This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by SINHA, Y. N. Search for Related Content PubMed PubMed Citation Articles by SINHA, Y. N.

Structural Variants of Prolactin: Occurrence and Physiological Significance

Department of Biochemistry and Clinical Physiology, Whittier Institute for Diabetes and Endocrinology La Jolla, California 92037

Correspondence: Address correspondence to: Y. N. Sinha, Ph.D., 8385 Aries Road, San Diego, California 92126.

Abstract

I. Introduction: PROLACTIN (PRL) is one of the most versatile hormones of the pituitary gland in terms of biological actions. More than 100 different and distinct effects of the hormone have been documented (1), ranging from mammary development and initiation of lactation in mammals to osmoregulation in fishes, nesting behavior in birds, and growth and metamorphosis in amphibians. These are far in excess of the reported actions of all other adenohypophyseal hormones combined. But how does a single molecule evoke so many different responses? Studies in the last few years have shown that the hormone exists in several molecular forms, some arising from posttranslational modifications and others from genetically determined factors. Such findings have led to the suggestion that PRL is perhaps a prohormone, which is synthesized as a precursor molecule and then converted to different bioactive forms as it traverses the secretory pathway. The purpose of this review is to provide an account of the recent advances in the characterization of the molecular heterogeneity of PRL and to consider the physiological implications of the structural polymorphism of this polyfunctional hormone. Previous reviews of the subject can be found in Refs. 2–9.

This article has been cited by other articles:

				J. Triebel, M. Huefner, and G. Ramadori Investigation of prolactin-related vasoinhibin in sera from patients with diabetic retinopathy Eur. J. Endocrinol., August 1, 2009; 161(2): 345 - 353. [Abstract] [Full Text] [PDF]

				A. Leanos-Miranda, J. Marquez-Acosta, G. M. Cardenas-Mondragon, Z. L. Chinolla-Arellano, R. Rivera-Leanos, S. Bermejo-Huerta, J. F. Romero-Arauz, G. Alvarez-Jimenez, J. C. Ramos-Leon, and A. Ulloa-Aguirre Urinary Prolactin as a Reliable Marker for Preeclampsia, Its Severity, and the Occurrence of Adverse Pregnancy Outcomes J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2492 - 2499. [Abstract] [Full Text] [PDF]

				N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee What Can We Learn from Rodents about Prolactin in Humans? Endocr. Rev., February 1, 2008; 29(1): 1 - 41. [Abstract] [Full Text] [PDF]

				Z. Kang, G. Y. Bedecarrats, and D. Zadworny Expression Patterns of the Prolactin Receptor Gene in Chicken Lymphoid Tissues During Embryogenesis and Posthatch Period Poult. Sci., November 1, 2007; 86(11): 2404 - 2412. [Abstract] [Full Text] [PDF]

				N. Hattori, Y. Nakayama, K. Kitagawa, T. Li, and C. Inagaki Development of Anti-PRL (Prolactin) Autoantibodies by Homologous PRL in Rats: A Model for Macroprolactinemia Endocrinology, May 1, 2007; 148(5): 2465 - 2470. [Abstract] [Full Text] [PDF]

				S. S. Tworoger, A. H. Eliassen, P. Sluss, and S. E. Hankinson A Prospective Study of Plasma Prolactin Concentrations and Risk of Premenopausal and Postmenopausal Breast Cancer J. Clin. Oncol., April 20, 2007; 25(12): 1482 - 1488. [Abstract] [Full Text] [PDF]

				A. Bachelot and N. Binart Reproductive role of prolactin Reproduction, February 1, 2007; 133(2): 361 - 369. [Abstract] [Full Text] [PDF]

				M. B. Frungieri, S. I. Gonzalez-Calvar, F. Parborell, M. Albrecht, A. Mayerhofer, and R. S. Calandra Cyclooxygenase-2 and Prostaglandin F2{alpha} in Syrian Hamster Leydig Cells: Inhibitory Role on Luteinizing Hormone/Human Chorionic Gonadotropin-Stimulated Testosterone Production Endocrinology, September 1, 2006; 147(9): 4476 - 4485. [Abstract] [Full Text] [PDF]

