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Physiol. Rev. 80: 1523-1631, 2000;
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Physiological Reviews, Vol. 80, No. 4, October 2000, pp. 1523-1631
Copyright ©2000 by the American Physiological Society

Prolactin: Structure, Function, and Regulation of Secretion

Marc E. Freeman, Béla Kanyicska, Anna Lerant, and György Nagy*

Department of Biological Science, Florida State University, Tallahassee, Florida; Department of Anatomy, The University of Mississippi Medical Center, Jackson, Mississippi; and Neuroendocrine Research Laboratory, Department of Human Morphology, Semmelweis University School of Medicine, Budapest, Hungary

Freeman, Marc E., Béla Kanyicska, Anna Lerant, and György Nagy. Prolactin: Structure, Function, and Regulation of Secretion. Physiol. Rev. 80: 1523-1631, 2000.Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

* The sequence of authorship does not imply importance of contribution but is presented alphabetically.




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S. Gentili, M. J. Waters, and I. C. McMillen
Differential regulation of suppressor of cytokine signaling-3 in the liver and adipose tissue of the sheep fetus in late gestation
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R1044 - R1051.
[Abstract] [Full Text] [PDF]

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 Proc R Soc BHome page
A. A Carlson, M. B Manser, A. J Young, A. F Russell, N. R Jordan, A. S McNeilly, and T. Clutton-Brock
Cortisol levels are positively associated with pup-feeding rates in male meerkats
Proc R Soc B, March 7, 2006; 273(1586): 571 - 577.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
M. Egli, R. Bertram, N. Toporikova, M. T. Sellix, W. Blanco, and M. E. Freeman
Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin
Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E566 - E572.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
R. Bertram, M. Egli, N. Toporikova, and M. E. Freeman
A mathematical model for the mating-induced prolactin rhythm of female rats
Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E573 - E582.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. T. Anderson, J. L. Barclay, K. J. Fanning, D. H. L. Kusters, M. J. Waters, and J. D. Curlewis
Mechanisms Underlying the Diminished Sensitivity to Prolactin Negative Feedback during Lactation: Reduced STAT5 Signaling and Up-Regulation of Cytokine-Inducible SH2 Domain-Containing Protein (CIS) Expression in Tuberoinfundibular Dopaminergic Neurons
Endocrinology, March 1, 2006; 147(3): 1195 - 1202.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
K. Foitzik, K. Krause, F. Conrad, M. Nakamura, W. Funk, and R. Paus
Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression
Am. J. Pathol., March 1, 2006; 168(3): 748 - 756.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. S. Tworoger, P. Sluss, and S. E. Hankinson
Association between Plasma Prolactin Concentrations and Risk of Breast Cancer among Predominately Premenopausal Women
Cancer Res., February 15, 2006; 66(4): 2476 - 2482.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
C. V. V. Helena, M. de Oliveira Poletini, G. L. Sanvitto, S. Hayashi, C. R. Franci, and J. A. Anselmo-Franci
Changes in {alpha}-estradiol receptor and progesterone receptor expression in the locus coeruleus and preoptic area throughout the rat estrous cycle
J. Endocrinol., February 1, 2006; 188(2): 155 - 165.
[Abstract] [Full Text] [PDF]

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 Sci SignalHome page
R. Bertram, J. Tabak, N. Toporikova, and M. E. Freeman
Endothelin Action on Pituitary Lactotrophs: One Receptor, Many GTP-Binding Proteins
Sci. Signal., January 24, 2006; 2006(319): pe4 - pe4.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
F. Y. Ma, G. M. Anderson, T. D. Gunn, V. Goffin, D. R. Grattan, and S. J. Bunn
Prolactin Specifically Activates Signal Transducer and Activator of Transcription 5b in Neuroendocrine Dopaminergic Neurons
Endocrinology, December 1, 2005; 146(12): 5112 - 5119.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
B. Rubi, S. Ljubicic, S. Pournourmohammadi, S. Carobbio, M. Armanet, C. Bartley, and P. Maechler
Dopamine D2-like Receptors Are Expressed in Pancreatic Beta Cells and Mediate Inhibition of Insulin Secretion
J. Biol. Chem., November 4, 2005; 280(44): 36824 - 36832.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
F. Obal Jr, F. Garcia-Garcia, B. Kacsoh, P. Taishi, S. Bohnet, N. D. Horseman, and J. M. Krueger
Rapid Eye Movement Sleep Is Reduced in Prolactin-Deficient Mice
J. Neurosci., November 2, 2005; 25(44): 10282 - 10289.
[Abstract] [Full Text] [PDF]

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 Exp PhysiolHome page
D. Low, A. Purvis, T. Reilly, and N. T. Cable
The prolactin responses to active and passive heating in man
Exp Physiol, November 1, 2005; 90(6): 909 - 917.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J.-C. Lu, T. M. Piazza, and L. A. Schuler
Proteasomes Mediate Prolactin-induced Receptor Down-regulation and Fragment Generation in Breast Cancer Cells
J. Biol. Chem., October 7, 2005; 280(40): 33909 - 33916.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
N. Wettschureck and S. Offermanns
Mammalian G Proteins and Their Cell Type Specific Functions
Physiol Rev, October 1, 2005; 85(4): 1159 - 1204.
[Abstract] [Full Text] [PDF]

