIAS alveoli are organized into groups or lobules; hence, this phase of devel- opment is referred to as lobuloalveolar growth and it normally takes place in pregnancy. After weaning of the young, practically all the alveoli that had developed during pregnancy undergo degeneration and the gland re- turns to its rudimentary state in the nonpregnant animal.
eBook - PDF- Luciano Martini(Author)
- 2012(Publication Date)
- Academic Press(Publisher)
Chapter 14 Prolactin: Clinical Physiology and the Significance and Management of Η^βφΓθΙαοαηβϋύα M. O. Thorner I. Introduction 320 II. Secretory Patterns 320 A. Fetal and Neonatal Life 320 B. Puberty 320 C. Pregnancy 321 D. Old Age 322 E. 24-Hour Secretory Pattern 322 F. Menstrual Cycle 323 G. Pulsatility of Prolactin Secretion 324 H. Reflex Prolactin Secretion 325 III. Normal Control of Prolactin Secretion 326 A. Introduction 326 B. The Nature of Prolactin Release-Inhibiting Factor (PIF) 327 C. Thyrotropin-Releasing Hormone (TRH) as a Prolactin-Re-leasing Factor 329 D. Serotonin and Prolactin Secretion 330 IV. Physiological Role of Prolactin 330 A. Introduction 330 B. Lactation 331 C. Fluid and Electrolyte Balance 332 D. Prolactin and Adrenocortical Function 334 E. Prolactin and Growth 334 V. Dynamic Tests for Prolactin Secretion 334 Basal Serum Prolactin Level 336 VI. Disorders of Prolactin Secretion 336 A. Deficiency of Prolactin 336 B. HyperProlactinemia 337 C. HyperProlactinemia in the Male 342 319 M. O. Thorner D. HyperProlactinemia and Pituitary Tumors 343 E. Management of Patients with HyperProlactinemia 345 VII. Mechanisms of Hypogonadism in HyperProlactinemia 352 VIE. Conclusions 355 References 355 I. INTRODUCTION Prolactin is unique among the anterior pituitary hormones in being predomi-nantly under inhibitory control of the hypothalamus. The hypothalamus is not necessary for the development of Prolactin-secreting cells in the anterior pituitary or for its secretion, as Prolactin secretion is normal in anencephalic fetuses (Aubert et al., 1975). Disorders of Prolactin are probably important for a wide variety of metabolic diseases, but only its roles in normal and abnormal lactation and their relationship with gonadal function have been established in man. II. SECRETORY PATTERNS A. Fetal and Neonatal Life Prolactin levels in the serum of fetuses before 25 weeks of gestation are slightly higher than in normal adults.
eBook - ePub- Vincent Geenen(Author)
- 2004(Publication Date)
- CRC Press(Publisher)
7 ]. We will briefly consider the nature and the sources of lactogenic hormones: their receptors, their biochemical and molecular effects in leukocytes, their in vivo and in vitro effects on the development of the immune system and on immune responses, their possible role in hemopoietic malignancies and in tumor immunology. Signaling through the PRL-R has been covered in detail in Chapter 2. We will critically review evidence that PRL is the oldest cytokine and, more important, that it is a hemapoietic growth and differentiation factor in mammals.II. Prolactin: A FAMILY OF MOLECULES
A. Pituitary Prolactin
PRL is the prototype of lactogenic hormones. In mammals, its main actions are related to the development of the mammary gland and milk production [1 ,2 ]. Several other hormones and growth factors are involved in these processes, but only agonists acting through the PRL receptor (PRL-R or lactogenic receptor) are called lactogens. In addition to PRL, the lactogenic hormones include GH (from primates only) and placental lactogens. There is only one gene for PRL in human, mouse, and rat, mapping close to the MHC in the human (on chromosome 6, 6p22.2–p21.3). In the mouse in particular, many PRL-related proteins (PLP) are coded for by related genes, but, having no lactogenic activity, they are not considered here [2 ]. One of these, the murine PRL-like protein PLP-E, is a true hemopoietic growth factor [12 ].PRL is the most abundant pituitary hormone in humans. It is a 4-helix-bundle polypeptide with a strong homology to GH and placental lactogen and a weak homology to other cytokines such as interleukin (IL)-6. The major form of PRL is 23 kDa PRL in the human, mouse, and rat. Posttranslational modifications yield a large array of PRL variants. PRL can undergo glycosylation, phosphorylation, dimerization (big PRL), or proteolytic cleavage. Some features of PRL are summarized in Table 1. The PRL variants differ in their specific activity. Immunoreactive forms with an apparent molecular weight of 45 kDa or more in reduced gels have been detected, but in most cases compelling evidence that they are indeed products of the PRL gene was missing. High molecular weight complexes containing PRL [“big-big PRL,” consisting of PRL multimers or PRL-immunoglobulin (PRL-Ig) complexes, possibly PRL-antiPRL complexes] are also found in normal and pathological sera. In some cases, the presence of a covalent linkage between PRL and Ig has been ascertained [13 –15 ]. Big-big PRL is active in vitro (Nb2 assay) but not in vivo (due to poor crossing of the endothelial barrier). A 16 kDa N-terminal proteolytic fragment of rat PRL does not bind the PRL-R but has biological (e.g., antiangiogenic) activity [16 ,17 ]. The 6 kDa C-terminal fragment has some residual lactogenic activity [18
eBook - PDFThe Hormones V1
Physiology, Chemistry and Applications
- Mohhamad Reza Kiani(Author)
- 2012(Publication Date)
- Academic Press(Publisher)
The secretion of Prolactin—which we may instance as one contributory factor to the total lactogenic effect—would probably be below maximal in most animals having interthreshold prolactational con-centrations of systemic estrogen, and in consequence galactopoiesis would be expected to follow any treatment which could raise the sys-temic Prolactin level. Such an interpretation lays special emphasis on the authors' opinion, already expressed, that lactogenesis and galacto-poiesis may be different aspects of the activity of the same pituitary hor-monal complex, whose components vary in their relative importance both in the changing phases of the lactation cycle and, we might expect, under the sometimes artificial conditions of experimental procedure. In the particular case we are considering, the possibility that the beneficial effect of the pituitary extracts may have been attributable to Prolactin— rather than glycotropin—clearly cannot be discounted by reference to the inability of Prolactin to give a galactopoietic effect in normally lactating cows. The influence of hormones, other than those of the ovary, upon Prolactin secretion has not yet received very extensive study,' but Turner and Meites (280) have reported that injections of desoxycorticosterone acetate given to guinea pigs failed to influence the pituitary content of X V I . HORMONAL CONTROL OF LACTATION 789 this hormone, while it was believed (176) that the definite reduction which followed adrenalectomy in rats was probably due to secondary effects attending the operation, such as the cessation of estrous cycles, or a reduced food intake. Since, however, the sudden rise of Prolactin levels at parturition was demonstrated for rats adrenalectomized during the last week of pregnancy, it was further concluded that failure of lacta-tion following this operation was not primarily a matter of Prolactin deficiency.
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