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Endocrine Reviews, doi:10.1210/edrv-17-6-639
Endocrine Reviews 17 (6): 639-669
Copyright © 1996 by The Endocrine Society
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Extrapituitary Prolactin: Distribution, Regulation, Functions, and Clinical Aspects*

NIRA BEN-JONATHAN, JOHN L. MERSHON{dagger}, DONALD L. ALLEN and ROSEMARY W. STEINMETZ{ddagger}

Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine Cincinnati, Ohio 45267

Correspondence: Address reprint requests to: Nira Ben-Jonathan, Ph.D., Department of Cell Biology, University of Cincinnati, 231 Bethesda Avenue, Cincinnati, Ohio 45267-0521.

Abstract

I. Introduction: PRL affects more physiological processes than all other pituitary hormones combined. Among these are the regulation of mammary gland development, initiation and maintenance of lactation, immune modulation, osmoregulation, and behavioral modification. At the cellular level, PRL exerts mitogenic, morphogenic, or secretory activities. This raises the question as to the mechanism by which a single hormone can modulate so many seemingly unrelated functions. This review addresses the concept of the dual function of PRL, as a circulating hormone and a cytokine. The diversity of PRL actions is derived from three components: structural polymorphism, local production and processing, and divergent intracellular signaling pathways and target genes. PRL can be easily classified as a cytokine based on its shared properties with hematopoietic growth factors. These include comparable structural motifs, multiple sites of synthesis, ubiquitous receptor distribution, homologous receptor structure, and similar signal transduction pathways.

A seminal report by Nagy and Berczi (1) drew attention to extrapituitary PRL. They reported that hypophysectomized female rats had 10–20% lactogenic activity in their serum as compared with controls. Within 2 months, the lactogenic activity gradually increased to 50% of controls.

Footnotes

* This work was supported by National Science Foundation (Grant IBN94-09133), National Institutes of Health (Grant NS-13243), US Army (Grant DAMD17-94-J-4452) and Center for Environmental Genetics (Grant P30 ES06096).

{dagger} Current address: Department of Obstetrics and Gynecology, University of Cincinnati School of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267.

{ddagger} Current address: Department of Obstetrics and Gynecology, Indiana University School of Medicine, 1001 West Walnut Street, MF 103, Indianapolis, Indiana 46202.




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 Ann Rheum DisHome page
A M Jacobi, W Rohde, H-D Volk, T Dorner, G-R Burmester, and F Hiepe
Prolactin enhances the in vitro production of IgG in peripheral blood mononuclear cells from patients with systemic lupus erythematosus but not from healthy controls
Ann Rheum Dis, March 1, 2001; 60(3): 242 - 247.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Ling, G. Hellgren, M. Gebre-Medhin, K. Dillner, H. Wennbo, B. Carlsson, and H. Billig
Prolactin (PRL) Receptor Gene Expression in Mouse Adipose Tissue: Increases during Lactation and in PRL-Transgenic Mice
Endocrinology, October 1, 2000; 141(10): 3564 - 3572.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
F. Xu, W. Xia, R. Z. Luo, H. Peng, S. Zhao, J. Dai, Y. Long, L. Zou, W. Le, J. Liu, et al.
The Human ARHI Tumor Suppressor Gene Inhibits Lactation and Growth in Transgenic Mice
Cancer Res., September 1, 2000; 60(17): 4913 - 4920.
[Abstract] [Full Text]

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 EndocrinologyHome page
N. Binart, C. Helloco, C. J. Ormandy, J. Barra, P. Clement-Lacroix, N. Baran, and P. A. Kelly
Rescue of Preimplantatory Egg Development and Embryo Implantation in Prolactin Receptor-Deficient Mice after Progesterone Administration
Endocrinology, July 1, 2000; 141(7): 2691 - 2697.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J. T. FASSETT, R. T. HAMILTON, and M. NILSEN-HAMILTON
Mrp4, A New Mitogen-Regulated Protein/Proliferin Gene; Unique in this Gene Family for its Expression in the Adult Mouse Tail and Ear
Endocrinology, May 1, 2000; 141(5): 1863 - 1871.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J. Reese, N. Binart, N. Brown, W.-g. Ma, B. C. Paria, S. K. Das, P. A. Kelly, and S. K. Dey
Implantation and Decidualization Defects in Prolactin Receptor (PRLR)-Deficient Mice Are Mediated by Ovarian But Not Uterine PRLR
Endocrinology, May 1, 2000; 141(5): 1872 - 1881.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. M. Corbacho, G. Nava, J. P. Eiserich, G. Noris, Y. Macotela, I. Struman, G. Martinez de la Escalera, B. A. Freeman, and C. Clapp
Proteolytic Cleavage Confers Nitric Oxide Synthase Inducing Activity upon Prolactin
J. Biol. Chem., April 28, 2000; 275(18): 13183 - 13186.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
I. Olazabal, J. Muñoz, S. Ogueta, E. Obregón, and J. P. García-Ruiz
Prolactin (PRL)-PRL Receptor System Increases Cell Proliferation Involving JNK (c-Jun Amino Terminal Kinase) and AP-1 Activation: Inhibition by Glucocorticoids
Mol. Endocrinol., April 1, 2000; 14(4): 564 - 575.
[Abstract] [Full Text]

