Journal of Clinical Endocrinology & Metabolism, Vol 64, 1179-1186, Copyright © 1987 by Endocrine Society

ARTICLES

Effects of increasing the frequency of low doses of gonadotropin- releasing hormone (GnRH) on gonadotropin secretion in GnRH-deficient men

DI Spratt, JS Finkelstein, JP Butler, TM Badger and WF Crowley Jr

The effects of increasing the frequency of pulsatile GnRH administration on LH and FSH responsiveness were studied in five GnRH- deficient men who had achieved normal sex steroid levels during prior long term GnRH replacement. Intravenous doses of GnRH were employed that had previously been demonstrated to produce LH and FSH levels in each subject similar to those in normal men. Both acute and chronic changes in pituitary responses were studied after progressive increases in GnRH frequency (from every 120 to 60 min, from 60 to 30 min, and from 30 to 15 min) during three 12-h admissions, each separated by 7 days. During the two intervals between the studies GnRH frequency was 60 and 30 min, respectively. Pituitary responses were characterized by determining the mean serum LH and FSH levels, LH pulse amplitudes, and mean LH and FSH levels which were normalized for the frequency of GnRH administration (nLH and nFSH). As the frequency of GnRH stimulation was increased acutely, mean serum LH levels rose progressively, in contrast to both LH pulse amplitude and nLH levels which decreased, while serum testosterone (T) concentrations remained constant. No further evidence of gonadotroph desensitization occurred after chronic GnRH administration at either 60- or 30-min intervals. At higher frequencies of GnRH stimulation, discrete pulses of LH were not always apparent after injections of GnRH, and in two men, marked destabilization of the gonadotroph responses occurred. Even without detectable LH pulses, serum T levels did not decline during administration of GnRH at intervals as rapid as 15 min. In contrast, there was no change in mean FSH concentrations, although nFSH values decreased progressively as the GnRH frequency was increased. nFSH levels fell to a greater degree than nLH after each increase in GnRH frequency. Thus, pituitary gonadotroph responsiveness to a fixed dose of GnRH decreased as the frequency of GnRH stimulation increased. FSH responsiveness decreased to a greater degree than did LH. Gonadotropin secretory responses are destabilized at higher frequencies of GnRH administration. Pulsatile LH stimulation of the testes does not appear necessary to maintain T secretion.

This article has been cited by other articles:

				S.K. Blank, C.R. McCartney, and J.C. Marshall The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome Hum. Reprod. Update, July 1, 2006; 12(4): 351 - 361. [Abstract] [Full Text] [PDF]

				R. V. Mehta, K. S. Patel, M. S. Coffler, M. H. Dahan, R. Y. Yoo, J. S. Archer, P. J. Malcom, and R. J. Chang Luteinizing Hormone Secretion Is Not Influenced by Insulin Infusion in Women with Polycystic Ovary Syndrome Despite Improved Insulin Sensitivity during Pioglitazone Treatment J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2136 - 2141. [Abstract] [Full Text] [PDF]

				J. E. Hall, J. P. Sullivan, and G. S. Richardson Brief Wake Episodes Modulate Sleep-Inhibited Luteinizing Hormone Secretion in the Early Follicular Phase J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2050 - 2055. [Abstract] [Full Text] [PDF]

				S. J Winters and J. P Moore Intra-pituitary regulation of gonadotrophs in male rodents and primates Reproduction, July 1, 2004; 128(1): 13 - 23. [Abstract] [Full Text] [PDF]

				V. De Leo, A. la Marca, and F. Petraglia Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome Endocr. Rev., October 1, 2003; 24(5): 633 - 667. [Abstract] [Full Text] [PDF]

				T. M. Plant and G. R. Marshall The Functional Significance of FSH in Spermatogenesis and the Control of Its Secretion in Male Primates Endocr. Rev., December 1, 2001; 22(6): 764 - 786. [Abstract] [Full Text] [PDF]

				F. J. Hayes, N. Pitteloud, S. DeCruz, W. F. Crowley Jr., and P. A. Boepple Importance of Inhibin B in the Regulation of FSH Secretion in the Human Male J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5541 - 5546. [Abstract] [Full Text] [PDF]

				T. Sir-Petermann, L. Devoto, M. Maliqueo, P. Peirano, S.E. Recabarren, and L. Wildt Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: endocrine aspects Hum. Reprod., August 1, 2001; 16(8): 1603 - 1610. [Abstract] [Full Text] [PDF]

				N. Pitteloud, P. A. Boepple, S. DeCruz, S. B. Valkenburgh, W. F. Crowley Jr., and F. J. Hayes The Fertile Eunuch Variant of Idiopathic Hypogonadotropic Hypogonadism: Spontaneous Reversal Associated with a Homozygous Mutation in the Gonadotropin-Releasing Hormone Receptor J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2470 - 2475. [Abstract] [Full Text] [PDF]

				J. E. Hall, H. B. Lavoie, E. E. Marsh, and K. A. Martin Decrease in Gonadotropin-Releasing Hormone (GnRH) Pulse Frequency with Aging in Postmenopausal Women J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1794 - 1800. [Abstract] [Full Text]

				S. B. Seminara, J. E. Hall, A. E. Taylor, W. F. Crowley Jr., and K. A. Martin The Reproductive Endocrine Associates of the Massachusetts General Hospital: Fifteen Years of Integrated Clinical Practice and Investigation J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1912 - 1918. [Full Text]

				F. J. Hayes, D. J. McNicholl, D. Schoenfeld, E. E. Marsh, and J. E. Hall Free {alpha}-Subunit Is Superior to Luteinizing Hormone as a Marker of Gonadotropin-Releasing Hormone Despite Desensitization at Fast Pulse Frequencies J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1028 - 1036. [Abstract] [Full Text]

				F. J. Hayes, A. E. Taylor, K. A. Martin, and J. E. Hall Use of a Gonadotropin-Releasing Hormone Antagonist as a Physiologic Probe in Polycystic Ovary Syndrome: Assessment of Neuroendocrine and Androgen Dynamics J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2343 - 2349. [Abstract] [Full Text]

				D. M. Keenan and J. D. Veldhuis A biomathematical model of time-delayed feedback in the human male hypothalamic-pituitary-Leydig cell axis Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E157 - E176. [Abstract] [Full Text] [PDF]

				C. L. Pastor, M. L. Griffin-Korf, J. A. Aloi, W. S. Evans, and J. C. Marshall Polycystic Ovary Syndrome: Evidence for Reduced Sensitivity of the Gonadotropin-Releasing Hormone Pulse Generator to Inhibition by Estradiol and Progesterone J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 582 - 590. [Abstract] [Full Text]

				T. L. Daniels and S. L. Berga Resistance of Gonadotropin Releasing Hormone Drive to Sex Steroid-Induced Suppression in Hyperandrogenic Anovulation J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4179 - 4183. [Abstract] [Full Text] [PDF]

				A. E. Taylor, B. McCourt, K. A. Martin, E. J. Anderson, J. M. Adams, D. Schoenfeld, and J. E. Hall Determinants of Abnormal Gonadotropin Secretion in Clinically Defined Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2248 - 2256. [Abstract] [Full Text] [PDF]