Sex-steroid control of the aging somatotropic axis

Johannes D. Veldhuis, Dana Erickson, Ali Iranmanesh, John M. Miles, Cyril Y. Bowers

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations


Fourfold depletion of GH, IGF-I, Te, and E2 in healthy aging adults is accompanied by an increased prevalence of clinical, hormonal, biochemical, and structural features of frailty, disability, and reduced quality of life. In principle, the consequences of diminished GH availability could be overcome by supplementation with rh GH [89-92]. There are no definitive safety data that justify long-term GH administration in healthy older individuals, however. Safety issues are paramount, in as much as injection of high doses of rh GH in certain clinical settings (such as protracted critical illness) exacerbates mortality and in GH-deficient adults may elicit mild acromegalic features [93,94]. Mechanistic understanding of normal GH secretion may allow near-physiologic repletion of GH in selected subgroups of older adults at increased catabolic risk. In consideration of this eventual expectation, Fig. 7 summarizes current understanding of mechanistic deficits in aging individuals. The salient distinctions inferred between aging and young adults are a decrease in feedforward by GHRH and GHRP/ghrelin and an increase in feedback by SS. Te and E2 both augment GH secretion in older individuals. Recent clinical studies have unveiled that Te and E2 exert a complex cascade of specific effects on signaling by GHRH and ghrelin/GHRP (stimulatory), somatostatin (inhibitory), and GH and IGF-I (feedback) (see Table 2). The conjoined outcome is amplification of pulsatile GH secretion. Further clinical studies are needed to determine how Te and E2 drive multi-signal-dependent GH production and modulate organ-specific actions of GH, IGF-I, and IGFBPs in aging individuals.

Original languageEnglish (US)
Pages (from-to)877-893
Number of pages17
JournalEndocrinology and Metabolism Clinics of North America
Issue number4
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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