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 J. Histochem. Cytochem.Home page
T. Iwasaka, S. Umemura, K. Kakimoto, H. Koizumi, and Y. R. Osamura
Expression of Prolactin mRNA in Rat Mammary Gland During Pregnancy and Lactation
J. Histochem. Cytochem., March 1, 2000; 48(3): 389 - 396.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
Expression of Prolactin-Releasing Peptide and Its Receptor Messenger Ribonucleic Acid in Normal Human Pituitary and Pituitary Adenomas
J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4652 - 4655.
[Abstract] [Full Text]

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 EndocrinologyHome page
O. Gualillo, F. Lago, M. García, C. Menéndez, R. Señarís, F. F. Casanueva, and C. Diéguez
Prolactin Stimulates Leptin Secretion by Rat White Adipose Tissue
Endocrinology, November 1, 1999; 140(11): 5149 - 5153.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
J. Frasor, C. A. Gaspar, K. M. Donnelly, G. Gibori, and A. T. Fazleabas
Expression of Prolactin and Its Receptor in the Baboon Uterus during the Menstrual Cycle and Pregnancy
J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3344 - 3350.
[Abstract] [Full Text]

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 EndocrinologyHome page
S. Khurana, K. Liby, A. R. Buckley, and N. Ben-Jonathan
Proteolysis of Human Prolactin: Resistance to Cathepsin D and Formation of a Nonangiostatic, C-Terminal 16K Fragment by Thrombin
Endocrinology, September 1, 1999; 140(9): 4127 - 4132.
[Abstract] [Full Text]

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 EndocrinologyHome page
N. A. Mitchner, C. Garlick, R. W. Steinmetz, and N. Ben-Jonathan
Differential Regulation and Action of Estrogen Receptors {alpha} and {beta} in GH3 Cells
Endocrinology, June 1, 1999; 140(6): 2651 - 2658.
[Abstract] [Full Text]

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 ChestHome page
B. Chernow
Variables Affecting Outcome in Critically Ill Patients
Chest, May 1, 1999; 115 (2009): 71S - 76S.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
I. Leav, F. B. Merk, K. F. Lee, M. Loda, M. Mandoki, J. E. McNeal, and S.-m. Ho
Prolactin Receptor Expression in the Developing Human Prostate and in Hyperplastic, Dysplastic, and Neoplastic Lesions
Am. J. Pathol., March 1, 1999; 154(3): 863 - 870.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. Clément-Lacroix, C. Ormandy, L. Lepescheux, P. Ammann, D. Damotte, V. Goffin, B. Bouchard, M. Amling, M. Gaillard-Kelly, N. Binart, et al.
Osteoblasts Are a New Target for Prolactin: Analysis of Bone Formation in Prolactin Receptor Knockout Mice
Endocrinology, January 1, 1999; 140(1): 96 - 105.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
N. Subramaniam, W. Cairns, and S. Okret
Glucocorticoids Repress Transcription from a Negative Glucocorticoid Response Element Recognized by Two Homeodomain-containing Proteins, Pbx and Oct-1
J. Biol. Chem., September 4, 1998; 273(36): 23567 - 23574.
[Abstract] [Full Text] [PDF]

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 LupusHome page
S E Walker, D Miller, D L Hill, and G R Komatireddy
Prolactin, a pituitary hormone that modifies immune responses: Proceedings of the Mini-symposium on Prolactin and SLE, held at the 5th International Conference on Systemic Lupus Erythematosus, Cancun, Mexico
Lupus, July 1, 1998; 7(6): 371 - 375.
[PDF]

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 Endocr. Rev.Home page
C. Bole-Feysot, V. Goffin, M. Edery, N. Binart, and P. A. Kelly
Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice
Endocr. Rev., June 1, 1998; 19(3): 225 - 268.
[Abstract] [Full Text]

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 EndocrinologyHome page
T.-J. Chen, C. B. Kuo, K. F. Tsai, J.-W. Liu, D.-Y. Chen, and A. M. Walker
Development of Recombinant Human Prolactin Receptor Antagonists by Molecular Mimicry of the Phosphorylated Hormone
Endocrinology, February 1, 1998; 139(2): 609 - 616.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. L. Jones, H. O. D. Critchley, J. Brooks, H. N. Jabbour, and A. S. McNeilly
Localization and Temporal Expression of Prolactin Receptor in Human Endometrium
J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 258 - 262.
[Abstract] [Full Text]

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 EndocrinologyHome page
C. Reynolds, K. T. Montone, C. M. Powell, J. E. Tomaszewski, and C. V. Clevenger
Expression of Prolactin and Its Receptor in Human Breast Carcinoma
Endocrinology, December 1, 1997; 138(12): 5555 - 5560.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
Y.-f. Wang, K. D. O’Neal, and L.-y. Yu-Lee
Multiple Prolactin (PRL) Receptor Cytoplasmic Residues and Stat1 Mediate PRL Signaling to the Interferon Regulatory Factor-1 Promoter
Mol. Endocrinol., August 1, 1997; 11(9): 1353 - 1364.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
Y. Cheng, I. Zhizhin, R. L. Perlman, and D. Mangoura
Prolactin-induced Cell Proliferation in PC12 Cells Depends on JNK but Not ERK Activation
J. Biol. Chem., July 21, 2000; 275(30): 23326 - 23332.
[Abstract] [Full Text] [PDF]


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