AGING GH AXIS IN POSTMENOPAUSAL WOMEN

  • Veldhuis, Johannes D (PI)

Project: Research project

Project Details

Description

Prominent age-dependent changes occur in the neuroendocrine control of GH secretion in the human and experimental animals. In some studies, the age-associated decline in pulsatile GH release is correlated best with serum total or free estradiol levels. Thus, there is a major fall-off in GH secretion in the postmenopausal estrogen-deficient state. However, the exact neuroendocrine regulatory mechanisms that drive such clarion estrogen-dependence are not known, but can now be investigated with persuasive clinical neuroendocrine tools. Given the preeminent importance of estrogen withdrawal in postmenopausal hyposomatotropism, our proposed studies will focus on the mechanisms by which postmenopausal estrogen replacement augments pulsatile GH release. In particular, we postulate that one or more of three plausible and testable neuroendocrine mechanisms underlie the strong estrogen-dependent regulation of the human GH axis as exemplified in aging postmenopausal women with or without estrogen-replacement therapy: 1. Estrogen replacement therapy influences GH metabolic clearance, distribution volume, and/or half-life in postmenopausal women. 2. Specific neuroendocrine mechanisms mediated via GH-releasing hormone (GHRH) and/or somatostatin direct pulsatile GH secretion differentially in estrogen-replete versus estrogen-impoverished postmenopausal women: (a) Estrogen sensitizes the GHRH dose-GH secretory response of the pituitary gland. (b)Somatostatin's potency or efficacy in inhibiting GH secretion is attenuated by estrogen. (c) Estrogen enhances L-arginine and GHRH synergism. (d) Estrogen reduces somatostatin release. (e) Estrogen amplifies GHRH's facilitation of post-somatostatin-rebound release of GH. 3. Estrogen replacement in postmenopausal women curtails inhibitory auto- feedback of the hypothalamo-pituitary GH unit otherwise exerted by IGF-I and/or GH. Novel insights into the specific neuroendocrine mechanisms of estrogen action will help explicate the critical physiological coupling between the sex-steroid and GH axes in estrogen-replaced and estrogen-withdrawn postmenopausal women. Such knowledge has significant clinical implications to rational estrogen-replacement strategies in older women with estrogen-deficiency states and physical frailty accompanied by relative hyposomatotropism.
StatusFinished
Effective start/end date3/1/972/28/07

Funding

  • National Institutes of Health
  • National Institutes of Health: $83,108.00
  • National Institutes of Health: $292,000.00
  • National Institutes of Health: $177,120.00
  • National Institutes of Health: $292,000.00
  • National Institutes of Health: $290,260.00
  • National Institutes of Health: $294,632.00
  • National Institutes of Health: $118,880.00
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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