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Acute Androgen Receptor Blockade Increases Luteinizing Hormone Secretory Activity in Men^*

RANDALL J. URBAN, MICHAEL R. DAVIS, ALAN D. ROGOL, MICHAEL L. JOHNSON and JOHANNES D. VELDHUIS

Division of Endocrinology and Metabolism, Department of Internal Medicine (R.J. V., M.R.D., J.D. V), Charlottesville, Virginia 22908
the Department of Pharmacology (A.D.R., M.L.J.) Charlottesville, Virginia 22908
the Division of Endocrinology and Metabolism, Department of Pediatrics (A.D.R.), University of Virginia School of Medicine Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. Johannes D. Veldhuis, Box 202, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 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 HC1 (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 work was supported in part by NIH Grant RR-00847 (to the University of Virginia Clinical Research Center), Clinical Associate Physician Award 3-MO1-RR-00847-1491 (to R.J.U.), Biomedical Research Support Grant 5-S07-55-05431-26 (to R.J.U.), NIH Grants AM-30302 and GM-28298 (to M.L.J.), Research Career Development Award 1-K04-HD-00634 (to J.D.V.), Diabetes and Research Training Center Grant 5-P60-AM-22125-05, and NIH-supported Clinfo Data Reduction Systems.

Present address: 1653 Springhill Avenue, Mobile, Alabama 36604.

Received May 9, 1988.

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