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 Wagenmaker, E. R. Articles by Karsch, F. J. Search for Related Content PubMed PubMed Citation Articles by Wagenmaker, E. R. Articles by Karsch, F. J.

Psychosocial Stress Inhibits Amplitude of Gonadotropin-Releasing Hormone Pulses Independent of Cortisol Action on the Type II Glucocorticoid Receptor

Department of Molecular and Integrative Physiology and Reproductive Sciences Program (E.R.W., K.M.B., A.E.O., F.J.K.), University of Michigan, Ann Arbor, Michigan, 48109-0404; and Department of Physiology (A.J.T.), Monash University, Clayton, Victoria 3800, Australia

Address all correspondence and requests for reprints to: Fred J. Karsch, Department of Molecular and Integrative Physiology, University of Michigan, Medical Sciences II, Room 7712B, Ann Arbor, Michigan 48109-5622. E-mail: fjkarsch{at}umich.edu.

Our laboratory has developed a paradigm of psychosocial stress (sequential layering of isolation, blindfold, and predator cues) that robustly elevates cortisol secretion and decreases LH pulse amplitude in ovariectomized ewes. This decrease in LH pulse amplitude is due, at least in part, to a reduction in pituitary responsiveness to GnRH, caused by cortisol acting via the type II glucocorticoid receptor (GR). The first experiment of the current study aimed to determine whether this layered psychosocial stress also inhibits pulsatile GnRH release into pituitary portal blood. The stress paradigm significantly reduced GnRH pulse amplitude compared with nonstressed ovariectomized ewes. The second experiment tested if this stress-induced decrease in GnRH pulse amplitude is mediated by cortisol action on the type II GR. Ovariectomized ewes were allocated to three groups: nonstress control, stress, and stress plus the type II GR antagonist RU486. The layered psychosocial stress paradigm decreased GnRH and LH pulse amplitude compared with nonstress controls. Importantly, the stress also lowered GnRH pulse amplitude to a comparable extent in ewes in which cortisol action via the type II GR was antagonized. Therefore, we conclude that psychosocial stress reduces the amplitude of GnRH pulses independent of cortisol action on the type II GR. The present findings, combined with our recent observations, suggest that the mechanisms by which psychosocial stress inhibits reproductive neuroendocrine activity at the hypothalamic and pituitary levels are fundamentally different.

This article has been cited by other articles:

				M. J. P. Fraites, R. L. Cooper, A. Buckalew, S. Jayaraman, L. Mills, and S. C. Laws Characterization of the Hypothalamic-Pituitary-Adrenal Axis Response to Atrazine and Metabolites in the Female Rat Toxicol. Sci., November 1, 2009; 112(1): 88 - 99. [Abstract] [Full Text] [PDF]

				A. E. Oakley, K. M. Breen, A. J. Tilbrook, E. R. Wagenmaker, and F. J. Karsch Role of Estradiol in Cortisol-Induced Reduction of Luteinizing Hormone Pulse Frequency Endocrinology, June 1, 2009; 150(6): 2775 - 2782. [Abstract] [Full Text] [PDF]