Effects of Orchidectomy and Testosterone Replacement on Numbers of Kisspeptin-, Neurokinin B-, and Dynorphin A-Immunoreactive Neurones in the Arcuate Nucleus of the Hypothalamus in Obese and Diabetic Rats.

Neurones expressing kisspeptin, neurokinin B and dynorphin A, located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions depend on metabolic and hormonal status. We hypothesised that male rats with high-fat diet-induced obesity (DIO) and/or streptozotocin-induced diabetes mellitus type 1 (DM1) and type 2 (DM2) will have alterations in numbers of immunoreactive (-IR) cells: kisspeptin-IR and/or neurokinin B-IR and dynorphin A-IR neurones in the ARC in the sham condition. In addition, orchidectomy alone (ORX) and with testosterone treatment (ORX+T) will unmask possible deficits in the response of these neurones in DIO, and/or DM1 and DM2 rats. Rats were assigned to four groups: a control (C) and one diabetic group (DM1) were fed a regular chow diet, whereas the obese group (DIO) and the other diabetic group (DM2) were fed a high-fat diet. To induce diabetes, streptozotocin was injected. After 6 weeks, each group was divided into three subgroups: ORX, ORX+T and sham. After another 2 weeks, metabolic and hormonal profiles were assessed and immunocytochemistry was performed. We found that: (1) under sham conditions: (i) DM1 and DM2 animals had higher numbers of kisspeptin-IR cells than controls and (ii) DM2 rats had increased numbers of neurokinin B-IR and dynorphin A-IR cells compared to C animals; (2) ORX and ORX+T treatments unmasked deficits of the studied neurones in DM1 and DM2 but not in DIO animals; and (3) DIO, DM1 and DM2 rats had altered metabolic and hormonal profiles, in particular decreased levels of testosterone. We concluded that alterations in numbers of kisspeptin-IR and neurokinin B-IR neurones in the ARC and their response to ORX and ORX+T may account for disruptions of metabolic and reproductive functions in diabetic but not in obese rats.