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Rapid in Vivo Effects of Estradiol-17ß in Ovine Pituitary Gonadotropes Are Displayed by Phosphorylation of Extracellularly Regulated Kinase, Serine/Threonine Kinase, and 3',5'-Cyclic Adenosine 5'-Monophosphate-Responsive Element-Binding Protein

Department of Physiology, Monash University, Clayton, Victoria 3800, Australia

Address all correspondence and requests for reprints to: Prof. Iain J. Clarke, Department of Physiology, Monash University, P.O. Box 13 F, Clayton, Victoria 3880, Australia. E-mail: Iain.Clarke{at}med.monash.edu.au.

We have determined the time course of phosphorylation of MAPK/ERK, cAMP-responsive element-binding protein (CREB), and serine/threonine kinase (Akt) in ovine pituitary gonadotropes after in vivo injection (iv) of either 25 µg estradiol-17ß (E17ß) or vehicle. In ovariectomized ewes, E17ß increased the number of gonadotropes expressing phosphorylated (p)ERK-1/2 and pCREB immunoreactivity (-IR) within 90 min, as assessed by immunohistochemistry. By Western blot, we also showed that pERK-1/2, pCREB, and pAkt (ser 473) proteins were up-regulated by E17ß. In ovariectomized, hypothalamo-pituitary-disconnected animals, gonadotrope function was restored with hourly GnRH pulses (iv), and E17ß injection (iv) reduced LH response within 1 h. Immunohistochemistry showed that E17ß increased pERK-1/2-IR in gonadotropes within 15 min and peak response at 60 min. The number of cells immunoreactive for pCREB was greater in E17ß-treated animals than in vehicle-injected controls at 60 and 90 min. Western blot revealed a pERK-1/2 response within 15 min and pCREB response at 30 min. Up-regulation of pAkt occurred within 60 min of E17ß treatment. Thus, rapid effects of E17ß on gonadotropes involve phosphorylation of second messenger proteins with a time course that may relate to the rapid negative feedback effect to reduce responsiveness to GnRH.

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				J. Iqbal, O. Latchoumanin, I. P. Sari, R. J. Lang, H. A. Coleman, H. C. Parkington, and I. J. Clarke Estradiol-17{beta} Inhibits Gonadotropin-Releasing Hormone-Induced Ca2+ in Gonadotropes to Regulate Negative Feedback on Luteinizing Hormone Release Endocrinology, September 1, 2009; 150(9): 4213 - 4220. [Abstract] [Full Text] [PDF]