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This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/E775    most recent 00410.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Veldhuis, J. D. Articles by Iranmanesh, A. Search for Related Content PubMed PubMed Citation Articles by Veldhuis, J. D. Articles by Iranmanesh, A.

Age diminishes the testicular steroidogenic response to repeated intravenous pulses of recombinant human LH during acute GnRH-receptor blockade in healthy men

¹Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota; ²Departments of Bioethics and Statistics, University of Virginia, Charlottesville; and ³Endocrine Service, Research and Development, Salem Veterans Affairs Medical Center, Salem, Virginia

Submitted 31 August 2004 ; accepted in final form 17 November 2004

Testosterone (Te) concentrations fall gradually in healthy aging men. Postulated mechanisms include relative failure of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and/or gonadal Te secretion. Available methods to test Leydig cell Te production include pharmacological stimulation with human chorionic gonadotropin (hCG). We reasoned that physiological lutropic signaling could be mimicked by pulsatile infusion of recombinant human (rh) LH during acute suppression of LH secretion. To this end, we studied eight young (ages 19–30 yr) and seven older (ages 61–73 yr) men in an experimental paradigm comprising 1) inhibition of overnight LH secretion with a potent selective GnRH-receptor antagonist (ganirelix, 2 mg sc), 2) intravenous infusion of consecutive pulses of rh LH (50 IU every 2 h), and 3) chemiluminometric assay of LH and Te concentrations sampled every 10 min for 26 h. Statistical analyses revealed that 1) ganirelix suppressed LH and Te equally (> 75% median inhibition) in young and older men, 2) infused LH pulse profiles did not differ by age, and 3) successive intravenous pulses of rh LH increased concentrations of free Te (ng/dl) to 4.6 ± 0.38 (young) and 2.1 ± 0.14 (older; P < 0.001) and bioavailable Te (ng/dl) to 337 ± 20 (young) and 209 ± 16 (older; P = 0.002). Thus controlled pulsatile rh LH drive that emulates physiological LH pulses unmasks significant impairment of short-term Leydig cell steroidogenesis in aging men. Whether more prolonged pulsatile LH stimulation would normalize this inferred defect is unknown.

luteinizing hormone; Leydig cell; aging; male; human

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