ACTIONS OF TESTOSTERONE ON THE AGING MALE GH AXIS

  • Veldhuis, Johannes D (PI)

Project: Research project

Project Details

Description

Recent patient-oriented investigations establish that progressive hyposomatotropism and hypogonadism consistently accompany healthy aging. The daily secretion of GH and the output of testosterone wane concomitantly in older men, such that by the sixth through eighth decades of life the bioavailability of these hormones is reduced by approximately 50%. The ensuant so-called somatopause and gonadopause encompass an ensemble of signs and symptoms associated with the overall frailty of aging; e.g., limited physical performance and stamina, reduced muscle mass and strength, loss of bone mineral content, increased visceral adiposity, relative dyslipidemia, declining libido and potentia, and variably impaired cognition, sense of well being and quality of life. Based on new and compelling preliminary neuroendocrine data (see Bkgd), here we explore the specific regulatory thesis that the aathoahvsioloclical mechanisms that drive the concomitant somatoaause and aonadoaause are linked causally in the aging male. In particular, we postulate that: I. Short-term restoration of young-adult GH availability by pulsatile i.v. infusions of rh GH will mitigate the age-related decline in LH-driven Leydig-cell testosterone secretion; and, conversely, II. Short-term supplementation with testosterone in older men amplifies GH secretion by way of specific neuroregulatory actions, which explicate its unique twofold stimulation of simultaneous GH and IGF-I production (unlike estrogen action in postmenopausal women); viz.,: (i) muting of GH's autonegative feedback restraint; (ii) enhancement of GHRH feedforward drive; (iii) relief of somatostatinergic inhibition of GH secretion; and/or (iv) facilitation of the endogenous GHRP (GH-releasing peptide)-ligand pathway. The foregoing pivotal clinical postulates will be tested via the combination of a novel interventional strategy (Aim I) and complementary neuroregulatory experiments (Aim II). The outcomes of these clinical mechanistic investigations should clarify further the nature of the pathophysiology subserving joint failure of the somatotropic and gonadal axes in aging men, and thereby begin to illuminate potential targets for preventive strategies desired to limit bihormonal failure and aging- associated frailt in the human.
StatusFinished
Effective start/end date9/15/011/31/17

Funding

  • National Institutes of Health: $333,000.00
  • National Institutes of Health: $332,781.00
  • National Institutes of Health: $314,274.00
  • National Institutes of Health: $328,500.00
  • National Institutes of Health: $328,500.00
  • National Institutes of Health: $5,000.00
  • National Institutes of Health: $377,800.00
  • National Institutes of Health: $317,942.00
  • National Institutes of Health: $328,500.00
  • National Institutes of Health: $366,220.00
  • National Institutes of Health: $5,000.00
  • National Institutes of Health: $302,643.00
  • National Institutes of Health: $377,232.00
  • National Institutes of Health: $320,781.00
  • National Institutes of Health: $317,325.00
  • National Institutes of Health: $391,035.00
  • National Institutes of Health: $360,835.00

ASJC

  • Medicine(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.