Journal of Clinical Endocrinology & Metabolism, Vol 63, 143-150, Copyright © 1986 by Endocrine Society

ARTICLES

Bio- and immunoactive luteinizing hormone responses to low doses of gonadotropin-releasing hormone (GnRH): dose-response curves in GnRH- deficient men

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

Previous investigations of the effects of GnRH on pituitary LH responses in normal men required pharmacological doses of GnRH to avoid the confounding effects of endogenous GnRH secretion and employed nonphysiological dose intervals. To examine the role of GnRH in determining both the qualitative and quantitative nature of physiological LH responses, we studied five GnRH-deficient men in whom pituitary and gonadal function had been normalized with GnRH replacement. Both bio- and immunoactive LH responses were evaluated in these men after a wide range of GnRH doses (7.5-250 ng/kg) administered at a physiological frequency (every 2 h), while gonadal steroid levels were within the normal adult male range. In addition, the amplitude and contour of the immunoactive LH pulses were compared to those of 15 normal men to assure that these experiments achieved physiological pituitary responses. The relationship between bio- and immunoactive LH was compared between patients, between doses as the amount of GnRH was increased, and within pulses of LH. As the dose of GnRH was increased, both bio- and immunoactive LH responses increased in a log-linear fashion when assessed by both amplitude (r = 0.96 for bioactive LH and r = 0.98 for immunoactive LH) and area under the curve (r = 0.99 for bioactive LH and r = 0.97 for immunoactive LH). GnRH doses of 7.5 and 25 ng/kg produced LH responses with amplitudes similar to those in normal men. The relationship between bio- and immunoactive LH between patients and between differing doses of GnRH was analyzed by comparing the slopes of lines fit to individual bioactive vs. immunoactive LH plots after each dose of GnRH in each patient. There was a marked variation in the relationship of bio- to immunoactive LH between patients (P less than 0.005). No change was found in the biopotency of LH as the dose of GnRH was increased (P less than 0.10). Finally, no variation of the bioactivity of LH was evident within individual pulses. We conclude that a log-linear relationship exists between doses of GnRH that produce physiological LH pulses and both bio- and immunoactive LH responses; the bioactivity of secreted LH varies markedly between patients; the relative bioactivity of LH in an individual does not change as the dose of GnRH is increased; and no change in bioactivity of LH responses was demonstrated within pulses of LH.

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]

				Y. L. Pagan, S. S. Srouji, Y. Jimenez, A. Emerson, S. Gill, and J. E. Hall Inverse Relationship between Luteinizing Hormone and Body Mass Index in Polycystic Ovarian Syndrome: Investigation of Hypothalamic and Pituitary Contributions J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1309 - 1316. [Abstract] [Full Text] [PDF]

				M. Bergendah and J. D. Veldhuis Is there a physiological role for gonadotrophin oligosaccharide heterogeneity in humans?: III. Luteinizing hormone heterogeneity: a medical physiologist's perspective Hum. Reprod., June 1, 2001; 16(6): 1058 - 1064. [Abstract] [Full Text] [PDF]

				F. J. Hayes, S. DeCruz, S. B. Seminara, P. A. Boepple, and W. F. Crowley Jr. Differential Regulation of Gonadotropin Secretion by Testosterone in the Human Male: Absence of a Negative Feedback Effect of Testosterone on Follicle-Stimulating Hormone Secretion J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 53 - 58. [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]

				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]