Abstract
Neurons 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 hypothesized 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: 1) alterations in numbers of immunoreactive (ir) cells: kisspeptin-ir and/or neurokinin B-ir, and dynorphin A-ir neurons in the ARC in the sham condition; 2) orchidectomy alone (ORX) and with testosterone treatment (ORX+T) will unmask possible deficits in the response of these neurons 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, while 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 condition: i) DM1 and DM2 animals had higher numbers of kisspeptin-ir cells than controls; 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 neurons in DM1 and DM2 but not in DIO animals; 4) 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 neurons 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.
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