Gender-dependent role of endogenous somatostatin in regulating growth hormone-axis function in mice
Gender-dependent role of endogenous somatostatin in regulating growth hormone-axis function in mice
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DOI：
10.1210/en.2007-0946
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发表时间：
2007-12-01
期刊：
影响因子：
4.8
通讯作者：
Kineman, Rhonda D.
中科院分区：
文献类型：
--
作者：
Luque, Raul M.;Kineman, Rhonda D.
此前曾报道，与 Sst+/+ 小鼠相比，雄性和雌性生长抑素 (SST) 敲除小鼠 (Sst-/-) 释放更多 GH，因为 GH 分泌囊泡释放增强。内源性 SST 还可以通过直接抑制 GHRH 刺激的 GH 基因表达和/或通过调节下丘脑 GHRH 输入来调节 GH 分泌。为了开始探索这些可能性并更多地了解 SST 在调节 GH 轴功能中的性别依赖性作用，对雄性和雌性 Sst-/- 和 Sst-/- 小鼠的 GH 轴的下丘脑、垂体和肝脏成分进行了比较。与 Sst-/- 对照相比，雌性 Sst-/- 小鼠的垂体 GH mRNA 水平以及 GHRH 和 ghrelin 受体水平增加，这些变化通过循环 GH 和 IGF-I 的增加反映出来。雌性 Sst-/- 小鼠中 IGF-I 水平升高与肝脏 IGF-I、GH 和催乳素受体 mRNA 水平升高相关。与 GH/IGF-I 在下丘脑功能负反馈调节中的作用一致，雌性 Sst-/- 小鼠中 GHRH mRNA 水平降低，而皮质抑素 (CST) mRNA 水平未改变。与 SST 缺失对雌性 GH 轴功能的广泛影响相反，与 Sst-/- 对照相比，Sst-/- 雄性小鼠中只有循环 GH、下丘脑 CST 和肝催乳素受体表达上调。这些结果证实并扩展了 SST 对 GH 轴调节的性别二态性作用，并表明 CST（一种通过 SST 受体抑制 GH 分泌的神经肽）可能在维持 Sst-/- 雄性小鼠的 GH 轴功能中发挥代偿作用。
It has been previously reported that male and female somatostatin (SST) knockout mice (Sst-/-) release more GH, compared with Sst+/+ mice, due to enhanced GH-secretory vesicle release. Endogenous SST may also regulate GH secretion by directly inhibiting GHRH-stimulated GH gene expression and/or by modulating hypothalamic GHRH input. To begin to explore these possibilities and to learn more about the gender-dependent role of SST in modulating GH-axis function, hypothalamic, pituitary, and liver components of the GH-axis were compared in male and female Sst-/- and Sst-/- mice. Pituitary mRNA levels for GH and receptors for GHRH and ghrelin were increased in female Sst-/- mice, compared with Sst-/- controls, and these changes were reflected by an increase in circulating GH and IGF-I. Elevated levels of IGF-I in female Sst-/- mice were associated with elevated hepatic mRNA levels for IGF-I, as well as for GH and prolactin receptors. Consistent with the role of GH/IGF-I in negative feedback regulation of hypothalamic function, GHRH mRNA levels were reduced in female Sst-/- mice, whereas cortistatin (CST) mRNA levels were unaltered. In contrast to the widespread impact of SST loss on GH-axis function in females, only circulating GH, hypothalamic CST, and hepatic prolactin receptor expression were up-regulated in Sst-/- male mice, compared with Sst-/- controls. These results confirm and extend the sexually dimorphic role of SST on GH-axis regulation, and suggest that CST, a neuropeptide that acts through SST receptors to inhibit GH secretion, may serve a compensatory role in maintaining GH-axis function in Sst-/- male mice.