Intracerebroventricular leptin regulates hepatic cholesterol metabolism.

To elucidate the control of hepatic cholesterol metabolism by leptin, rats were administered IV (intravenous) leptin, ICV (intracerebroventricular) leptin or saline. A single low dose of ICV leptin was as effective as a continuous IV infusion of high-dose leptin at decreasing the activities of 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7alpha-hydroxylase. These results indicate that the hepatic response to leptin is transduced via the central nervous system.

Central insulin administration maintains reproductive behavior in diabetic female rats.

Diabetic female rats have decreased ovulation, reproductive behavior and luteinizing hormone surges. Peripheral insulin treatment restores the phenotype to normal and also corrects many of the metabolic changes. To further evaluate the role of insulin in the specific maintenance of reproductive behavior, rather than administering it peripherally, we gave insulin intracerebroventricularly (ICV) at doses that did not correct the peripheral metabolic changes associated with diabetes such as hyperglycemia. During the experiment, we assessed the general activity and reproductive behavior of gonadectomized, estrogen- and progesterone-treated diabetic and control, nondiabetic female rats. Some of the animals received ICV saline, the rest received ICV insulin. General activity (ambulation, rearing and corner sniffing) was not affected by any of the treatments. Streptozotocin-induced diabetes resulted in a significantly decreased lordosis quotient, and ICV insulin was able to completely prevent this reduction. Furthermore, ICV insulin was able to cause a modest increase in the lordosis quotient among nondiabetic rats as well. Moreover, ICV insulin also increased the quality of lordosis among diabetic rats. Our results support a central role of insulin in the control of reproductive functions, beyond maintaining the homeostatic and metabolic balance.

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.