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Am J Physiol Regul Integr Comp Physiol 289: R721-R728, 2005. First published May 12, 2005; doi:10.1152/ajpregu.00138.2005
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Age-specific changes in the regulation of LH-dependent testosterone secretion: assessing responsiveness to varying endogenous gonadotropin output in normal men

Peter Y. Liu,1 Paul Y. Takahashi,2 Pamela D. Roebuck,1 Ali Iranmanesh,3 and Johannes D. Veldhuis1

1Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center and 2Division of Primary Care Internal Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; and 3Endocrine Service, Research and Development, Salem Veterans Affairs Medical Center, Salem, Massachusetts

Submitted 24 February 2005 ; accepted in final form 6 May 2005

Pulsatile and thus total testosterone (Te) secretion declines in older men, albeit for unknown reasons. Analytical models forecast that aging may reduce the capability of endogenous luteinizing hormone (LH) pulses to stimulate Leydig cell steroidogenesis. This notion has been difficult to test experimentally. The present study used graded doses of a selective gonadotropin releasing hormone (GnRH)-receptor antagonist to yield four distinct strata of pulsatile LH release in each of 18 healthy men ages 23–72 yr. Deconvolution analysis was applied to frequently sampled LH and Te concentration time series to quantitate pulsatile Te secretion over a 16-h interval. Log-linear regression was used to relate pulsatile LH secretion to attendant pulsatile Te secretion (LH-Te drive) across the four stepwise interventions in each subject. Linear regression of the 18 individual estimates of LH-Te feedforward dose-response slopes on age disclosed a strongly negative relationship (r = –0.721, P < 0.001). Accordingly, the present data support the thesis that aging in healthy men attenuates amplitude-dependent LH drive of burst-like Te secretion. The experimental strategy of graded suppression of neuroglandular outflow may have utility in estimating dose-response adaptations in other endocrine systems.

gonadotropin releasing hormone; luteinizing hormone; aging; male; androgen; secretion


Address for reprint requests and other correspondence: J. D. Velduis, Endocrine Research Unit, Dept. of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, MN 55905 (e-mail: veldhuis.johannes{at}mayo.edu)






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