This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 PERMEZEL, J. M. Articles by COOKE, I. D. Search for Related Content PubMed PubMed Citation Articles by PERMEZEL, J. M. Articles by COOKE, I. D.

Acute Effects of Progesterone and the Antiprogestin RU 486 on Gonadotropin Secretion in the Follicular Phase of the Menstrual Cycle^*

J. MICHAEL PERMEZEL, ELIZABETH A. LENTON, IAN ROBERTS and IAN D. COOKE

Harris Birthright Centre for Reproductive Biology and University of Sheffield (J.M.P., E.A.L., I.D.C.) Sheffield, United Kingdom
Roussel Laboratories Ltd. Uxbridge, Middlesex, United Kingdom

Address all correspondence and requests for reprints to: J. M. H. Permezel, University Department of Obstetrics and Gynaecology, Royal Women’s Hospital, Grattan Street, Carlton, Victoria 3053, Australia.

Considerable controversy still exists concerning the role of progesterone in the initiation of the midcycle gonadotropin surge in humans, We, therefore, carried out a prospective randomized study to determine the potential of progesterone to initiate a gonadotropin surge and the acute effects of a potent progesterone antagonist (RU 486) on follicular phase gonadotropin secretion in normal women.

The women underwent frequent blood sampling for 4 in the midfollicular (day 6) or late follicular phase (day 10). They then received either progesterone (10 mg, im) or RU 486 (10 or 100 mg, orally), and blood sampling was continued for an additional 8 h. Four women received each of the drug regimens in the early follicular phase, and four received each regimen in the late follicular phase. Two additional women were studied as control subjects at each stage of the cycle.

Progesterone administration in the mid- and late follicular phases resulted in an acute increase in plasma LH and FSH concentrations, and the increases correlated with the base line plasma estradiol concentrations (P < 0.05). In contrast to progesterone, the women who received RU 486 in the mid- and late follicular phases had a reduction in plasma LH and FSH concentrations after drug administration. The response in the midfollicular phase was considerably less than that in the late follicular phase, and the extent of the response correlated with the baseline plasma estradiol concentrations (P < 0.005). The changes were similar in response to both RU 486 doses.

We conclude that progesterone can initiate a gonadotropin surge in the late follicular phase of the menstrual cycle. The inhibitory effect of the progesterone antagonist RU 486 suggests that a positive feedback mechanism involving progesterone may be influential some time before the surge onset.

^* This work was supported by Roussel Laboratories Ltd. (Uxbridge, Middlesex, United Kingdom).

Current address: Department of Biochemistry, University of Surrey, Guildford, Surrey, United Kingdom.

Received August 26, 1988.

This article has been cited by other articles:

				N. Chabbert-Buffet, G. Meduri, P. Bouchard, and I. M. Spitz Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications Hum. Reprod. Update, May 1, 2005; 11(3): 293 - 307. [Abstract] [Full Text] [PDF]

				K. Gemzell-Danielsson and L. Marions Mechanisms of action of mifepristone and levonorgestrel when used for emergency contraception Hum. Reprod. Update, July 1, 2004; 10(4): 341 - 348. [Abstract] [Full Text] [PDF]

				P. Stratton, B. Hartog, N. Hajizadeh, J. Piquion, D. Sutherland, M. Merino, Y. J. Lee, and L. K. Nieman A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women Hum. Reprod., May 1, 2000; 15(5): 1092 - 1099. [Abstract] [Full Text] [PDF]

				E. Xiao, L. Xia-Zhang, D. Shanen, and M. Ferin Tonic Support of Luteinizing Hormone Secretion by Adrenal Progesterone in the Ovariectomized Monkey Replaced with Midfollicular Phase Levels of Estradiol J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2233 - 2238. [Abstract] [Full Text] [PDF]

				I. M. Spitz and C.W. Bardin Mifepristone (RU 486) -- A Modulator of Progestin and Glucocorticoid Action N. Engl. J. Med., August 5, 1993; 329(6): 404 - 412. [Full Text]