Bertherat J, Timsit J, Bluet-Pajot M T, Mercadier J J, Gourdji D, Kordon C, Epelbaum J
Institut National de la Santé et de la Recherche Médicale (INSERM) U 159, Centre Paul Broca, Paris, France.
J Clin Invest. 1993 Apr;91(4):1783-91. doi: 10.1172/JCI116389.
Effects of growth hormone (GH) hypersecretion on somatostatin-(SRIH) and GH-releasing hormone (GHRH) were studied by in situ hybridization and receptor autoradiography in rats bearing a GH-secreting tumor. 6 and 18 wk after tumor induction, animals displayed a sharp increase in body weight and GH plasma levels; pituitary GH content was reduced by 47 and 55%, while that of prolactin and thyrotropin was unchanged. At 18 wk, hypothalamic GHRH and SRIH levels had fallen by 84 and 52%, respectively. In parallel, the density of GHRH mRNA per arcuate neuron was reduced by 52 and 50% at 6 and 18 wk, while SRIH mRNA levels increased by 71 and 83% in the periventricular nucleus (with no alteration in the hilus of the dentate gyrus). The numbers of GHRH- and SRIH-synthetizing neurons in the hypothalamus were not altered in GH-hypersecreting rats. Resection of the tumor restored hypothalamic GHRH and SRIH mRNAs to control levels. GH hypersecretion did not modify 125I-SRIH binding sites on GHRH neurons. Thus, chronic GH hypersecretion affects the expression of the genes encoding for GHRH and SRIH. The effect is long lasting, not desensitizable and reversible.
采用原位杂交和受体放射自显影技术，研究了生长激素（GH）分泌过多对生长抑素（SRIH）和生长激素释放激素（GHRH）的影响，实验对象为患有分泌GH肿瘤的大鼠。肿瘤诱发后6周和18周，动物体重和血浆GH水平急剧增加；垂体GH含量分别降低了47%和55%，而催乳素和促甲状腺激素的含量未变。18周时，下丘脑GHRH和SRIH水平分别下降了84%和52%。与此同时，6周和18周时，每个弓状核神经元的GHRH mRNA密度分别降低了52%和50%，而室旁核中的SRIH mRNA水平则分别增加了71%和83%（齿状回 hilus 无变化）。GH分泌过多的大鼠下丘脑GHRH和SRIH合成神经元数量未改变。切除肿瘤后，下丘脑GHRH和SRIH mRNA恢复到对照水平。GH分泌过多未改变GHRH神经元上的125I-SRIH结合位点。因此，慢性GH分泌过多会影响编码GHRH和SRIH的基因表达。这种影响是持久的、不可脱敏的且可逆的。
