Anatomically specific changes in the expression of somatostatin, growth hormone-releasing hormone and growth hormone receptor mRNA in diabetic rats

Growth hormone (GH) secretion is altered in poorly controlled diabetic anim als. However, modifications in the hypothalamic neuropeptides that control GH secretion, somatostatin and GH-releasing hormone (GHRH), as well as chan ges in the sensitivity of the hypothalamus and pituitary to the feedback ef fects of GH, are less clear. We have used RNase protection assays and in-si tu hybridization to address whether the mRNA expression of GH, somatostatin and GHRH, as well as of the GH receptor (GHR) in the hypothalamus and ante rior pituitary, are altered in streptozotocin-induced diabetic rats. After induction of diabetes, rats were treated with insulin twice daily for 3 wee ks to obtain either poorly controlled (mean plasma glucose > 300 mg/dl) or well-controlled diabetic rats. Although no significant change in pituitary GH mRNA expression was found, the hypothalamic expression of GHRH and somat ostatin mRNA was reduced in poorly-controlled diabetic rats and returned to control values with normalisation of plasma glucose concentrations (P < 0. 0001 and P < 0.002, respectively). Somatostatin mRNA expression was reduced only in the central portion of the periventricular nucleus, with no change being seen in the other areas of the periventricular nucleus or in the arc uate, suprachiasmatic or paraventricular nuclei. A significant decline in G HRH mRNA expression was observed in both the arcuate nucleus and ventromedi al hypothalamus. Anterior pituitary GHR mRNA expression was significantly r educed in both well and poorly-controlled diabetic rats, while there was no change in the hypothalamus. To examine whether the evolution time of the d iabetes influences these parameters, in a subsequent experiment, diabetic r ats received no insulin for 2 months. A significant decline in GHRH and som atostatin mRNA expression was also observed in these rats. In addition, pit uitary GH mRNA expression declined significantly in long-term diabetic rats . These results demonstrate that: (1) the expression of both GHRH and somat ostatin declines specifically in anatomical areas involved in anterior pitu itary hormone control; (2) GHR mRNA expression is decreased in the pituitar y of diabetic rats, but not in the hypothalamus, and does not return to con trol values with normalisation of mean blood glucose concentrations; and (3 ) the evolution time of the diabetes is important for detecting some change s, including the decrease in pituitary GH mRNA expression.