Journal of Clinical Endocrinology & Metabolism, Vol 67, 1149-1155, Copyright © 1988 by Endocrine Society

ARTICLES

Acute androgen receptor blockade increases luteinizing hormone secretory activity in men

RJ Urban, MR Davis, AD Rogol, ML Johnson and JD Veldhuis
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.

To investigate the nature of androgen feedback mechanisms in normal men, we studied the hypothalamo-pituitary responses to administration of a potent, highly selective nonsteroidal androgen receptor antagonist, flutamide HCl (1 g/day, orally, for 3 days). The impact of reversible blockade of endogenous androgen action was assessed in 11 normal men by analyzing quantitative alterations in specific pulsatile properties of LH secretion basally (hypothalamic regulation) and after 2 (n = 6) consecutive iv pulses of exogenous GnRH (pituitary responsiveness). Androgen blockade resulted in significant increases in 1) 12-h mean and integrated serum immunoactive LH concentrations (P = 0.01), 2) LH pulse frequency (P = 0.01), and 3) mean interpulse (valley) serum LH concentrations (P = 0.02) and maximal LH peak heights (P = 0.01). Additionally, there were significant decreases in LH interpulse interval (P = 0.02), LH peak duration (P = 0.02), and interpeak valley duration (P = 0.02). The augmented LH pulsatility reflected enhanced hypothalamic activity, since 1) pituitary secretory responses to exogenous GnRH pulses were not altered, and 2) multiple parameter deconvolution disclosed an increased number of computer- resolved LH secretory bursts generated per 12 h, with no changes in the apparent half-duration of LH secretory impulses or the calculated mass of LH released per secretory burst. We conclude that endogenous androgens act selectively to modulate the number of spontaneous LH secretory bursts in man.

This article has been cited by other articles:

				S. T. Page, J. K. Amory, and W. J. Bremner Advances in Male Contraception Endocr. Rev., June 1, 2008; 29(4): 465 - 493. [Abstract] [Full Text] [PDF]

				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]

				P. Y. Liu, A. Iranmanesh, D. M. Keenan, S. M. Pincus, and J. D. Veldhuis A noninvasive measure of negative-feedback strength, approximate entropy, unmasks strong diurnal variations in the regularity of LH secretion Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1409 - E1415. [Abstract] [Full Text] [PDF]

				D. M. Keenan, P. Y. Takahashi, P. Y. Liu, P. D. Roebuck, A. X. Nehra, A. Iranmanesh, and J. D. Veldhuis An Ensemble Model of the Male Gonadal Axis: Illustrative Application in Aging Men Endocrinology, June 1, 2006; 147(6): 2817 - 2828. [Abstract] [Full Text] [PDF]

				J. Pielecka and S. M. Moenter Effect of Steroid Milieu on Gonadotropin-Releasing Hormone-1 Neuron Firing Pattern and Luteinizing Hormone Levels in Male Mice Biol Reprod, May 1, 2006; 74(5): 931 - 937. [Abstract] [Full Text] [PDF]

				P. Y. Liu, S. M. Pincus, P. Y. Takahashi, P. D. Roebuck, A. Iranmanesh, D. M. Keenan, and J. D. Veldhuis Aging attenuates both the regularity and joint synchrony of LH and testosterone secretion in normal men: analyses via a model of graded GnRH receptor blockade Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E34 - E41. [Abstract] [Full Text] [PDF]

				A. Iranmanesh and J. D. Veldhuis Combined Inhibition of Types I and II 5 {alpha}-Reductase Selectively Augments the Basal (Nonpulsatile) Mode of Testosterone Secretion in Young Men J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4232 - 4237. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, A. D. Rogol, J. C. Lovejoy, M. Sheffield-Moore, N. Mauras, and C. Y. Bowers Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocr. Rev., February 1, 2005; 26(1): 114 - 146. [Abstract] [Full Text] [PDF]

				R. A. Anderson and D. T. Baird Male Contraception Endocr. Rev., December 1, 2002; 23(6): 735 - 762. [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]

				D. M. Keenan and J. D. Veldhuis Hypothesis testing of the aging male gonadal axis via a biomathematical construct Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1755 - R1771. [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]

				J. D. Veldhuis, S. M. Pincus, R. Mitamura, K. Yano, N. Suzuki, Y. Ito, Y. Makita, and A. Okuno Developmentally Delimited Emergence of More Orderly Luteinizing Hormone and Testosterone Secretion during Late Prepuberty in Boys J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 80 - 89. [Abstract] [Full Text]

				C. Castro-Fernández, A. Olivares, D. Söderlund, J. C. López-Alvarenga, E. Zambrano, J. D. Veldhuis, A. Ulloa-Aguirre, and J. P. Méndez A Preponderance of Circulating Basic Isoforms Is Associated with Decreased Plasma Half-Life and Biological to Immunological Ratio of Gonadotropin-Releasing Hormone-Releasable Luteinizing Hormone in Obese Men J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4603 - 4610. [Abstract] [Full Text]

				J. D. Veldhuis, A. Iranmanesh, L. M. Demers, and T. Mulligan Joint Basal and Pulsatile Hypersecretory Mechanisms Drive the Monotropic Follicle-Stimulating Hormone (FSH) Elevation in Healthy Older Men: Concurrent Preservation of the Orderliness of the FSH Release Process: A General Clinical Research Center Study J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3506 - 3514. [Abstract] [Full Text] [PDF]

				J. Lindzey, W. C. Wetsel, J. F. Couse, T. Stoker, R. Cooper, and K. S. Korach Effects of Castration and Chronic Steroid Treatments on Hypothalamic Gonadotropin-Releasing Hormone Content and Pituitary Gonadotropins in Male Wild-Type and Estrogen Receptor-{alpha} Knockout Mice Endocrinology, October 1, 1998; 139(10): 4092 - 4101. [Abstract] [Full Text] [PDF]

				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]

				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]