SUPPRESSION OF GROWTH-HORMONE (GH) SECRETION BY A SELECTIVE GH-RELEASING HORMONE (GHRH) ANTAGONIST - DIRECT EVIDENCE FOR INVOLVEMENT OF ENDOGENOUS GHRH IN THE GENERATION OF GH PULSES

被引:83
作者
JAFFE, CA [1 ]
FRIBERG, RD [1 ]
BARKAN, AL [1 ]
机构
[1] DEPT VET AFFAIRS MED CTR, DEPT INTERNAL MED, DIV ENDOCRINOL & METAB, ANN ARBOR, MI 48109 USA
关键词
HYPOTHALAMUS; PITUITARY; HUMAN; PULSATILITY; NEUROENDOCRINE;
D O I
10.1172/JCI116639
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
To study the potential involvement of growth hormone-releasing hormone (GHRH) in the generation of growth hormone (GH) pulses in humans we have used a competitive antagonist to the GHRH receptor, (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2(GHRH-Ant). Six healthy young men were given a bolus injection of GHRH-Ant 400 mug/kg body wt or vehicle at 2200 h and nocturnal GH concentrations were assessed by every 10-min blood sampling until 0800 h. Integrated total and pulsatile GH secretion were suppressed during GHRH-Ant treatment by 40 +/- 6 (SE) % and 75 +/- 5%, respectively. GHRH-Ant suppressed maximum (7.6 +/- 2.2 vs 1.8 +/- 0.5 mug/liter; P < 0.001) and mean (3.3-1.0 vs 1.1 +/- 0.2 mug/liter; P = 0.02) GH pulse amplitudes. There was no change in integrated nonpulsatile GH levels, pulse frequency, or interpulse GH concentration. GHRH-Ant 400 mug/kg also suppressed the GH responses to intravenous boluses of GHRH 0.33 mug / kg given 1, 6, 12, and 24 h later by 95, 81, 59, and 4%, respectively. In five healthy men, the responses to 10-fold larger GHRH boluses (3.3 mug/kg) were suppressed by 82 and 0%, 1 and 6 h after GHRH-Ant 400 mug/kg, respectively. These studies provide the first direct evidence that endogenous GHRH participates in the generation of spontaneous GH pulses in humans.
引用
收藏
页码:695 / 701
页数:7
相关论文
共 61 条
[1]   ALTERATIONS IN THE PULSATILE MODE OF GROWTH-HORMONE RELEASE IN MEN AND WOMEN WITH INSULIN-DEPENDENT DIABETES-MELLITUS [J].
ASPLIN, CM ;
FARIA, ACS ;
CARLSEN, EC ;
VACCARO, VA ;
BARR, RE ;
IRANMANESH, A ;
LEE, MM ;
VELDHUIS, JD ;
EVANS, WS .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1989, 69 (02) :239-245
[2]   INCREASED GROWTH-HORMONE PULSE FREQUENCY IN ACROMEGALY [J].
BARKAN, AL ;
STRED, SE ;
RENO, K ;
MARKOVS, M ;
HOPWOOD, NJ ;
KELCH, RP ;
BEITINS, IZ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1989, 69 (06) :1225-1233
[3]   ON THE INVITRO AND INVIVO ACTIVITY OF A NEW SYNTHETIC HEXAPEPTIDE THAT ACTS ON THE PITUITARY TO SPECIFICALLY RELEASE GROWTH-HORMONE [J].
BOWERS, CY ;
MOMANY, FA ;
REYNOLDS, GA ;
HONG, A .
ENDOCRINOLOGY, 1984, 114 (05) :1537-1545
[4]  
BURRIN JM, 1991, 73RD ANN M END SOC W
[5]  
CHENG K, 1989, ENDOCRINOLOGY, V124, P2791
[6]   PARADOXICAL GROWTH-PROMOTING EFFECTS INDUCED BY PATTERNED INFUSIONS OF SOMATOSTATIN IN FEMALE RATS [J].
CLARK, RG ;
ROBINSON, ICAF .
ENDOCRINOLOGY, 1988, 122 (06) :2675-2682
[7]   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
[8]   CHARACTERISTICS OF THE POST-SOMATOSTATIN REBOUND IN GROWTH-HORMONE SECRETION FROM PERIFUSED SOMATOTROPHS [J].
COWAN, JS ;
MOOR, B ;
CHOW, A ;
KRAICER, J .
ENDOCRINOLOGY, 1983, 113 (03) :1056-1061
[9]  
CRONIN MJ, 1989, ENDOCRINOLOGY, P183
[10]   THE INTERACTION OF HUMAN PANCREATIC GROWTH-HORMONE RELEASING FACTOR-1-44 WITH SOMATOSTATIN INVIVO IN NORMAL MAN [J].
DAVIES, RR ;
TURNER, SJ ;
ORSKOV, H ;
JOHNSTON, DG .
CLINICAL ENDOCRINOLOGY, 1985, 23 (03) :271-276