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 ReproductionHome page
S. B Rulli and I. Huhtaniemi
What have gonadotrophin overexpressing transgenic mice taught us about gonadal function?
Reproduction, September 1, 2005; 130(3): 283 - 291.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. A. Andric, D. Zivadinovic, A. E. Gonzalez-Iglesias, A. Lachowicz, M. Tomic, and S. S. Stojilkovic
Endothelin-induced, Long Lasting, and Ca2+ Influx-independent Blockade of Intrinsic Secretion in Pituitary Cells by Gz Subunits
J. Biol. Chem., July 22, 2005; 280(29): 26896 - 26903.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Cristina, G. Diaz-Torga, A. Baldi, A. Gongora, M. Rubinstein, M. J. Low, and D. Becu-Villalobos
Increased Pituitary Vascular Endothelial Growth Factor-A in Dopaminergic D2 Receptor Knockout Female Mice
Endocrinology, July 1, 2005; 146(7): 2952 - 2962.
[Abstract] [Full Text] [PDF]

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 J Mol EndocrinolHome page
M Tanaka, M Suzuki, T Kawana, M Segawa, M Yoshikawa, M Mori, M Kobayashi, N Nakai, and T R Saito
Differential effects of sex steroid hormones on the expression of multiple first exons including a novel first exon of prolactin receptor gene in the rat liver
J. Mol. Endocrinol., June 1, 2005; 34(3): 667 - 673.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
G. M. Leclerc and F. R. Boockfor
Pulses of Prolactin Promoter Activity Depend on a Noncanonical E-Box that Can Bind the Circadian Proteins CLOCK and BMAL1
Endocrinology, June 1, 2005; 146(6): 2782 - 2790.
[Abstract] [Full Text] [PDF]

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 Eur J EndocrinolHome page
A.-K. Fjeldheim, P. I. Hovring, O.-P. Loseth, P. W. Johansen, J. C Glover, V. Matre, O. K. Olstad, S. Reppe, J. O Gordeladze, S I. Walaas, et al.
Thyrotrophin-releasing hormone receptor 1 and prothyrotrophin-releasing hormone mRNA expression in the central nervous system are regulated by suckling in lactating rats
Eur. J. Endocrinol., May 1, 2005; 152(5): 791 - 803.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
V. Goffin, S. Bernichtein, P. Touraine, and P. A. Kelly
Development and Potential Clinical Uses of Human Prolactin Receptor Antagonists
Endocr. Rev., May 1, 2005; 26(3): 400 - 422.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. Hattori, K. Ikekubo, Y. Nakaya, K. Kitagawa, and C. Inagaki
Immunoglobulin G Subclasses and Prolactin (PRL) Isoforms in Macroprolactinemia Due to Anti-PRL Autoantibodies
J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3036 - 3044.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
T. Matsutani, T. S. A. Samy, L. W. Rue III, K. I. Bland, and I. H. Chaudry
Transgenic prolactin-/- mice: effect of trauma-hemorrhage on splenocyte functions
Am J Physiol Cell Physiol, May 1, 2005; 288(5): C1109 - C1116.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
C Suarez, J Vela, I Garcia-Tornadu, and D Becu-Villalobos
Dehydroepiandrosterone (DHEA) modulates GHRH, somatostatin and angiotensin II action at the pituitary level
J. Endocrinol., April 1, 2005; 185(1): 165 - 172.
[Abstract] [Full Text] [PDF]

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 ReproductionHome page
J. M Russell, E Murphree, J Janik, and P Callahan
Effect of steroids and nitric oxide on pituitary hormone release in ovariectomized, peripubertal rats
Reproduction, April 1, 2005; 129(4): 497 - 504.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. A. Mennella, M. Y. Pepino, and K. L. Teff
Acute Alcohol Consumption Disrupts the Hormonal Milieu of Lactating Women
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 1979 - 1985.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
K. A. Felmet, M. W. Hall, R. S. B. Clark, R. Jaffe, and J. A. Carcillo
Prolonged Lymphopenia, Lymphoid Depletion, and Hypoprolactinemia in Children with Nosocomial Sepsis and Multiple Organ Failure
J. Immunol., March 15, 2005; 174(6): 3765 - 3772.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
N. Wettschureck, A. Moers, B. Wallenwein, A. F. Parlow, C. Maser-Gluth, and S. Offermanns
Loss of Gq/11 Family G Proteins in the Nervous System Causes Pituitary Somatotroph Hypoplasia and Dwarfism in Mice
Mol. Cell. Biol., March 1, 2005; 25(5): 1942 - 1948.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
J. H Hollis, S. L Lightman, and C. A Lowry
Lipopolysaccharide has selective actions on sub-populations of catecholaminergic neurons involved in activation of the hypothalamic-pituitary-adrenal axis and inhibition of prolactin secretion
J. Endocrinol., February 1, 2005; 184(2): 393 - 406.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
C M Gomes, C Raineki, P R. de Paula, G S Severino, C V V Helena, J A Anselmo-Franci, C R Franci, G L Sanvitto, and A B Lucion
Neonatal handling and reproductive function in female rats
J. Endocrinol., February 1, 2005; 184(2): 435 - 445.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
N. N. Bulayeva, A. L. Wozniak, L. L. Lash, and C. S. Watson
Mechanisms of membrane estrogen receptor-{alpha}-mediated rapid stimulation of Ca2+ levels and prolactin release in a pituitary cell line
Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E388 - E397.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
F. Y. Ma, D. R. Grattan, V. Goffin, and S. J. Bunn
Prolactin-Regulated Tyrosine Hydroxylase Activity and Messenger Ribonucleic Acid Expression in Mediobasal Hypothalamic Cultures: The Differential Role of Specific Protein Kinases
Endocrinology, January 1, 2005; 146(1): 93 - 102.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. J. Phelps
Postnatal Regression of Hypothalamic Dopaminergic Neurons in Prolactin-Deficient Snell Dwarf Mice
Endocrinology, December 1, 2004; 145(12): 5656 - 5664.
[Abstract] [Full Text] [PDF]


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