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Testosterone and Oxandrolone, a Nonaromatizable Androgen, Specifically Amplify the Mass and Rate of Growth Hormone (GH) Secreted per Burst without Altering GH Secretory Burst Duration or Frequency or the GH Half-Life^*

Institute Nacional De La Nutrition, Salvador Zubiran (A.U.-A., E.G.-R.) Tlalpan 14000, Mexico;
the Department of Pediatrics (R.M.B., A.D.R., K.L., C.M.C.) and the Interdisciplinary Graduate Biophysics Program (M.L.J., J.D.V.), Division of Endocrinology and Metabolism, Departments of Internal Medicine and Pharmacology, University of Virginia Health Sciences Center Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. Johannes D. Veldhuis, Box 202 Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908.

We investigated the mechanisms by which androgens increase mean circulating GH concentrations in boys. We tested two hypotheses: 1) testosterone increases serum GH concentrations at least in part via an androgen receptor-mediated mechanism, rather than exclusively by way of aromatization to estrogen; 2) androgen augments one or more specific features to GH secretion (secretory burst number, amplitude, and/or duration) and/or prolongs the half-life of GH removal. To examine these hypotheses, prepubertal boys with constitutionally delayed development and/or growth were given injections of testosterone (100 mg monthly; n = 7) or treated with oral oxandrolone, a nonaromatizable androgen (1.25 mg twice daily; n = 5). Pulsatile GH release was studied before and during androgen administration by sampling blood at 20-min intervals for 24 h. The immunoreactive GH time series were subjected to a novel deconvolution technique, which revealed that 1) testosterone and oxandrolone each increased mean (24-h) serum GH concentrations significantly; 2) both androgens augmented the daily endogenous GH secretory rate significantly; 3) increased GH production resulted from a higher mass of GH secreted per burst and a higher maximal rate of GH secretion within each burst; and 4) androgens amplified the magnitude of the nyctohemeral rhythm in the mass (but not frequency) of GH secretory pulses. The observed effects of androgen were specific, since the number and duration of GH secretory bursts and the subjectspecific GH half-life were unaltered by androgen treatment.

We conclude that androgen acting apart from conversion to estrogen is capable of specifically activating the somatotropic axis via distinct neuroendocrine secretory mechanisms.

^* This work was supported in part by NIH Grant RR-00847 to the Clinical Research Center of the University of Virginia; Research Career Development Award 1-KO4-HD-00634 (to J.D.V.); Diabetes and Endocrinology Research Center Grant 5-P60-AM-221251-05; NIH-supported Clinfo Data Reduction Systems; and the Pratt Foundation.

Received March 6, 1989.

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