Effect of hypophysectomy and growth hormone administration on hypothalamic growth hormone-releasing hormone and somatostatin content: Relationship to age-related growth rate

The purpose of these studies was to evaluate the effect of age-related differences in growth rate on the hypothalamic content of growth hormone-releasing factor (GHRH) and somatostatin (SS) and on the short loop feedback regulation of GHRH and SS. Percent weight gain, GHRH content, and SS content in control adolescent (8 weeks) and adult rats (6 months) were compared in normal rats administered supraphysiologic amounts of rat growth hormone (rGH) or in hypophysectomized rats receiving thyroxine and corticosterone with or without physiologic rGH replacement. In control adolescent rats, the rate of weight gain was 5-fold higher than in adult rats. GHRH content was higher in adolescent rats, while SS content was lower. After the administration of supraphysiologic amounts of rGH, GHRH content increased in adolescent rats but did not change in adult rats. SS content was unchanged in either age group. Following hypophysectomy GHRH content declined similarly in both groups, whereas the decrease in SS content was greater in adolescent rats. With replacement rGH, weight gain was restored, GHRH content increased but not fully to control, and SS content did not change. The ratio of SS content to GHRH content (SS/GHRH) was higher in control adult rats than in adolescent rats. SS/GHRH increased following hypophysectomy and returned to control values by rGH replacement. We conclude that age-related differences in growth rate are accompanied by appropriate changes in SS/GHRH and that SS and GHRH are regulated by short loop feedback at both ages with increased responses in adolescent rats. The inability of thyroxine, corticosterone, and rGH replacement to fully restore GHRH and SS content after hypophysectomy suggest that other factors contribute to the regulation of hypothalamic GHRH and SS.