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Journal of Clinical Endocrinology & Metabolism, Vol 80, 3025-3031, Copyright © 1995 by Endocrine Society
ARTICLES |
T Mulligan, A Iranmanesh, S Gheorghiu, M Godschalk and JD Veldhuis
Division of Geriatric Medicine, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA.
The specific mechanisms underlying the relative hypogonadism of aging remain to be elucidated fully. We used frequent venous sampling (every 2.5 min), sensitive and specific LH and testosterone assays, and deconvolution analysis of the endocrine time series to delineate the differences between healthy young (n = 10, age 21-34 yr) and aged (n = 8, age 62-74 yr) men in the nocturnal secretion of LH and testosterone and their half-lives. We found that elderly men vs. young men had more frequent bursts of LH secretion (1.4 vs. 0.9/h, P = 0.003), less testosterone secreted per testosterone secretory burst (9.2 vs. 17.0 nmol/L, P = 0.021), and less testosterone secreted per hour (10.7 vs. 25.0 nmol/L.h, P = 0.05). As the frequency of nocturnal LH secretory bursts increased, the frequency of testosterone bursts decreased (r = - 0.746, P = 0.034). We conclude that healthy aging is associated with diminished nocturnal testosterone production attributable to 1) a decrement in the mass of testosterone released per burst and 2) an inadequate response by the pituitary gland to enhance testosterone production via an accelerated LH secretory pulse frequency. We speculate that this may reflect a partial desensitization of Leydig cells to LH.
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P. Y. Liu, S. M. Pincus, D. M. Keenan, F. Roelfsema, and J. D. Veldhuis Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R440 - R446. [Abstract] [Full Text] [PDF]
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J. D. Veldhuis and A. Iranmanesh Short-Term Aromatase-Enzyme Blockade Unmasks Impaired Feedback Adaptations in Luteinizing Hormone and Testosterone Secretion in Older Men J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 211 - 218. [Abstract] [Full Text] [PDF]
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J. D. Veldhuis and A. Iranmanesh Pulsatile Intravenous Infusion of Recombinant Human Luteinizing Hormone under Acute Gonadotropin-Releasing Hormone Receptor Blockade Reconstitutes Testosterone Secretion in Young Men J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4474 - 4479. [Abstract] [Full Text] [PDF]
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D. M. Keenan and J. D. Veldhuis Divergent gonadotropin-gonadal dose-responsive coupling in healthy young and aging men Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R381 - R389. [Abstract] [Full Text] [PDF]
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K. T. Brill, A. L. Weltman, A. Gentili, J. T. Patrie, D. A. Fryburg, J. B. Hanks, R. J. Urban, and J. D. Veldhuis Single and Combined Effects of Growth Hormone and Testosterone Administration on Measures of Body Composition, Physical Performance, Mood, Sexual Function, Bone Turnover, and Muscle Gene Expression in Healthy Older Men J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5649 - 5657. [Abstract] [Full Text] [PDF]
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T. Mulligan, A. Iranmanesh, and J. D. Veldhuis Pulsatile iv Infusion of Recombinant Human LH in Leuprolide-Suppressed Men Unmasks Impoverished Leydig-Cell Secretory Responsiveness to Midphysiological LH Drive in the Aging Male J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5547 - 5553. [Abstract] [Full Text] [PDF]
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G. Van den Berghe, F. Weekers, R. C. Baxter, P. Wouters, A. Iranmanesh, R. Bouillon, and J. D. Veldhuis Five-Day Pulsatile Gonadotropin-Releasing Hormone Administration Unveils Combined Hypothalamic-Pituitary-Gonadal Defects Underlying Profound Hypoandrogenism in Men with Prolonged Critical Illness J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3217 - 3226. [Abstract] [Full Text] [PDF]
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D. M. Keenan and J. D. Veldhuis Hypothesis testing of the aging male gonadal axis via a biomathematical construct Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2001; 280(6): R1755 - R1771. [Abstract] [Full Text] [PDF]
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R. G. Veldman, M. Frölich, S. M. Pincus, J. D. Veldhuis, and F. Roelfsema Basal, Pulsatile, Entropic, and 24-Hour Rhythmic Features of Secondary Hyperprolactinemia Due to Functional Pituitary Stalk Disconnection Mimic Tumoral (Primary) Hyperprolactinemia J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1562 - 1567. [Abstract] [Full Text]