				N Hattori, Y Nakayama, K Kitagawa, T Ishihara, Y Saiki, and C Inagaki Anti-prolactin (PRL) autoantibody-binding sites (epitopes) on PRL molecule in macroprolactinemia. J. Endocrinol., August 1, 2006; 190(2): 287 - 293. [Abstract] [Full Text] [PDF]

				J L Crawford, B P Thomson, M F Beaumont, and D C Eckery Plasma concentrations of prolactin in brushtail possums (Trichosurus vulpecula) in different physiological states. J. Endocrinol., August 1, 2006; 190(2): 295 - 305. [Abstract] [Full Text] [PDF]

				F E Utama, M J LeBaron, L M Neilson, A S Sultan, A F Parlow, K-U Wagner, and H Rui Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice. J. Endocrinol., March 1, 2006; 188(3): 589 - 601. [Abstract] [Full Text] [PDF]

				E. J. H. Schenck and C. L. Brooks Effects of an S84E Mutation of Bovine Growth Hormone in Transgenic Mice. Experimental Biology and Medicine, March 1, 2006; 231(3): 296 - 302. [Abstract] [Full Text] [PDF]

				J. F. Langenheim, D. Tan, A. M. Walker, and W. Y. Chen Two Wrongs Can Make a Right: Dimers of Prolactin and Growth Hormone Receptor Antagonists Behave as Agonists Mol. Endocrinol., March 1, 2006; 20(3): 661 - 674. [Abstract] [Full Text] [PDF]

				A. Glezer, C. R. J. Soares, J. G. Vieira, D. Giannella-Neto, M. T. C. P. Ribela, V. Goffin, and M. D. Bronstein Human Macroprolactin Displays Low Biological Activity via Its Homologous Receptor in a New Sensitive Bioassay J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1048 - 1055. [Abstract] [Full Text] [PDF]

				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]

				A. Leanos-Miranda and G. Cardenas-Mondragon Serum free prolactin concentrations in patients with systemic lupus erythematosus are associated with lupus activity Rheumatology, January 1, 2006; 45(1): 97 - 101. [Abstract] [Full Text] [PDF]

				C. A. Blake and S. M. Helmke Proteomics of the Anterior Pituitary Gland as a Model for Studying the Physiology of a Heterogeneous Organ Experimental Biology and Medicine, December 1, 2005; 230(11): 793 - 799. [Abstract] [Full Text] [PDF]

				S.-h. Lee, M. Nishino, T. Mazumdar, G. E. Garcia, M. Galfione, F. L. Lee, C. L. Lee, A. Liang, J. Kim, L. Feng, et al. 16-kDa Prolactin Down-Regulates Inducible Nitric Oxide Synthase Expression through Inhibition of the Signal Transducer and Activator of Transcription 1/IFN Regulatory Factor-1 Pathway Cancer Res., September 1, 2005; 65(17): 7984 - 7992. [Abstract] [Full Text] [PDF]

				W. Wu, E. Ginsburg, B. K. Vonderhaar, and A. M. Walker S179D Prolactin Increases Vitamin D Receptor and p21 through Up-regulation of Short 1b Prolactin Receptor in Human Prostate Cancer Cells Cancer Res., August 15, 2005; 65(16): 7509 - 7515. [Abstract] [Full Text] [PDF]

				M. J. Naylor, S. R. Oakes, M. Gardiner-Garden, J. Harris, K. Blazek, T. W. C. Ho, F. C. Li, D. Wynick, A. M. Walker, and C. J. Ormandy Transcriptional Changes Underlying the Secretory Activation Phase of Mammary Gland Development Mol. Endocrinol., July 1, 2005; 19(7): 1868 - 1883. [Abstract] [Full Text] [PDF]

				J. Gibney, T. P. Smith, and T. J. McKenna The Impact on Clinical Practice of Routine Screening for Macroprolactin J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3927 - 3932. [Abstract] [Full Text] [PDF]

				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]

				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]

				M. Lkhider, R. Castino, E. Bouguyon, C. Isidoro, and M. Ollivier-Bousquet Cathepsin D released by lactating rat mammary epithelial cells is involved in prolactin cleavage under physiological conditions J. Cell Sci., October 1, 2004; 117(21): 5155 - 5164. [Abstract] [Full Text] [PDF]

