Guo F, Beaudet A, Tannenbaum G S
Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
Endocrinology. 1996 Sep;137(9):3928-35. doi: 10.1210/endo.137.9.8756568.
Although considerable evidence indicates that somatostatin (SRIF) exerts direct actions on GH-releasing hormone-containing arcuate neurons within the hypothalamus to modulate hypophyseal GH secretion, the underlying mechanism(s) remains to be elucidated. We recently demonstrated high levels of expression of the messenger RNAs (mRNAs) coding for two prototypic receptors of the recently cloned SRIF receptor (sst) family, sst1 and sst2, in the arcuate nucleus of the rat hypothalamus. However, information on the biological roles of these receptor subtypes and the factors regulating their expression is lacking. In the present study, we hypothesized that perturbations in GH would influence sst mRNA levels in cells of the arcuate nucleus in vivo. To test this hypothesis, we examined the effects of hypophysectomy (HPX) and HPX with GH replacement, on sst1 and sst2 mRNA levels in the brains of adult male rats by in situ hybridization using 35S-labeled antisense riboprobes. The number of labeled cells and the density of silver grains per cell were quantified using a computer-assisted image analysis system. Two weeks after HPX, there was a 50-60% reduction in both the number and labeling density of sst1 and sst2 mRNA-expressing cells in the arcuate nucleus compared to those in sham-operated control rats. Administration of recombinant human GH (200 micrograms/day for 7 days by continuous sc infusion using osmotic minipumps) to HPX rats augmented both the cell number (P < 0.05) and labeling density (P < 0.01) of sst1 mRNA in the arcuate nucleus, but did not significantly alter sst2 mRNA levels compared to those in HPX rats infused with H2O. There were no significant changes in sst1 and sst2 mRNA levels in extra-arcuate areas, including the cerebral cortex and medial habenula, or in suprachiasmatic, medial preoptic, and magnocellular preoptic nuclei after either HPX or GH replacement. These results indicate that the expression of both sst1 and sst2 SRIF receptor subtypes in brain is under the regulatory influence of pituitary hormones. They further suggest that GH may participate in the regulation of its own secretion by influencing the expression of the sst1 receptor gene on arcuate neurons. Such a mechanism may be important in the feedback regulation of GH secretion by the arcuate nucleus.
尽管大量证据表明，生长抑素（SRIF）可直接作用于下丘脑内含有生长激素释放激素的弓状神经元，以调节垂体生长激素的分泌，但其潜在机制仍有待阐明。我们最近发现，在大鼠下丘脑弓状核中，编码最近克隆的生长抑素受体（sst）家族的两种原型受体sst1和sst2的信使核糖核酸（mRNA）表达水平很高。然而，关于这些受体亚型的生物学作用以及调节其表达的因素的信息却很缺乏。在本研究中，我们假设生长激素的扰动会影响体内弓状核细胞中sst mRNA的水平。为了验证这一假设，我们通过使用35S标记的反义核糖探针进行原位杂交，研究了垂体切除术（HPX）以及垂体切除术后生长激素替代对成年雄性大鼠脑中sst1和sst2 mRNA水平的影响。使用计算机辅助图像分析系统对标记细胞的数量和每个细胞的银粒密度进行了量化。垂体切除术后两周，与假手术对照组大鼠相比，弓状核中表达sst1和sst2 mRNA的细胞数量和标记密度均减少了50% - 60%。给垂体切除的大鼠连续皮下注射重组人生长激素（使用渗透微型泵，每天200微克，共7天），可增加弓状核中sst1 mRNA的细胞数量（P < 0.05）和标记密度（P < 0.01），但与注射水的垂体切除大鼠相比，sst2 mRNA水平没有显著变化。垂体切除或生长激素替代后，在包括大脑皮层和内侧缰核在内的弓状核外区域，以及视交叉上核、内侧视前核和大细胞视前核中，sst1和sst2 mRNA水平均无显著变化。这些结果表明，大脑中sst1和sst2生长抑素受体亚型的表达受垂体激素的调节影响。它们进一步表明，生长激素可能通过影响弓状神经元上sst1受体基因的表达来参与自身分泌的调节。这种机制可能在弓状核对生长激素分泌的反馈调节中起重要作用。
