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This version published online on July 19, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0909
A more recent version of this article appeared on October 1, 2005
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Submitted on April 25, 2005
Accepted on July 12, 2005

Aging in Healthy Men Impairs Recombinant Human LH-Stimulated Testosterone Secretion Monitored Under a Two-Day Intravenous Pulsatile LH Clamp

Peter Y. Liu, Paul Y. Takahashi, Pamela D. Roebuck, Ali Iranmanesh, and Johannes D. Veldhuis*

Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, MN 55905; Department of Internal Medicine, Division of Primary Care Internal Medicine, Mayo Clinic, Rochester, MN 55905

* To whom correspondence should be addressed. E-mail: veldhuis.johannes{at}mayo.edu.

Context. Testosterone (Te) depletion in aging men in principle could reflect deficits in the hypothalamus, pituitary gland or testis. Available pharmacological studies of possible failure of Leydig-cell steroidogenesis remain inconclusive. Objective. To assess Te secretion in older and young men in response to near-physiological LH stimulation. Intervention. Pulsatile iv infusion of recombinant human (rh) LH for 2 days to stimulate Te secretion during suppression of endogenous LH concentrations with a potent selective GnRH-receptor antagonist (ganirelix). Subjects/Context. Healthy older (ages 60-73 y, n = 8) and young (19-30 y, n = 13) men studied in an academic setting. Measures. Pulsatile LH and Te concentrations on the second day of exogenous LH stimulation. Results. Serum ganirelix concentrations and infused LH pulse increments were similar by age. In contrast, older subjects manifested: (a) reduced mean Te concentrations (P = 0.016), Te peak heights (P = 0.014), increments (P = 0.010), summed areas (P < 0.013) and interpeak Te concentrations (P = 0.023); (b) decreased Te/LH concentration ratios (P = 0.002); (c) diminished LH-Te feedforward synchrony (P = 0.020); and (d) a blunted amplitude (P = 0.036) and advanced phase (P = 0.013) of diurnal Te rhythms. Conclusion. A novel regimen of pulsatile LH stimulation for 48 h during GnRH-receptor blockade unmasks deficits in pulsatile, basal, synchronous and nycthemeral Te secretion in healthy older men. These findings do not exclude concomitant defects in GnRH outflow and/or Te negative feedback in the aging male.
Key words: lutropin • androgen • testis • Leydig cell • aging • age • human • male




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