				D. Piwnica, P. Touraine, I. Struman, S. Tabruyn, G. Bolbach, C. Clapp, J. A. Martial, P. A. Kelly, and V. Goffin Cathepsin D Processes Human Prolactin into Multiple 16K-Like N-Terminal Fragments: Study of Their Antiangiogenic Properties and Physiological Relevance Mol. Endocrinol., October 1, 2004; 18(10): 2522 - 2542. [Abstract] [Full Text] [PDF]

				S. S. Tworoger, A. H. Eliassen, B. Rosner, P. Sluss, and S. E. Hankinson Plasma Prolactin Concentrations and Risk of Postmenopausal Breast Cancer Cancer Res., September 15, 2004; 64(18): 6814 - 6819. [Abstract] [Full Text] [PDF]

				M Garcia, M E Colombani-Vidal, C C Zylbersztein, A Testi, J Marcos, A Arturi, J Babini, and H E Scaglia Analysis of molecular heterogeneity of prolactin in human systemic lupus erythematosus Lupus, August 1, 2004; 13(8): 575 - 583. [Abstract] [PDF]

				M. D. Schroeder, J. L. Brockman, A. M. Walker, and L. A. Schuler Inhibition of Prolactin (PRL)-Induced Proliferative Signals in Breast Cancer Cells by a Molecular Mimic of Phosphorylated PRL, S179D-PRL Endocrinology, December 1, 2003; 144(12): 5300 - 5307. [Abstract] [Full Text] [PDF]

				C. V. Clevenger, P. A. Furth, S. E. Hankinson, and L. A. Schuler The Role of Prolactin in Mammary Carcinoma Endocr. Rev., February 1, 2003; 24(1): 1 - 27. [Abstract] [Full Text] [PDF]

				J. E. B. Cavaco, C. R.A. Santos, P. M. Ingleton, A. V.M. Canario, and D. M. Power Quantification of Prolactin (PRL) and PRL Receptor Messenger RNA in Gilthead Seabream (Sparus aurata) after Treatment with Estradiol-17{beta} Biol Reprod, February 1, 2003; 68(2): 588 - 594. [Abstract] [Full Text] [PDF]

				J. Kim, W. Luo, D.-T. Chen, K. Earley, J. Tunstead, L.-Y. Yu-Lee, and S.-H. Lin Antitumor Activity of the 16-kDa Prolactin Fragment in Prostate Cancer Cancer Res., January 15, 2003; 63(2): 386 - 393. [Abstract] [Full Text] [PDF]

				A Stevens, D W Ray, J Worthington, and J R. Davis Polymorphisms of the human prolactin gene--implications for production of lymphocyte prolactin and systemic lupus erythematosus Lupus, October 1, 2001; 10(10): 676 - 683. [Abstract] [PDF]

				S. Bernichtein, S. Kinet, S. Jeay, M. Llovera, D. Madern, J. A. Martial, P. A. Kelly, and V. Goffin S179D-Human PRL, a Pseudophosphorylated Human PRL Analog, Is an Agonist and Not an Antagonist Endocrinology, September 1, 2001; 142(9): 3950 - 3963. [Abstract] [Full Text] [PDF]

				X. Xu, E. Kreye, C. B. Kuo, and A. M. Walker A Molecular Mimic of Phosphorylated Prolactin Markedly Reduced Tumor Incidence and Size When DU145 Human Prostate Cancer Cells Were Grown in Nude Mice Cancer Res., August 1, 2001; 61(16): 6098 - 6104. [Abstract] [Full Text] [PDF]

				A. Leanos-Miranda, D. Pascoe-Lira, K. A. Chavez-Rueda, and F. Blanco-Favela Persistence of Macroprolactinemia Due to Antiprolactin Autoantibody before, during, and after Pregnancy in a Woman with Systemic Lupus Erythematosus J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2619 - 2624. [Abstract] [Full Text] [PDF]

				A Leanos-Miranda, D Pascoe-Lira, K A Chavez-Rueda, and F Blanco-Favela Detection of macroprolactinemia with the polyethylene glycol precipitation test in systemic lupus erythematosus patients with hyperprolactinemia Lupus, May 1, 2001; 10(5): 340 - 345. [Abstract] [PDF]

				D. Pascoe-Lira, G. Duran-Reyes, I. Contreras-Hernández, L. Manuel-Apolinar, F. Blanco-Favela, and A. Leaños-Miranda Frequency of Macroprolactinemia Due to Autoantibodies against Prolactin in Pregnant Women J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 924 - 929. [Abstract] [Full Text]

