GROWTH-HORMONE REGULATES AT-1A ANGIOTENSIN RECEPTORS IN ASTROCYTES

The hypothesis, based on previous in vivo data, that angiotensin AT1 r eceptors are regulated by GH or insulin-like growth factor I (IGF-I) h as been investigated in this study using primary cultures of rat astro cytes as a model of AT1 receptor expression. At a dose of 1 ng/ml GH, there was an increase in AT1 density within 4 h and a maximum increase of 361 +/- 57% of the control value at 12 h. At 24 h, receptor densit y was still 176 +/- 23% that in the control. Astrocytes incubated with 1 ng/ml rat IGF-I for 24 h showed no change in AT1 receptor density. Reverse transcriptase-PCR was used to show that astrocytes express bot h the AT1a receptor subtype and, to a much lesser extent, the AT1b sub type. Treatment with 1 ng/ml recombinant bovine GH for 12 h increased the messenger RNA of the AT1a receptor by 170%, without affecting the AT1b receptor. Inhibition of protein synthesis by cycloheximide and of transcription by the adenosine analog dichlororibofuranosylbenzimidaz ole both prevented the increase in AT1 receptor density following GH t reatment, indicating that the action of GH is transcriptional. In summ ary, we have shown that GH up-regulates, directly and not via IGF-I, a ngiotensin receptors of the AT1a subtype in astrocytes by a transcript ional mechanism. The long latency of the response and the dependency o n transcription relegate the AT1a gene to the class of GH-regulated ge nes identified as delayed stable genes. This mechanism of AT1 activati on may be one way in which GH activates the renin-angiotensin system a nd initiates consequential cardiovascular and angiogenic effects.