Sex-steroid hormone modulation of the tripeptidyl control of the human somatotropic axis

Johannes D. Veldhuis, William S. Evans, Stacey M. Anderson, Cyril Y. Bowers

Research output: Contribution to journalReview article

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Abstract

The daunting regulatory complexity of neurotransmitter control of the mammalian somatotropic (GH) axis requires an initially simplified focus on distal interactive peptidyl pathways that converge on somatotrope cells. These signals include GH-releasing hormone (GHRH), GH-releasing peptides (GHRP's, typified by GHRP-2 and ghrelin), and somatostatin (a potent inhibitor). Recent clinical investigations affirm that estrogen significantly regulates the actions of each of GHRH, GHRP-2, and somatostatin. The ensemble effect of this sex steroid is to amplify GH secretory burst mass, enhance nyctohemeral GH rhythmicity, and reduce the orderliness of the GH release process. In particular, regulatory studies document the ability of short-term estrogen repletion in postmenopausal women to (1) augment pituitary responsiveness to a near-maximal GHRP-2 (3 μ/kg) stimulus; (2) increase the potency of recombinant human (rh) GHRH-1,44-amide-driven GH release (monitored during putative somatostatin withdrawal); (3) mute GH's autonegative feedback on GHRP-2 (but not GHRH or exercise)-stimulated GH secretion; and (4) attenuate the dose-dependent inhibitory effects of infused somatostatin. Limited analyses of IGF-I-dependent negative feedback (e.g., imposed by intravenous infusion of the cognate recombinant peptide or, conversely, relieved by GH-receptor blockade-induced depletion of systemic IGF-I availability) point to additional gender/sex-steroid specific control of IGF-I's autorestraint of GH secretion. The extent to which the actions of testosterone mimic the foregoing distinct mechanisms in older men is not yet known.

Original languageEnglish (US)
Pages (from-to)81-111
Number of pages31
JournalJournal of Anti-Aging Medicine
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2002

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ASJC Scopus subject areas

  • Aging

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