TY - JOUR
T1 - Sex-steroid hormone modulation of the tripeptidyl control of the human somatotropic axis
AU - Veldhuis, Johannes D.
AU - Evans, William S.
AU - Anderson, Stacey M.
AU - Bowers, Cyril Y.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1089/109454502317629327
DO - 10.1089/109454502317629327
M3 - Review article
AN - SCOPUS:0036090649
SN - 1094-5458
VL - 5
SP - 81
EP - 111
JO - Journal of Anti-Aging Medicine
JF - Journal of Anti-Aging Medicine
IS - 1
ER -