Department of Cell Biology, Physiology, and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba, and Centro de Investigacion Biomedica en Red Fisiopatología de la Obesidad y Nutrición, Cordoba, Spain.
Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E46-54. doi: 10.1152/ajpendo.00514.2010. Epub 2010 Oct 13.
Somatostatin (SST) inhibits growth hormone (GH) secretion and regulates multiple processes by signaling through its receptors sst1-5. Differential expression of SST/ssts may contribute to sex-specific GH pattern and fasting-induced GH rise. To further delineate the tissue-specific roles of SST and sst1-5 in these processes, their expression patterns were evaluated in hypothalamus, pituitary, and stomach of male and female mice under fed/fasted conditions in the presence (wild type) or absence (SST-knockout) of endogenous SST. Under fed conditions, hypothalamic/stomach SST/ssts expression did not differ between sexes, whereas male pituitary expressed more SST and sst2A/2B/3/5A/5TMD2/5TMD1 and less sst1, and male pituitary cell cultures were more responsive to SST inhibitory actions on GH release compared with females. This suggests that local pituitary SST/ssts can contribute to the sexually dimorphic pattern of GH release. Fasting (48 h) reduced stomach sst2A/B and hypothalamic SST/sst2A expression in both sexes, whereas it caused a generalized downregulation of pituitary sst subtypes in male and of sst2A only in females. Thus, fasting can reduce SST sensitivity across tissues and SST input to the pituitary, thereby jointly contributing to enhance GH release. In SST-knockout mice, lack of SST differentially altered sst subtype expression levels in both sexes, supporting an important role for SST in sex-dependent control of GH axis. Evaluation of SST, IGF-I, and glucocorticoid effects on hypothalamic and pituitary cell cultures revealed that these hormones could directly account for alterations in sst2/5 expression in the physiological states examined. Taken together, these results indicate that changes in SST output and sensitivity can contribute critically to precisely define, in a tissue-dependent manner, the sex-specific metabolic regulation of the GH axis.
生长抑素（SST）通过其受体 sst1-5 信号转导抑制生长激素（GH）的分泌并调节多种过程。SST/ssts 的差异表达可能有助于性别特异性 GH 模式和禁食诱导的 GH 升高。为了进一步描绘 SST 和 sst1-5 在这些过程中的组织特异性作用，在存在（野生型）或不存在（SST 敲除）内源性 SST 的情况下，评估了雄性和雌性小鼠在下丘脑中 SST/ssts 的表达模式。在喂养条件下，下丘脑/胃 SST/ssts 的表达在性别之间没有差异，而雄性垂体表达更多的 SST 和 sst2A/2B/3/5A/5TMD2/5TMD1，并且更少的 sst1，并且雄性垂体细胞培养物对 SST 抑制 GH 释放的作用比雌性更敏感。这表明局部垂体 SST/ssts 可以有助于 GH 释放的性别二态模式。禁食（48 小时）降低了两性的胃 sst2A/B 和下丘脑 SST/sst2A 表达，而在雄性中导致了垂体 sst 亚型的普遍下调，而在雌性中仅导致 sst2A 的下调。因此，禁食可以降低整个组织的 SST 敏感性和 SST 对垂体的输入，从而共同促进 GH 释放。在 SST 敲除小鼠中，缺乏 SST 以不同的方式改变了两性的 sst 亚型表达水平，支持 SST 在性别依赖性控制 GH 轴中的重要作用。评估 SST、IGF-I 和糖皮质激素对下丘脑和垂体细胞培养物的影响表明，这些激素可以直接解释在研究的生理状态下 sst2/5 表达的变化。总之，这些结果表明 SST 输出和敏感性的变化可以极大地有助于以组织依赖的方式精确定义 GH 轴的性别特异性代谢调节。
