Recovery of growth hormone release from suppression by exogenous insulin-like growth factor I (IGF-I): Evidence for a suppressive action of free rather than bound IGF-I

被引:60
作者
Chapman, IM
Hartman, ML
Pieper, KS
Skiles, EH
Pezzoli, SS
Hintz, RL
Thorner, MO
机构
[1] Univ Virginia, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, Charlottesville, VA 22908 USA
[2] Univ Virginia, Hlth Sci Ctr, Dept Hlth Evaluat Sci, Div Biostat & Endocrinol, Charlottesville, VA 22908 USA
[3] Stanford Univ, Med Ctr, Dept Pediat, Stanford, CA 94305 USA
关键词
D O I
10.1210/jc.83.8.2836
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To determine the time course of recovery of GH release from insulin-like growth factor I(IGF-I) suppression, 11 healthy adults (18-29 yr) received, in randomized order, 4-h iv infusions of recombinant human IGF-I (rhIGF-I; 3 mu g/kg.h) or saline (control) from 25.5-29.5 h of a 47.5-h fast. Serum GH was maximally suppressed within 2 h and remained suppressed for 2 h after the rhIGF-I infusion; during this 4-h period, GH concentrations mere approximately 25% of control day levels [median (interquartile range), 1.2 (0.4-4.0) vs. 4.8 (2.8-7.9) mu g/L; P < 0.05]. A rebound increase in GH concentrations occurred 5-7 h after the end of rhIGF-I infusion [7.6 (4.6-11.7) vs. 4.3 (2.5-6.0) mu g/L; P < 0.05]. Thereafter, serum GH concentrations were similar on both days. Total IGF-I concentrations peaked at the end of the rhIGF-I infusion (432 +/- 43 vs. 263 +/- 44 mu g/L; P < 0.0001) and remained elevated 18 h after the rhIGF-I infusion (360 +/- 36 vs. 202 +/- 23 mu g/L; P = 0.001). Free IGF-I concentrations were approximately 140% above control day values at the end of the infusion (2.1 +/- 0.4 vs. 0.88 +/- 0.3 mu g/L; P = 0.001), but declined to baseline within 2 h after the infusion. The close temporal association between the resolution of GH suppression and the fall of free IGF-I concentrations, and the lack of any association with total IGF-I concentrations suggest that unbound (free), not protein-bound, IGF-I is the major IGF-I component responsible for this suppression. The rebound increase in GH concentrations after the end of rhIGF-I infusion is consistent with cessation of an inhibitory effect of free IGF-I on GH release.
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收藏
页码:2836 / 2842
页数:7
相关论文
共 44 条
[1]   INSULIN-LIKE GROWTH FACTOR-I MODULATES HYPOTHALAMIC SOMATOSTATIN THROUGH A GROWTH-HORMONE RELEASING-FACTOR INCREASED SOMATOSTATIN RELEASE AND MESSENGER-RIBONUCLEIC-ACID LEVELS [J].
AGUILA, MC ;
BOGGARAM, V ;
MCCANN, SM .
BRAIN RESEARCH, 1993, 625 (02) :213-218
[2]   SOMATOMEDIN-C MEDIATES GROWTH-HORMONE NEGATIVE FEEDBACK BY EFFECTS ON BOTH THE HYPOTHALAMUS AND THE PITUITARY [J].
BERELOWITZ, M ;
SZABO, M ;
FROHMAN, LA ;
FIRESTONE, S ;
CHU, L ;
HINTZ, RL .
SCIENCE, 1981, 212 (4500) :1279-1281
[3]   NEGATIVE FEEDBACK-REGULATION OF PULSATILE GROWTH-HORMONE SECRETION BY INSULIN-LIKE GROWTH-FACTOR-I - INVOLVEMENT OF HYPOTHALAMIC SOMATOSTATIN [J].
BERMANN, M ;
JAFFE, CA ;
TSAI, W ;
DEMOTTFRIBERG, R ;
BARKAN, AL .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (01) :138-145
[4]   Somatostatin withdrawal as generator of pulsatile GH release in the dog: A possible tool to evaluate the endogenous GHRH tone? [J].
Cella, SG ;
Luceri, M ;
Cattaneo, L ;
Torsello, A ;
Muller, EE .
NEUROENDOCRINOLOGY, 1996, 63 (06) :481-488
[5]   Effect of aging on the sensitivity of growth hormone secretion to insulin-like growth factor-I negative feedback [J].
Chapman, IM ;
Hartman, ML ;
Pezzoli, SS ;
Harrell, FE ;
Hintz, RL ;
Alberti, KGMM ;
Thorner, MO .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (09) :2996-3004
[6]   ENHANCED SENSITIVITY GROWTH-HORMONE (GH) CHEMILUMINESCENCE ASSAY REVEALS LOWER POSTGLUCOSE NADIR GH CONCENTRATIONS IN MEN THAN WOMEN [J].
CHAPMAN, IM ;
HARTMAN, ML ;
STRAUME, M ;
JOHNSON, ML ;
VELDHUIS, JD ;
THORNER, MO .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1994, 78 (06) :1312-1319
[7]   THE EFFECTS OF RECOMBINANT INSULIN-LIKE GROWTH FACTOR-I ADMINISTRATION ON GROWTH-HORMONE LEVELS AND INSULIN REQUIREMENTS IN ADOLESCENTS WITH TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS [J].
CHEETHAM, TD ;
JONES, J ;
TAYLOR, AM ;
HOLLY, J ;
MATTHEWS, DR ;
DUNGER, DB .
DIABETOLOGIA, 1993, 36 (07) :678-681
[8]   THE REBOUND RELEASE OF GROWTH-HORMONE (GH) FOLLOWING SOMATOSTATIN INFUSION IN RATS INVOLVES HYPOTHALAMIC GH-RELEASING FACTOR RELEASE [J].
CLARK, RG ;
CARLSSON, LMS ;
RAFFERTY, B ;
ROBINSON, ICAF .
JOURNAL OF ENDOCRINOLOGY, 1988, 119 (03) :397-404
[9]  
CLARK RG, 1993, GROWTH REGULAT, V3, P50
[10]   INDUCTION OF IMMUNOREACTIVE SOMATOMEDIN-C IN HUMAN-SERUM BY GROWTH-HORMONE - DOSE-RESPONSE RELATIONSHIPS AND EFFECT ON CHROMATOGRAPHIC PROFILES [J].
COPELAND, KC ;
UNDERWOOD, LE ;
VANWYK, JJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1980, 50 (04) :690-697