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J. D. Veldhuis, A. Zwart, T. Mulligan, and A. Iranmanesh Muting of Androgen Negative Feedback Unveils Impoverished Gonadotropin-Releasing Hormone/Luteinizing Hormone Secretory Reactivity in Healthy Older Men J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 529 - 535. [Abstract] [Full Text]
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J. D. Veldhuis, A. Iranmanesh, M. Godschalk, and T. Mulligan Older Men Manifest Multifold Synchrony Disruption of Reproductive Neurohormone Outflow J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1477 - 1486. [Abstract] [Full Text]
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J. D. Veldhuis, Ali Iranmanesh, Thomas Mulligan, and Steven M. Pincus Disruption of the Young-Adult Synchrony between Luteinizing Hormone Release and Oscillations in Follicle-Stimulating Hormone, Prolactin, and Nocturnal Penile Tumescence (NPT) in Healthy Older Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3498 - 3505. [Abstract] [Full Text] [PDF]
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J. D. Veldhuis, A. Iranmanesh, L. M. Demers, and T. Mulligan Joint Basal and Pulsatile Hypersecretory Mechanisms Drive the Monotropic Follicle-Stimulating Hormone (FSH) Elevation in Healthy Older Men: Concurrent Preservation of the Orderliness of the FSH Release Process: A General Clinical Research Center Study J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3506 - 3514. [Abstract] [Full Text] [PDF]
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A. Iranmanesh, T. Mulligan, and J. D. Veldhuis Mechanisms Subserving the Physiological Nocturnal Relative Hypoprolactinemia of Healthy Older Men: Dual Decline in Prolactin Secretory Burst Mass and Basal Release with Preservation of Pulse Duration, Frequency, and Interpulse Interval--A General Clinical Research Center Study J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1083 - 1090. [Abstract] [Full Text]
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D. M. Keenan and J. D. Veldhuis A biomathematical model of time-delayed feedback in the human male hypothalamic-pituitary-Leydig cell axis Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E157 - E176. [Abstract] [Full Text] [PDF]
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M. Bergendahl, J. A. Aloi, A. Iranmanesh, T. M. Mulligan, and J. D. Veldhuis Fasting Suppresses Pulsatile Luteinizing Hormone (LH) Secretion and Enhances Orderliness of LH Release in Young but Not Older Men J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 1967 - 1975. [Abstract] [Full Text]
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T. Mulligan, A. Iranmanesh, M. L. Johnson, M. Straume, and J. D. Veldhuis Aging alters feed-forward and feedback linkages between LH and testosterone in healthy men Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1997; 273(4): R1407 - R1413. [Abstract] [Full Text] [PDF]
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C. Foresta, P. Bordon, M. Rossato, R. Mioni, and J. D. Veldhuis Specific Linkages Among Luteinizing Hormone, Follicle-Stimulating Hormone, and Testosterone Release in the Peripheral Blood and Human Spermatic Vein: Evidence for Both Positive (Feed-Forward) and Negative (Feedback) Within-Axis Regulation J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 3040 - 3046. [Abstract] [Full Text] [PDF]
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A. D. Zwart, A. Iranmanesh, and J. D. Veldhuis Disparate Serum Free Testosterone Concentrations and Degrees of Hypothalamo-Pituitary-Luteinizing Hormone Suppression Are Achieved by Continuous Versus Pulsatile Intravenous Androgen Replacement in Men: A Clinical Experimental Model of Ketoconazole-Induced Reversible Hypoandrogenemia with Controlled Testosterone Add-Back J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2062 - 2069. [Abstract] [Full Text] [PDF]
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J. D. Veldhuis, A. Iranmanesh, E. Samojlik, and R. J. Urban Differential Sex Steroid Negative Feedback Regulation of Pulsatile Follicle-Stimulating Hormone Secretion in Healthy Older Men: Deconvolution Analysis and Steady- State Sex-Steroid Hormone Infusions in Frequently Sampled Healthy Older Individuals J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1248 - 1254. [Abstract] [Full Text] [PDF]
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 S. M. Pincus, T. Mulligan, A. Iranmanesh, S. Gheorghiu, M. Godschalk, and J. D. Veldhuis Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males PNAS, November 26, 1996; 93(24): 14100 - 14105. [Abstract] [Full Text] [PDF]
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