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Cortisol Reduces Gonadotropin-Releasing Hormone Pulse Frequency in Follicular Phase Ewes: Influence of Ovarian Steroids

Department of Molecular and Integrative Physiology and Reproductive Sciences Program (A.E.O., K.M.B., F.J.K., E.R.W.), University of Michigan, Ann Arbor, Michigan 48109-0404; and Department of Physiology (I.J.C., 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, 1301 East Catherine Street, Room 7744 Med Sci II 0622, Ann Arbor, Michigan 48109. E-mail: fjkarsch{at}umich.edu.

Stress-like elevations in plasma glucocorticoids suppress gonadotropin secretion and can disrupt ovarian cyclicity. In sheep, cortisol acts at the pituitary to reduce responsiveness to GnRH but does not affect GnRH pulse frequency in the absence of ovarian hormones. However, in ewes during the follicular phase of the estrous cycle, cortisol reduces LH pulse frequency. To test the hypothesis that cortisol reduces GnRH pulse frequency in the presence of ovarian steroids, the effect of cortisol on GnRH secretion was monitored directly in pituitary portal blood of follicular phase sheep in the presence and absence of a cortisol treatment that elevated plasma cortisol to a level observed during stress. An acute (6 h) cortisol increase in the midfollicular phase did not lower GnRH pulse frequency. However, a more prolonged (27 h) increase in cortisol beginning just before the decrease in progesterone reduced GnRH pulse frequency by 45% and delayed the preovulatory LH surge by 10 h. To determine whether the gonadal steroid milieu of the follicular phase enables cortisol to reduce GnRH pulse frequency, GnRH was monitored in ovariectomized ewes treated with estradiol and progesterone to create an artificial follicular phase. A sustained increment in plasma cortisol reduced GnRH pulse frequency by 70% in this artificial follicular phase, in contrast to the lack of an effect in untreated ovariectomized ewes as seen previously. Thus, a sustained stress-like level of cortisol suppresses GnRH pulse frequency in follicular phase ewes, and this appears to be dependent upon the presence of ovarian steroids.

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