Journal of Clinical Endocrinology & Metabolism, Vol 74, 96-102, Copyright © 1992 by Endocrine Society

ARTICLES

Divergent effects of short term glucocorticoid excess on the gonadotropic and somatotropic axes in normal men

JD Veldhuis, G Lizarralde and A Iranmanesh
Department of Internal Medicine, National Science Foundation Science Center in Biological Timing, University of Virginia Health Sciences Center, Charlottesville 22908.

We investigated the effects of short term glucocorticoid excess on the gonadotropic and somatotropic axes in healthy men. Subjects (n = 5) underwent blood sampling at 10-min intervals for 6 h before and on days 2, 5, and 8 of glucocorticoid treatment, and for 24 h (n = 6) to examine pulsatile LH and GH release before and during dexamethasone administration (1.5 mg orally twice daily for 1 week). In the time- course study, we found significant decreases on day 8 in serum concentrations of estradiol (from 144 +/- 18 to 99 +/- 18 pmol/L), free testosterone (from 105 +/- 10 to 87 +/- 10 pmol/L), and dehydroepiandrosterone sulfate (from 6.0 +/- 1.6 to 1.7 +/- 0.3 mumol/L; P less than 0.05). Mean serum LH concentrations did not change (baseline, 5.3 +/- 1.2 IU/L; glucocorticoid, 4.2 +/- 0.61 IU/L). The mean plasma somatomedin-C concentration rose from 0.74 +/- 0.08 to 2.0 +/- 0.35 U/mL (P less than 0.05), and the mean serum GH concentration increased from 1.2 +/- 0.90 micrograms/L (basal) to 4.2 +/- 1.5 micrograms/L (day 8 of dexamethasone; P less than 0.01). Deconvolution analysis of 24-h serum GH and LH concentration profiles revealed that the half-life of endogenous GH and the duration and amplitude (maximal rate of secretion) of computer-resolved GH secretory bursts were not influenced significantly by dexamethasone. The mass of GH secreted per burst rose 1.6-fold. Glucocorticoid treatment also increased detectable GH secretory burst frequency from 12 +/- 1.6 to 18 +/- 1.6 episodes/24 h, decreased the GH interburst interval from 127 +/- 23 to 79 +/- 5 min, and increased the daily GH secretion rate from 41 +/- 11 to 101 +/- 11 micrograms/L.day. These effects on the somatotropic axis were specific, since the half-life of LH; LH secretory burst frequency, amplitude, mass, and duration; and the total daily LH production rate (and LH secretion in response to exogenous GnRH) were not altered by dexamethasone administration. We conclude that short term moderate glucocorticoid excess augments pulsatile GH secretion without influencing the episodic release of LH in normal men.

This article has been cited by other articles:

				P. Y. Liu, P. Y. Takahashi, P. D. Roebuck, J. N. Bailey, D. M. Keenan, and J. D. Veldhuis Testosterone's Short-Term Positive Effect on Luteinizing-Hormone Secretory-Burst Mass and Its Negative Effect on Secretory-Burst Frequency Are Attenuated in Middle-Aged Men J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 3978 - 3986. [Abstract] [Full Text] [PDF]

				P. Y. Liu, P. Y. Takahashi, P. D. Roebuck, and J. D. Veldhuis Age or Factors Associated with Aging Attenuate Testosterone's Concentration-Dependent Enhancement of the Regularity of Luteinizing Hormone Secretion in Healthy Men J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4077 - 4084. [Abstract] [Full Text] [PDF]

				T S. Kavitha, C Parthasarathy, R Sivakumar, R Badrinarayanan, and K Balasubramanian Effects of excess corticosterone on NADPH generating enzymes and glucose oxidation in Leydig cells of adult rats Human and Experimental Toxicology, March 1, 2006; 25(3): 119 - 125. [Abstract] [PDF]

				W. de Ronde, A. Hofman, H. A P Pols, and F. H de Jong A direct approach to the estimation of the origin of oestrogens and androgens in elderly men by comparison with hormone levels in postmenopausal women Eur. J. Endocrinol., February 1, 2005; 152(2): 261 - 268. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, A. Iranmanesh, and T. Mulligan Age and Testosterone Feedback Jointly Control the Dose-Dependent Actions of Gonadotropin-Releasing Hormone in Healthy Men J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 302 - 309. [Abstract] [Full Text] [PDF]

				L. Gennari, R. Nuti, and J. P. Bilezikian Aromatase Activity and Bone Homeostasis in Men J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 5898 - 5907. [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]

				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]

				J. A. Gusenoff, S. M. Harman, J. D. Veldhuis, J. J. Jayme, C. St. Clair, T. Munzer, C. Christmas, K. G. O'Connor, T. E. Stevens, M. F. Bellantoni, et al. Cortisol and GH secretory dynamics, and their interrelationships, in healthy aged women and men Am J Physiol Endocrinol Metab, April 1, 2001; 280(4): E616 - E625. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, A. Zwart, T. Mulligan, and A. Iranmanesh Muting of Androgen Negative Feedback Unveils Impoverished Gonadotropin-Releasing Hormone/Luteinizing Hormone Secretory Reactivity in Healthy Older Men J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 529 - 535. [Abstract] [Full Text]

				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]

				C.A. Daley, H. Sakurai, B.M. Adams, and T.E. Adams Effect of Stress-Like Concentrations of Cortisol on Gonadotroph Function in Orchidectomized Sheep Biol Reprod, January 1, 1999; 60(1): 158 - 163. [Abstract] [Full Text]

				A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human Endocr. Rev., December 1, 1998; 19(6): 717 - 797. [Abstract] [Full Text]

				J. Lado-Abeal, J. Rodriguez-Arnao, J. D. C. Newell-Price, L. A. Perry, A. B. Grossman, G. M. Besser, and P. J. Trainer Menstrual Abnormalities in Women with Cushing's Disease Are Correlated with Hypercortisolemia Rather Than Raised Circulating Androgen Levels J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3083 - 3088. [Abstract] [Full Text]

				A. Leal-Cerro, L. M. Jimenez, R. Astorga, I. Fernandez-Lopez, C. Dieguez, and F. F. Casanueva Acute Pharmacological Reduction of Plasma Free Fatty Acids Enhances the Growth Hormone (GH)-Releasing Hormone-Mediated GH Secretion in Patients with Cushing's Syndrome J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 3165 - 3168. [Abstract] [Full Text] [PDF]

				A. D. Zwart, A. Iranmanesh, and J. D. Veldhuis Disparate Serum Free Testosterone Concentrations and Degrees of Hypothalamo-Pituitary-Luteinizing Hormone Suppression Are Achieved by Continuous Versus Pulsatile Intravenous Androgen Replacement in Men: A Clinical Experimental Model of Ketoconazole-Induced Reversible Hypoandrogenemia with Controlled Testosterone Add-Back J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2062 - 2069. [Abstract] [Full Text] [PDF]