Effects of Ovariectomy and Sex Hormone Replacement on Numbers of Kisspeptin-, Neurokinin B- and Dynorphin A-immunoreactive Neurons in the Arcuate Nucleus of the Hypothalamus in Obese and Diabetic Rats

• Published in: Neuroscience Vol. 451; pp. 184 - 196
• Main Authors: Ziarniak, Kamil, Kołodziejski, Paweł A., Pruszyńska-Oszmałek, Ewa, Dudek, Monika, Kalló, Imre, Sliwowska, Joanna H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15.12.2020
• Subjects: Animals; Arcuate Nucleus of Hypothalamus - metabolism; diabetes; Diabetes Mellitus, Experimental; Dynorphins - metabolism; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone - metabolism; high-fat diet; Kisspeptins; KNDy neurons; Male; Neurokinin B - metabolism; Neurons - metabolism; Obesity; Ovariectomy; Rats; reproduction; HPG axis; NKB; P4; AVPV; KP; HFD; E2; OVX; TG; ORX; high-fat diet; ipGTT; DYN A; diabetes; ovariectomy; KNDy neurons; reproduction
• DOI: 10.1016/j.neuroscience.2020.10.003
• ISSN: 0306-4522

•Results suggest that metabolic cues disrupt female reproductive functions by acting in the arcuate nucleus (ARC).•The metabolic and hormonal status affect differentially the kisspeptin, neurokinin B and dynorphin cells in the ARC.•Neither the metabolic status nor the gonadal hormonal changes affect the number of kisspeptin-ir cells in the ARC.•The gonadal hormonal changes affect the number of neurokinin B-ir cells in the ARC regardless of the metabolic status.•Robust effects of the metabolic status and the gonadal hormonal changes were observed on dynorphin A-ir neurons in DM2. KNDy neurons co-expressing kisspeptin (KP), neurokinin B (NKB) and dynorphin A (DYN A) in the arcuate nucleus of the hypothalamus (ARC) are key regulators of reproduction. Their activity is influenced by metabolic and hormonal signals. Previously, we have shown that orchidectomy alters the KP-, NKB-, and DYN A-immunoreactivity in the high-fat diet-induced (HFD) obesity and diabetes type 2 (DM2) models. Considering the potential sex difference in the response of KNDy neurons, we have hypothesized that ovariectomy (OVX) and post-ovariectomy replacement with estradiol (OVX+E2) or estradiol and progesterone (OVX+E2+P4) will also affect these neurons in HFD and DM2 females. Thus, each of these treatment protocols were employed for control, HFD, and DM2 groups of rats leading to nine experimental conditions within which we have determined the number of KP-, NKB-, or DYN-immunoreactive (-ir) neurons and assessed the metabolic and hormonal profiles of the animals. Accordingly: (1) no effects of group and surgery were observed on the number of KP-ir neurons; (2) the overall number of NKB-ir neurons was higher in the OVX+E2+P4 and OVX+E2 animals compared to OVX; (3) overall, the number of DYN A-ir neurons was higher in DM2 vs. control group, and surgery had an effect on the number of DYN A-ir neurons; (4) the metabolic and hormonal profiles were altered in HFD and DM2 animals compared to controls. Current data together with our previously published results indicate sex-specific differences in the response of KNDy neurons to DM2.