Time course of hypothalamic growth hormone-releasing hormone and somatostatin content in streptozocin diabetic rats: evidence for early changes in hypothalamic regulation

Abstract

Growth hormone secretion is markedly suppressed early in streptozocin induced diabetes mellitus of the rat. Our studies were designed to delineate early changes in hypothalamic regulation by growth hormone-releasing hormone (GHRH) and somatostatin (SS) with the aim of determining the best time period for hypothalamic secretion studies. Although hypothalamic GHRH content (ng/hypothalamus) and SS concentration (ng/mg wet weight) were unchanged at 17 to 20 days in previous studies, we anticipated changes earlier in the time course from transient imbalances in release and synthesis. We examined hypothalamic GHRH content and SS concentration in control, diabetic, and insulin treated diabetic rats (n = 5-13; streptozocin 100 mg/kg i.p.) at 0, 2, 4, 7, 10 and 21 days. In diabetic rats GHRH content was greater at day 2 (142 +/- 9% of control-same day, P < 0.05) and day 4 (139 +/- 17%, P < 0.05), but was less at day 10 (67 +/- 4%, P < 0.01). GHRH content of insulin treated diabetic rats was elevated at day 2 (158 +/- 10%, P < 0.05), but subsequently was unchanged from control. In diabetic rats SS concentration was decreased at day 4 (78 +/- 5%, P < 0.01) and at day 21 (91 +/- 3%, P < 0.05). Our results show earliest changes compared to control in GHRH content at 2 days and in SS concentration at 4 days. These findings support early changes in hypothalamic secretion, define a time period of 1 to 10 days for further studies of release and gene expression, and suggest complex relationships of gene expression, peptide synthesis, and peptide release.