Clinical Neuroendocrinology and Neuroendocrine Tumors

Estradiol Enables Cortisol to Act Directly upon the Pituitary to Suppress Pituitary Responsiveness to GnRH in Sheep
B.N. Pierce, C.A. Stackpole, K.M. Breen, I.J. Clarke, F.J. Karsch, E.T.A. Rivalland, A.I. Turner, D.J. Caddy, E.R. Wagenmaker, A.E. Oakley, A.J. Tilbrook

Department of Physiology, Monash University, Monash, Vic., Australia; Reproductive Sciences Program and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Mich., USA

Address of Corresponding Author

Neuroendocrinology 2009;89:86-97 (DOI: 10.1159/000151543)

  Key Words

• Cortisol
• Luteinizing hormone
• Estradiol
• Hypothalamo-pituitary disconnection

  Abstract

We have shown that cortisol infusion reduced the luteinizing hormone (LH) response to fixed hourly GnRH injections in ovariectomized ewes treated with estradiol during the non-breeding season (pituitary-clamp model). In contrast, cortisol did not affect the response to 2 hourly invariant GnRH injections in hypothalamo-pituitary disconnected ovariectomized ewes during the breeding season. To understand the differing results in these animal models and to determine if cortisol can act directly at the pituitary to suppress responsiveness to GnRH, we investigated the importance of the frequency of GnRH stimulus, the presence of estradiol and stage of the circannual breeding season. In experiment 1, during the non-breeding season, ovariectomized ewes were treated with estradiol, and pulsatile LH secretion was restored with i.v. GnRH injections either hourly or 2 hourly in the presence or absence of exogenous cortisol. Experiments 2 and 3 were conducted in hypothalamo-pituitary disconnected ovariectomized ewes in which GnRH was injected i.v. every 2 h. Experiment 2 was conducted during the non-breeding season and saline or cortisol was infused for 30 h in a cross-over design. Experiment 3 was conducted during the non-breeding and breeding seasons and saline or cortisol was infused for 30 h in the absence and presence of estradiol using a cross-over design. Samples were taken from all animals to measure plasma LH. LH pulse amplitude was reduced by cortisol in the pituitary clamp model with no difference between the hourly and 2-hourly GnRH pulse mode. In the absence of estradiol, there was no effect of cortisol on LH pulse amplitude in GnRH-replaced ovariectomized hypothalamo-pituitary disconnected ewes in either season. The LH pulse amplitude was reduced in both seasons in experiment 3 when cortisol was infused during estradiol treatment. We conclude that the ability of cortisol to reduce LH secretion does not depend upon the frequency of GnRH stimulus and that estradiol enables cortisol to act directly on the pituitary of ovariectomized hypothalamo-pituitary disconnected ewes to suppress the responsiveness to GnRH; this effect occurs in the breeding and non-breeding seasons.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Alan J. Tilbrook
Department of Physiology, PO Box 13F
Monash University
Monash, Vic. 3800 (Australia)
Tel. +61 3 9909 2551, Fax +61 3 9905 2547, E-Mail alan.tilbrook@med.monash.edu.au

  Article Information

This work was supported by NIH grants HD30773, NIH-T32-07048, NIH-T32-08322 and Monash University.

Received: December 11, 2007
Accepted after revision: April 23, 2008
Published online: August 19, 2008
Number of Print Pages : 12
Number of Figures : 6, Number of Tables : 0, Number of References : 39