Feedback effects of gonadal steroids and pituitary LH-releasing hormone receptors in the streptozotocin-induced diabetic rat.

The effects of streptozotocin (STZ)-induced diabetes mellitus on the positive feedback action of steroids on luteinizing hormone (LH) secretion have been investigated in the oestrogen-primed ovariectomized rat. Rats treated with 40 mg/kg STZ 2 weeks before experimentation showed an attenuated LH surge in response to progesterone, an effect only partially restored by insulin replacement. When the same dose of the drug was injected just 24 h before the progesterone treatment it had no effect on the LH surge, while a high dose of 80 mg/kg STZ completely abolished the positive feedback action of the steroid. Insulin treatment did not reverse this effect. In parallel the effects of 2-week and 24-h diabetes on pituitary LH-releasing hormone (LRH) receptors were studied. Pituitary binding of a long acting LRH analogue was reduced in the 2-week diabetic animals, although a more dramatic reduction was observed in the rats treated with the high dose of STZ 24 h before testing. The results suggest that diabetes impairs the positive feedback effects of gonadal steroids resulting in a reduced release of LRH. However, the impairment is unlikely to be caused simply by hyperglycaemia but by non-specific toxic side effects of STZ and/or other metabolic changes associated with diabetes.