Endocrinology Research Group, MRC Clinical Research Centre, Watford Road, Harow HA1 2UJ, UK.
J Neuroendocrinol. 1991 Dec 1;3(6):661-8. doi: 10.1111/j.1365-2826.1991.tb00331.x.
Abstract The mechanisms by which the pituitary gland, and growth hormone (GH) in particular, affect growth hormone-releasing factor (GRF) gene expression have been addressed using the technique of in situ hybridization. Anatomically matched sections through the mediobasal hypothalamus of control and hypophysectomized male rats, with or without GH hormone replacement, were analysed to obtain information on GRF mRNA levels within the arcuate nucleus and around the ventromedial hypothalamus. Hypophysectomy resulted in a 70% increase in the amount of GRF mRNA per cell (P<0.001), within neurons in the arcuate nucleus. GH replacement and T4 replacement separately partially attenuated this increase (GH replacement P< 0.001 versus hypophysectomy, T4 replacement P<0.05 versus hypophysectomy). Additionally, after hypophysectomy there was an 80% increase in the number of cells expressing the GRF gene in neurons around the ventromedial hypothalamus, when compared to shamoperated controls (P<0.01). Both GH and T4 replacement separately partially attenuated this phenomenon (P<0.01 versus hypophysectomized animals). Hypothyroidism alone did not affect GRF mRNA levels in either the arcuate nucleus or in the area surrounding the ventromedial hypothalamus. These results show that hypophysectomy increases GRF mRNA levels in two separate ways: by increasing the amount of mRNA produced per cell within the arcuate nucleus, and by increasing the number of cells expressing the gene in the area surrounding the ventromedial hypothalamus. This increase in the number of GRF mRNA-containing cells after hypophysectomy could result from the recruitment of neurons which previously did not express the GRF gene, and may reflect the plasticity of the adult central nervous system in response to a changing endocrine environment. This could represent part of a sensor mechanism to drive the production of GRF in the arcuate nucleus in response to extreme disruption of the GRF/ GH feedback loop.
摘要
利用原位杂交技术研究了垂体，特别是生长激素（GH）影响生长激素释放因子（GRF）基因表达的机制。对对照和垂体切除雄性大鼠的中脑基底部的解剖匹配切片进行了分析，以获得弓状核内和腹内侧下丘脑周围的 GRF mRNA 水平的信息。垂体切除导致每个细胞的 GRF mRNA 增加 70%（P<0.001），在弓状核内的神经元中。GH 替代和 T4 替代分别部分减弱了这种增加（GH 替代 P<0.001 与垂体切除相比，T4 替代 P<0.05 与垂体切除相比）。此外，与假手术对照相比，垂体切除后，腹内侧下丘脑周围神经元中表达 GRF 基因的细胞数量增加了 80%（P<0.01）。GH 和 T4 替代分别部分减弱了这种现象（与垂体切除动物相比 P<0.01）。单独的甲状腺功能减退症对弓状核或腹内侧下丘脑周围区域的 GRF mRNA 水平没有影响。这些结果表明，垂体切除以两种不同的方式增加 GRF mRNA 水平：通过增加弓状核内每个细胞产生的 mRNA 量，以及通过增加腹内侧下丘脑周围区域表达基因的细胞数量。垂体切除后 GRF mRNA 含量增加的细胞数量可能是由于先前不表达 GRF 基因的神经元的募集，并且可能反映了成年中枢神经系统对不断变化的内分泌环境的可塑性。这可能是一种传感器机制的一部分，以驱动在 GRF/ GH 反馈回路受到极端破坏时在弓状核中产生 GRF。
