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Progesterone Blocks the Estradiol-Stimulated Luteinizing Hormone Surge by Disrupting Activation in Response to a Stimulatory Estradiol Signal in the Ewe¹

^a Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge CB2 4AT, United Kingdom ^b Department of Veterinary Preclinical Studies, University of Glasgow Veterinary School, Glasgow G61 1QH, United Kingdom

The preovulatory surges of GnRH and LH are activated by increased concentrations of circulating estradiol, but ovulation is blocked when progesterone concentrations are elevated. Although it is has been shown that this action of progesterone is due to a central inhibition of the GnRH surge, the mechanisms that underlie the blockade of the GnRH surge are poorly understood. In this study we investigated whether progesterone can block the estradiol-dependent activation stage of the GnRH surge induction process, and thus prevent expression of the LH surge. The results demonstrated that exposure to progesterone for half or the full duration of the activation stage can prevent the stimulation of LH surges by estradiol (experiment 1), whereas exposure to progesterone midway though a period of estradiol exposure, which in itself is sufficient to activate the surge, did not block the LH surge (experiment 2). These results suggest that progesterone 1) disrupts activation of the surge induction system in response to a stimulatory estradiol signal and 2) does not compromise the ability of animals to respond to a stimulatory estradiol signal applied immediately after progesterone exposure. Because the disruptive effects of activated progesterone in response to estradiol are rapid but transient, it may be that progesterone directly interferes with the activation of estradiol-responsive neural systems to block the GnRH/LH surge.

First decision: 1 September 2001.

¹ Preliminary findings were presented at the 82nd Annual Meeting of the Endocrine Society (Toronto, Canada), abstract 545. This study was supported by the BBSRC, Wellcome Trust grant (060203). T.A.R. was supported by the Cambridge Commonwealth Trust, NRF (South Africa) and by the trustees of the Elsie Ballot Memorial Scholarship.

² Correspondence: Neil P. Evans, Division of Veterinary Physiology, Department of Veterinary Preclinical Studies, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, U.K. FAX: 44 141 330 5797; n.evans{at}vet.gla.ac.uk

³ Current address: Department of Physiology and Biophysics, University of Miami Medical School, 1600 NW 10th St., Miami, FL 33136

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