HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN WBN KOB RATS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS/

In an attempt to define the hypothalamic-pituitary-adrenal (HPA) axis in non-insulin dependent diabetic rats (WBN/Kob), we measured plasma c orticotropin releasing factor (CRF), as well as arginine vasopressin ( AVP), ACTH, and corticosterone (B), CRF concentrations in the median e minence (ME), the remainder of the hypothalamus (rHY) and the neuroint ermediate lobe of the pituitary (NIL). We also measured Iodine-125-lab eled ovine CRF ([(129)]oCRF) binding in the brain and peripheral tissu es. Body and thymus weight in WBN/Kob rats were significantly lower th an in control Wistar rats, but adrenal weight was higher in WBN/Kob ra ts. Plasma ACTH levels were significantly higher in WBN/Kob rats than in the control rats. However, plasma CRF, AVP and B levels in WBN/Kob rats were not different from those in the control rats. The CRF concen tration was significantly decreased in the ME of the diabetic rats, co mpared with control rats, but CRF concentrations in the rHY and NIL we re unchanged in the two groups. A significant :reduction in [I-125]oCR F binding in the anterior pituitary was demonstrated in WBN/Kob rats, but no significant difference between the diabetic and control rats in CRF binding was observed in the frontal cortex, spleen or adrenal gla nd. These findings suggest that the HPA axis is chronically stimulated in the non-insulin dependent diabetic rats.