TY - JOUR
T1 - Sex-Steroid Modulation of Growth Hormone (GH) Secretory Control
T2 - Three-Peptide Ensemble Regulation under Dual Feedback Restraint by GH and IGF-I
AU - Veldhuis, Johannes D.
AU - Bowers, Cyril Y.
N1 - Funding Information:
The authors thank Jean Plote for excellent editorial support. This work was supported in part by the National Center for Research Resources via General Clinical Research Center grant RR00585 to the Mayo Clinic and Foundation and NIH ROI AG 14799-05 and AG 19695-02.
PY - 2003/10
Y1 - 2003/10
N2 - Technical, genetic, and clinical developments have unveiled a burgeoning array of novel effectors of GH secretion. The present appraisal of central neuroregulatory components of the somatotropic axis highlights a simplifying concept of ensemble control by the final common peptides, GH-releasing hormone (GHRH), GH-releasing peptide(s) (CHRP, ghrelin), and somatostatin. These potent signals act individually, antagonistically, and synergistically to direct pulsatile GH secretion. GHRH, GHRP/ghrelin, and somatostatin further adapt to autonegative feedback by GH and IGF-I. Estradiol modulates the impact of each of the primary peptidyl inputs; viz.: (i) enhances submaximally effective feedforward by discrete pulses of (injected) recombinant human GHRH-1,44-amide (as defined by increased agonistic potency and pituitary sensitivity); (ii) potentiates the submaximally stimulatory effects of GHRP-2, a hexapeptidyl mimetic of ghrelin; (iii) blunts dose-dependent inhibition of fasting GH secretion by somatostatin-14; and (iv) relieves rhGH-enforced negative feedback on GHRP-2 (but not on basal, exercise, or GHRH)-stimulated GH secretion. The foregoing estrogenic activities collectively augment GH secretory burst mass by amplifying feedforward (via both GHRH and GHRP) and attenuating feedback (imposed by somatotatin and GH). Whether testosterone fully mimics the foregoing mechanistic actions of estradiol is not known. In conclusion, the present conceptual platform of tripeptide-directed feedforward and GH/IGF-I-mediated feedback should aid in unraveling some of the complex regulatory dynamics targeted by sex-steroid hormones.
AB - Technical, genetic, and clinical developments have unveiled a burgeoning array of novel effectors of GH secretion. The present appraisal of central neuroregulatory components of the somatotropic axis highlights a simplifying concept of ensemble control by the final common peptides, GH-releasing hormone (GHRH), GH-releasing peptide(s) (CHRP, ghrelin), and somatostatin. These potent signals act individually, antagonistically, and synergistically to direct pulsatile GH secretion. GHRH, GHRP/ghrelin, and somatostatin further adapt to autonegative feedback by GH and IGF-I. Estradiol modulates the impact of each of the primary peptidyl inputs; viz.: (i) enhances submaximally effective feedforward by discrete pulses of (injected) recombinant human GHRH-1,44-amide (as defined by increased agonistic potency and pituitary sensitivity); (ii) potentiates the submaximally stimulatory effects of GHRP-2, a hexapeptidyl mimetic of ghrelin; (iii) blunts dose-dependent inhibition of fasting GH secretion by somatostatin-14; and (iv) relieves rhGH-enforced negative feedback on GHRP-2 (but not on basal, exercise, or GHRH)-stimulated GH secretion. The foregoing estrogenic activities collectively augment GH secretory burst mass by amplifying feedforward (via both GHRH and GHRP) and attenuating feedback (imposed by somatotatin and GH). Whether testosterone fully mimics the foregoing mechanistic actions of estradiol is not known. In conclusion, the present conceptual platform of tripeptide-directed feedforward and GH/IGF-I-mediated feedback should aid in unraveling some of the complex regulatory dynamics targeted by sex-steroid hormones.
KW - Aging
KW - Feedback
KW - GHRH
KW - GHRP
KW - IGF-I
KW - Puberty
KW - Sex steroids
KW - Somatostatin
KW - Somatotropin
UR - http://www.scopus.com/inward/record.url?scp=0242576758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242576758&partnerID=8YFLogxK
U2 - 10.1385/ENDO:22:1:25
DO - 10.1385/ENDO:22:1:25
M3 - Review article
C2 - 14610296
AN - SCOPUS:0242576758
SN - 1355-008X
VL - 22
SP - 25
EP - 39
JO - Endocrine
JF - Endocrine
IS - 1
ER -