Journal of Clinical Endocrinology & Metabolism, Vol 61, 842-845, Copyright © 1985 by Endocrine Society

ARTICLES

Evidence for a role of endogenous estrogen in the hypothalamic control of gonadotropin secretion in men

SJ Winters and P Troen

To examine the mechanism by which endogenous estrogens inhibit gonadotropin secretion in men, blood samples were drawn every 10 min for 12 h in five men before and at the completion of 3 weeks of treatment with the estrogen antagonist clomiphene citrate (50 mg twice daily). Samples were analyzed for LH and alpha-subunit by RIA. Clomiphene produced a 3-fold rise in circulating LH levels, which was associated with a 80% increase in pulse frequency and a 70% increase in pulse amplitude. Immunoreactive alpha-subunit secretion was also pulsatile before and after clomiphene treatment. Mean alpha-levels rose 70%, together with a 39% increase in pulse frequency and a 41% increase in pulse amplitude. Circulating testosterone and estradiol levels increased 2-fold and FSH levels increased 3-fold after clomiphene treatment. Insofar as each LH and uncombined alpha-subunit pulse reflects a LHRH secretory episode, our data indicate that endogenous estrogens tonically restrain the hypothalamic release of LHRH. From these results and those of previous studies, we conclude that estrogens as well as androgens are important in the testicular feedback inhibition of the hypothalamic oscillator that governs pulsatile gonadotropin secretion.

This article has been cited by other articles:

				N. Pitteloud, A. A. Dwyer, S. DeCruz, H. Lee, P. A. Boepple, W. F. Crowley Jr., and F. J. Hayes Inhibition of Luteinizing Hormone Secretion by Testosterone in Men Requires Aromatization for Its Pituitary But Not Its Hypothalamic Effects: Evidence from the Tandem Study of Normal and Gonadotropin-Releasing Hormone-Deficient Men J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 784 - 791. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis and A. Iranmanesh Short-Term Aromatase-Enzyme Blockade Unmasks Impaired Feedback Adaptations in Luteinizing Hormone and Testosterone Secretion in Older Men J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 211 - 218. [Abstract] [Full Text] [PDF]

				A. Tiitinen and M. Valimaki Primary Infertility in 45-Year-Old Man with Untreated 21-Hydroxylase Deficiency: Successful Outcome with Glucocorticoid Therapy J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2442 - 2445. [Abstract] [Full Text] [PDF]

				J. M. Kuhn, H. Lefebvre, C. Duparc, A. Pellerin, J. P. Luton, and G. Strauch Cosecretion of Estrogen and Inhibin B by a Feminizing Adrenocortical Adenoma: Impact on Gonadotropin Secretion J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2367 - 2375. [Abstract] [Full Text] [PDF]

				G. Van den Berghe, F. Weekers, R. C. Baxter, P. Wouters, A. Iranmanesh, R. Bouillon, and J. D. Veldhuis Five-Day Pulsatile Gonadotropin-Releasing Hormone Administration Unveils Combined Hypothalamic-Pituitary-Gonadal Defects Underlying Profound Hypoandrogenism in Men with Prolonged Critical Illness J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3217 - 3226. [Abstract] [Full Text] [PDF]

				J. A. Schnorr, M. J. Bray, and J. D. Veldhuis Aromatization Mediates Testosterone's Short-Term Feedback Restraint of 24-Hour Endogenously Driven and Acute Exogenous Gonadotropin-Releasing Hormone-Stimulated Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in Young Men J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2600 - 2606. [Abstract] [Full Text] [PDF]

				M.-L. Kottler, S. Chauvin, N. Lahlou, C. E. Harris, C. J. Johnston, J.-P. Lagarde, P. Bouchard, N. R. Farid, and R. Counis A New Compound Heterozygous Mutation of the Gonadotropin-Releasing Hormone Receptor (L314X, Q106R) in a Woman with Complete Hypogonadotropic Hypogonadism: Chronic Estrogen Administration Amplifies the Gonadotropin Defect J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3002 - 3008. [Abstract] [Full Text]

				F. J. Hayes, S. B. Seminara, S. DeCruz, P. A. Boepple, and W. F. Crowley Jr. Aromatase Inhibition in the Human Male Reveals a Hypothalamic Site of Estrogen Feedback J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3027 - 3035. [Abstract] [Full Text]

				S. Kawakami and S. J. Winters Regulation of Lutenizing Hormone Secretion and Subunit Messenger Ribonucleic Acid Expression by Gonadal Steroids in Perifused Pituitary Cells from Male Monkeys and Rats Endocrinology, August 1, 1999; 140(8): 3587 - 3593. [Abstract] [Full Text]

				C. Wang, N. G. Berman, J. D. Veldhuis, T. Der, V. McDonald, B. Steiner, and R. S. Swerdloff Graded Testosterone Infusions Distinguish Gonadotropin Negative-Feedback Responsiveness in Asian and White Men--A Clinical Research Center Study J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 870 - 876. [Abstract] [Full Text]