This Article Full Text 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 Ma, F. Y. Articles by Bunn, S. J. Search for Related Content PubMed PubMed Citation Articles by Ma, F. Y. Articles by Bunn, S. J.

Prolactin Specifically Activates Signal Transducer and Activator of Transcription 5b in Neuroendocrine Dopaminergic Neurons

Center for Neuroendocrinology and Department of Anatomy and Structural Biology, University of Otago School of Medical Sciences (F.Y.M., G.M.A., T.D.G., D.R.G., S.J.B.), Dunedin 9001, New Zealand; and Institut National de la Santé et de la Recherche Médicale, Unité 584, Molecular Endocrinology, Faculté de Médecine Necker (V.G.), 75730 Paris, France

Address all correspondence and requests for reprints to: Dr. Stephen Bunn, Center for Neuroendocrinology and Department of Anatomy and Structural Biology, University of Otago School of Medical Sciences, P.O. Box 913, Dunedin 9001, New Zealand. E-mail: stephen.bunn{at}stonebow.otago.ac.nz.

The hypothalamic neuroendocrine dopaminergic (NEDA) neurons are crucial in regulating prolactin secretion from the anterior pituitary. Rising prolactin concentrations stimulate these neurons to secrete dopamine, which acts via the pituitary portal vasculature to inhibit additional prolactin release. Prolactin is known to activate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways in other cell types, including neurons. The possible role of JAK-STAT signaling in NEDA neurons has therefore been examined in this study using fetal rat mediobasal hypothalamic cell cultures and an adult rat in vivo preparation. Cultured cells expressing the dopamine synthesizing enzyme tyrosine hydroxylase (TH) responded to prolactin with a time-dependent increase in phospho-STAT5, but not phospho-STAT1 or phospho-STAT3, nuclear labeling. This response was inhibited by the prolactin receptor antagonist 1–9-G129R-human prolactin and the JAK inhibitor AG490, but was unaffected by selected serine/threonine kinase inhibitors (H89, KN-93, bisindolymaleimide, or PD98059). Antibodies selective for STAT5a or STAT5b indicated that the response was restricted to STAT5b, with the number of TH cells displaying STAT5b nuclear immunoreactivity rising from less than 10% under basal conditions to approximately 70% after prolactin stimulation. STAT5a nuclear labeling remained unchanged at 6–10% of TH-positive cells. STAT5b selectivity was confirmed in vivo, where the injection of prolactin into bromocriptine-treated rats stimulated a time-dependent increase in STAT5b, but not STAT5a, nuclear staining in the TH-expressing neurons in the arcuate nucleus. These results extend our previous findings with STAT5b-deficient mice and strongly suggest that in NEDA neurons, prolactin signaling via the JAK/STAT pathway is mediated exclusively by STAT5b.

This article has been cited by other articles:

				C. V. Helena, D. T. McKee, R. Bertram, A. M. Walker, and M. E. Freeman The Rhythmic Secretion of Mating-Induced Prolactin Secretion Is Controlled by Prolactin Acting Centrally Endocrinology, July 1, 2009; 150(7): 3245 - 3251. [Abstract] [Full Text] [PDF]

				A. M. Mikheev, T. Nabekura, A. Kaddoumi, T. K. Bammler, R. Govindarajan, M. F. Hebert, and J. D. Unadkat Profiling Gene Expression in Human Placentae of Different Gestational Ages: An OPRU* Network and UW SCOR Study Reproductive Sciences, November 1, 2008; 15(9): 866 - 877. [Abstract] [PDF]

				T. Misztal, K. Gorski, D. Tomaszewska-Zaremba, E. Molik, and K. Romanowicz Identification of salsolinol in the mediobasal hypothalamus of lactating ewes and its relation to suckling-induced prolactin and GH release J. Endocrinol., July 1, 2008; 198(1): 83 - 89. [Abstract] [Full Text] [PDF]

				P. Fitzgerald and T. G Dinan Prolactin and dopamine: What is the connection? A Review Article J Psychopharmacol, March 1, 2008; 22(2_suppl): 12 - 19. [Abstract] [PDF]

				J.-B. Jomain, E. Tallet, I. Broutin, S. Hoos, J. van Agthoven, A. Ducruix, P. A. Kelly, B. B. Kragelund, P. England, and V. Goffin Structural and Thermodynamic Bases for the Design of Pure Prolactin Receptor Antagonists: X-RAY STRUCTURE OF Del1-9-G129R-hPRL J. Biol. Chem., November 9, 2007; 282(45): 33118 - 33131. [Abstract] [Full Text] [PDF]

				D. R. Grattan, C. L. Jasoni, X. Liu, G. M. Anderson, and A. E. Herbison Prolactin Regulation of Gonadotropin-Releasing Hormone Neurons to Suppress Luteinizing Hormone Secretion in Mice Endocrinology, September 1, 2007; 148(9): 4344 - 4351. [Abstract] [Full Text] [PDF]

				A. Bernasconi, R. Marino, A. Ribas, J. Rossi, M. Ciaccio, M. Oleastro, A. Ornani, R. Paz, M. A. Rivarola, M. Zelazko, et al. Characterization of Immunodeficiency in a Patient With Growth Hormone Insensitivity Secondary to a Novel STAT5b Gene Mutation Pediatrics, November 1, 2006; 118(5): e1584 - e1592. [Abstract] [Full Text] [PDF]

				G. M. Anderson, D. R. Grattan, W. van den Ancker, and R. S. Bridges Reproductive Experience Increases Prolactin Responsiveness in the Medial Preoptic Area and Arcuate Nucleus of Female Rats Endocrinology, October 1, 2006; 147(10): 4688 - 4694. [Abstract] [Full Text] [PDF]

				G. M. Anderson, P. Beijer, A. S. Bang, M. A. Fenwick, S. J. Bunn, and D. R. Grattan Suppression of Prolactin-Induced Signal Transducer and Activator of Transcription 5b Signaling and Induction of Suppressors of Cytokine Signaling Messenger Ribonucleic Acid in the Hypothalamic Arcuate Nucleus of the Rat during Late Pregnancy and Lactation Endocrinology, October 1, 2006; 147(10): 4996 - 5005. [Abstract] [Full Text] [PDF]