Johannes D Veldhuis MD Ali Iranmanesh MD and Daniel Keenan PhD

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Role of Intrinsic GnRH Deficiency in Mediating

Low-Amplitude LH Secretion Contribution of Primary Leydig Cell

Steroidogenic Failure Alterations in Testosterone Feedback Restraint Regulation of the Ensemble Hypothalamo-

Pituitary-Leydig Cell Axis Summary References

The aging process is marked by a relatively subtle short-term decline in reproductive hormone outflow in men. However, the nominal 0.8-1.3% annual fall in systemic bioavailability of testosterone results in a reduction of 30-50% by the sixth through eighth decades of life. Low testosterone concentrations forecast relative sarcopenia, osteopenia, visceral fat accumulation, detectable cognitive impairment, and variable mood depression. Accordingly, the mechanisms driving progressive androgen deprivation are important to understand. To this end, age-associated alterations in three dominant sites of physiological control, namely the hypothalamus, pituitary gland, and testis, are highlighted. The cognate signals are gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and testosterone, which jointly determine androgen availability via feedback and feedforward adaptations. According to this emergent notion, no single gland acts in isolation to maintain homeostasis. An integrative concept is underscored by highlighting how aging-related testosterone depletion is an ensemble outcome of deterioration of interlinked control.

From: Male Hypogonadism: Basic, Clinical, and Therapeutic Principles Edited by: S. J. Winters © Humana Press Inc., Totowa, NJ

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