Crawford B A, Dobbie P, Bass J J, Lewitt M S, Baxter R C, Handelsman D J
Department of Obstetrics and Gynaecology, University of Sydney, New South Wales, Australia.
J Endocrinol. 1994 Jun;141(3):393-401. doi: 10.1677/joe.0.1410393.
In many mammalian species, circulating levels of insulin-like growth factor-I (IGF-I) rise during puberty. Previous studies manipulating testosterone levels in rats with normal GH secretion suggested that the pubertal IGF-I rise is regulated by an interaction between GH and sex steroids. Therefore, in a reciprocal study, IGF-I levels were examined during sexual maturation of the GH-deficient dwarf (dw/dw) rat which has a selective genetic deficiency of GH but normal sex steroid levels. Male dw/dw rats were treated with daily injections of recombinant human GH (200 micrograms/100 g body weight) or saline vehicle, from 28 to 70 days of age. Sexual maturation was determined to occur primarily between 42 and 63 days of age based on testis and seminal vesicle growth and plasma testosterone levels. GH treatment had no effect on seminal vesicle weights, plasma testosterone or gonadotrophins. GH administration resulted in a 7% increase in absolute testes weight (P < 0.05), but a 50% increase in body weight (P < 0.0001). These results supported previous findings that the reproductive development of dw/dw rats is essentially normal. Untreated dw/dw rats had no rise in IGF-I levels during sexual maturation. In contrast, treatment with GH produced a marked sustained rise in IGF-I levels (P < 0.0001). LIgand blots demonstrated GH induction of IGF-binding protein-3 (IGFBP-3) and an IGFBP cluster at 32 kDa. The initially high immunoreactive IGFBP-1 levels (> 600 ng/ml) decreased by 49 days of age after which untreated dw/dw rats had significantly higher IGFBP-1 levels than GH-treated dw/dw rats (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
在许多哺乳动物物种中,青春期期间胰岛素样生长因子-I(IGF-I)的循环水平会升高。先前对生长激素分泌正常的大鼠进行睾酮水平调控的研究表明,青春期IGF-I水平的升高受生长激素和性类固醇之间相互作用的调节。因此,在一项反向研究中,对生长激素缺乏的侏儒(dw/dw)大鼠进行了研究,该大鼠具有生长激素的选择性遗传缺陷,但性类固醇水平正常。从28日龄至70日龄,对雄性dw/dw大鼠每日注射重组人生长激素(200微克/100克体重)或生理盐水。根据睾丸和精囊的生长以及血浆睾酮水平,确定性成熟主要发生在42至63日龄之间。生长激素治疗对精囊重量、血浆睾酮或促性腺激素没有影响。给予生长激素使绝对睾丸重量增加了7%(P<0.05),但体重增加了50%(P<0.0001)。这些结果支持了先前的发现,即dw/dw大鼠的生殖发育基本正常。未经治疗的dw/dw大鼠在性成熟期间IGF-I水平没有升高。相比之下,生长激素治疗使IGF-I水平显著持续升高(P<0.0001)。配体印迹显示生长激素诱导了IGF结合蛋白-3(IGFBP-3)以及32 kDa处的一个IGFBP簇。最初较高的免疫反应性IGFBP-1水平(>600纳克/毫升)在49日龄时下降,此后未经治疗的dw/dw大鼠的IGFBP-1水平显著高于生长激素治疗的dw/dw大鼠(P<0.01)。(摘要截断于250字)