Effects of gonadectomy and testosterone replacement on number of dynorphin-immunoreactive (minusIR) cells in the arcuate nucleus of the hypothalamus in obese and diabetic male rats

BACKGROUND AND AIMS: Dynorphins (Dyn) are involved in the regulation of feeding and kisspeptin together with dynorphin and neurokinin B play a role in reproductive functions. Besides primary metabolic health problems occurring in people with obesity and/or diabetes, there are disruptions of the reproductive system (e.g. hypogonadism, infertility). Moreover, alterations in the hypothalamic dynorphin system in food deprived and diabetic animals were reported. However, there is no study looking at changes in number of Dyn-ir neurons in the arcuate nucleus of the hypothalamus (ARC), where integration of metabolism and reproduction may occur in obese and diabetic rats. There were 2 aims: (1) to assess if obesity induced by high fat diet and/or diabetes induced by injections of streptozotocin (STZ) alters the number of Dyn-ir neurons in the ARC in male rats; (2) to examine if gonadectomy (GDX) and testosterone (T) replacement differentially alters the number of Dyn-ir neurons in the ARC in male rats. METHODS: Rats were fed with high fat diet (HFD) or control (C) diet for 5 weeks. Injections of STZ were performed to induce diabetes type 1 (C/STZ) or diabetes type 2 (HFD/STZ) The following groups were obtained: C, C/STZ, HFD, HFD/STZ. Next, animals were divided into 3 groups: gonadectomy (GDX); gonadectomy and T replacement (GDX+T) and control (Sham). Immunocytochemistry for the Dyn was performed. RESULTS: Dynorphin-ir was found in: paraventricular nucleus of the hypothalamus, supraoptic nucleus, ventromedial nucleus, lateral hypothalamus, ARC and median eminence. Preliminary results indicate that there is a slight increase in number of Dyn-ir cells in C/ STZ and a slight decrease in HFD/STZ group. Currently data from GDX and GDX+T animals is analyzed. CONCLUSIONS: If data is confirmed on the bigger sample (currently analyzed), observed changes may contribute both to metabolic and reproductive deficits observed in these animals. Supported by grant NCN 2011/01/B/NZ4/04992.