Insulin-like growth factor I of peripheral origin acts centrally to accelerate the initiation of female puberty.

Insulin-like growth factor I of peripheral origin acts centrally to accelerate the initiation of female puberty.
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DOI:
10.1210/endo.137.9.8756538
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发表时间:
1996-09
期刊:
影响因子:
4.8
通讯作者:
J. Hiney;V. Srivastava;Christopher L. Nyberg;S. Ojeda;W. Dees
J. Hiney;V. Srivastava;Christopher L. Nyberg;S. Ojeda;W. Dees
中科院分区:
医学2区
文献类型:
--
作者:
J. Hiney;V. Srivastava;Christopher L. Nyberg;S. Ojeda;W. Dees

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在包括人类在内的几个物种中,循环胰岛素样生长因子I(IGF-I)水平在青春期开始时增加,表明这种肽有助于达到性成熟。由于IGF-I elabetes LHRH释放从正中隆起(ME)的未成熟的雌性大鼠在体外,我们假设,它可能代表一个外围信号怀疑身体发育的LHRH释放系统在青春期。我们现在提出的证据支持这一概念。IGF-I信使RNA(mRNA)水平的核糖核酸酶保护试验的定量显示,IGF-I基因的表达没有改变,在内侧基底下丘脑或视前区的雌性大鼠在青春期发育。与此相反,IGF-Ia和IGF-Ib mRNA的含量,IGF-I基因的两种选择性剪接形式,在青春期的早期发情前期肝脏显着增加。这一变化之后,血清IGF-I水平升高,在晚前期的青春期沿着伴随着增加血清促性腺激素水平。血清IGF-I水平的动情前期变化伴随着ME中IGF-I受体(IGF-IR)mRNA的选择性增加。小剂量IGF-I(2-200 ng),脑室注射,有效地诱导幼年和青春期前后雌性大鼠LH的释放,这种增加可通过预先免疫中和LHRH作用来阻止。重要的是,脑室内注射IGF-I(20 ng),每天下午给药两次给未成熟的动物,显着提前青春期。因此,这些结果表明,IGF-I的外周来源有助于启动女性青春期的刺激LHRH释放从下丘脑,一种效果,似乎是放大的增加合成的IGF-I受体在ME在第一次发情前期。
In several species, including humans, circulating insulin-like growth factor I (IGF-I) levels increase during the onset of puberty, suggesting that this peptide contributes to attaining sexual maturity. Because IGF-I elicits LHRH release from the median eminence (ME) of immature female rats in vitro, we hypothesized that it may represent one of the peripheral signals suspected to link somatic development to the LHRH-releasing system at puberty. We now present evidence in support of this concept. Quantitation of IGF-I messenger RNA (mRNA) levels by ribonuclease protection assay revealed that expression of the IGF-I gene did not change in the medial basal hypothalamus or preoptic area of female rats during peripubertal development. In contrast, the contents of both IGF-Ia and IGF-Ib mRNA, the two alternatively spliced forms of the IGF-I gene, increased significantly in the liver during the early proestrous phase of puberty. This change was followed by an elevation in serum IGF-I levels during the late proestrous phase of puberty along with a concomitant increase is serum gonadotropin levels. The proestrous change in serum IGF-I levels was accompanied by a selective increase in IGF-I receptor (IGF-IR) mRNA in the ME. Small doses of IGF-I (2-200 ng), administered intraventricularly, effectively induced LH release in both juvenile and peripubertal female rats, an increase prevented by prior immunoneutralization of LHRH actions. Importantly, intraventricular injections of IGF-I (20 ng), administered twice daily in the afternoon to immature animals, significantly advanced puberty. Thus, these results suggest that IGF-I of peripheral origin contributes to the initiation of female puberty by stimulating LHRH release from the hypothalamus, an effect that appears to be amplified by the increased synthesis of IGF-I receptors in the ME during first proestrus.