				M Lkhider, B Petridou, A Aubourg, and M Ollivier-Bousquet Prolactin signalling to milk protein secretion but not to gene expression depends on the integrity of the Golgi region J. Cell Sci., January 5, 2001; 114(10): 1883 - 1891. [Abstract] [PDF]

				D. Coss, L. Yang, C. B. Kuo, X. Xu, R. A. Luben, and A. M. Walker Effects of prolactin on osteoblast alkaline phosphatase and bone formation in the developing rat Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1216 - E1225. [Abstract] [Full Text] [PDF]

				M. E. Freeman, B. Kanyicska, A. Lerant, and G. Nagy Prolactin: Structure, Function, and Regulation of Secretion Physiol Rev, October 1, 2000; 80(4): 1523 - 1631. [Abstract] [Full Text] [PDF]

				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]

				D. Coss, C. B. Kuo, L. Yang, P. Ingleton, R. Luben, and A. M. Walker Dissociation of Janus Kinase 2 and Signal Transducer and Activator of Transcription 5 Activation after Treatment of Nb2 Cells with a Molecular Mimic of Phosphorylated Prolactin Endocrinology, November 1, 1999; 140(11): 5087 - 5094. [Abstract] [Full Text]

				S. Kinet, S. Bernichtein, P. A. Kelly, J. A. Martial, and V. Goffin Biological Properties of Human Prolactin Analogs Depend Not Only on Global Hormone Affinity, but Also on the Relative Affinities of Both Receptor Binding Sites J. Biol. Chem., September 10, 1999; 274(37): 26033 - 26043. [Abstract] [Full Text] [PDF]

				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]

				G. Bédécarrats, D. Guémené, C. Morvan, U. Kühnlein, and D. Zadworny Quantification of Prolactin Messenger Ribonucleic Acid, Pituitary Content and Plasma Levels of Prolactin, and Detection of Immunoreactive Isoforms of Prolactin in Pituitaries from Turkey Embryos During Ontogeny Biol Reprod, September 1, 1999; 61(3): 757 - 763. [Abstract] [Full Text]

				S. E. Hankinson, W. C. Willett, D. S. Michaud, J. E. Manson, G. A. Colditz, C. Longcope, B. Rosner, and F. E. Speizer Plasma Prolactin Levels and Subsequent Risk of Breast Cancer in Postmenopausal Women J Natl Cancer Inst, April 7, 1999; 91(7): 629 - 634. [Abstract] [Full Text] [PDF]

				I. Struman, F. Bentzien, H. Lee, V. Mainfroid, G. D'Angelo, V. Goffin, R. I. Weiner, and J. A. Martial Opposing actions of intact and N-terminal fragments of the human prolactin/growth hormone family members on angiogenesis: An efficient mechanism for the regulation of angiogenesis PNAS, February 16, 1999; 96(4): 1246 - 1251. [Abstract] [Full Text] [PDF]

				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]

				L. Muller, R. Picart, A. Barret, N. G. Seidah, and C. Tougard Immunocytochemical Localization of the Prohormone Convertases PC1 and PC2 in Rat Prolactin Cells J. Histochem. Cytochem., January 1, 1998; 46(1): 101 - 108. [Abstract] [Full Text]

				F. Larrea, A. Martinez-Castillo, V. Cabrera, J. Alcocer-Varela, G. Queipo, C. Carino, and D. Alarcon-Segovia A Bioactive 60-Kilodalton Prolactin Species Is Preferentially Secreted in Cultures of Mitogen-Stimulated and Nonstimulated Peripheral Blood Mononuclear Cells from Subjects with Systemic Lupus Erythematosus J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3664 - 3669. [Abstract] [Full Text] [PDF]

				F. C. Peterson and C. L. Brooks Identification of a Motif Associated with the Lactogenic Actions of Human Growth Hormone J. Biol. Chem., August 22, 1997; 272(34): 21444 - 21448. [Abstract] [Full Text] [PDF]

				P. M. Maciejewski, F. C. Peterson, P. J. Anderson, and C. L. Brooks Mutation of Serine 90 to Glutamic Acid Mimics Phosphorylation of Bovine Prolactin J. Biol. Chem., November 17, 1995; 270(46): 27661 - 27665. [Abstract] [Full Text] [PDF]