Effect of Centrally Administered Insulin on Gonadotropin-Releasing Hormone Neuron Activity and Luteinizing Hormone Surge in the Diabetic Female Rat

Diabetic female rats have decreased ovulation, sexual behavior, and luteinizing hormone (LH) surges. Peripheral insulin treatment restores the phenotype to normal. We administered central insulin and analyzed serum LH during the time of the LH surge in diabetic and non-diabetic animals to determine if central insulin was sufficient to normalize the phenotype. We assessed the activity and number of hypothalamic gonadotropin-releasing hormone (GnRH) neurons by double label immunocytochemistry for c-Fos and GnRH to determine if decreased GnRH neuron activity or number could account for the diabetes-induced deficits in neuroendocrine function. All animals were ovariectomized and given estradiol and progesterone. Diabetic and control animals were given either intracerebroventricular (ICV) insulin or saline. In experiment I, serial blood collection was performed. In experiment II, animals were sacrificed and their brains were processed for immunocytochemistry during the presumed LH surge. Experiment I showed that diabetic, saline-treated animals were unable to trigger an LH surge. Central insulin restored LH production to control levels. Experiment II revealed similar numbers and activation of GnRH neurons in all four groups. Therefore, the diabetes-induced loss of the LH surge cannot be explained simply by a reduction of GnRH-expressing neurons or by a decrease in GnRH neuronal activity.