Hu Z, Friberg R D, Barkan A L
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Am J Physiol. 1993 Aug;265(2 Pt 1):E236-42. doi: 10.1152/ajpendo.1993.265.2.E236.
Growth hormone-releasing hormone (GHRH) has been shown in vitro to increase proliferation of pituitary somatotrophs, to increase transcription of the GH gene, to promote accumulation of GH mRNA, and to stimulate GH release. The in vivo involvement of hypothalamic GHRH in regulating GH mRNA content had never been clearly documented. We studied pituitary GH mRNA and GH contents and serum concentrations of GH and insulin-like growth factor I (IGF-I) in rats of both sexes during pubertal growth spurt and investigated the effects of GHRH deficiency (brought about by neonatal administration of monosodium glutamate, MSG) and exogenous GHRH administration on these parameters. In both sexes, GH mRNA content increased three- to fourfold between 4 and 12 wk of life and declined thereafter toward 33 wk of life. This was accompanied by virtually parallel changes in pituitary GH content and in serum IGF-I. Neonatal MSG abolished the pubertal increases in GH mRNA, pituitary GH, and serum IGF-I and severely impaired growth rate. Exogenous GHRH (25 micrograms/kg sc every 8 h for 7 days) given to intact animals between 6 and 7 wk of life significantly augmented pituitary GH mRNA content but was less effective in MSG-treated rats. We conclude that 1) pubertal growth spurt in both sexes is associated with rising pituitary GH mRNA content; 2) GHRH deficiency abolishes the puberty-associated increase in GH synthesis and secretion and attenuates somatic growth rate; and 3) exogenous GHRH augments GH mRNA content. Thus puberty-associated augmentation of GHRH secretion is an important mechanism of somatic growth.
生长激素释放激素（GHRH）在体外已被证明可增加垂体生长激素细胞的增殖、增加生长激素（GH）基因的转录、促进GH信使核糖核酸（mRNA）的积累并刺激GH释放。下丘脑GHRH在体内对调节GH mRNA含量的作用从未得到明确证实。我们研究了青春期生长突增期间雌雄大鼠垂体GH mRNA、GH含量以及血清GH和胰岛素样生长因子I（IGF-I）的浓度，并研究了GHRH缺乏（由新生期注射谷氨酸单钠，即MSG所致）和外源性给予GHRH对这些参数的影响。在雌雄两性中，GH mRNA含量在出生后4至12周增加了三到四倍，此后至33周龄时下降。这伴随着垂体GH含量和血清IGF-I几乎平行的变化。新生期注射MSG消除了青春期GH mRNA、垂体GH和血清IGF-I的增加，并严重损害了生长速度。对6至7周龄的完整动物每8小时皮下注射25微克/千克外源性GHRH，持续7天，可显著增加垂体GH mRNA含量，但对注射MSG的大鼠效果较差。我们得出结论：1）雌雄两性的青春期生长突增与垂体GH mRNA含量增加有关；2）GHRH缺乏消除了青春期相关的GH合成和分泌增加，并减缓了体细胞生长速度；3）外源性GHRH可增加GH mRNA含量。因此，青春期相关的GHRH分泌增加是体细胞生长的重要机制。
