Estradiol and the feeding state modulate the interaction between leptin and the nitrergic system in female rats

• Published in: Neuropeptides (Edinburgh) 2020-12, Vol.84, p.102096-102096, Article 102096
• Main Authors: Oliveira, L.L.B., Del Bianco-Borges, Bruno, Franci, C.R.
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Energy balance; Estradiol; Fasting; Feeding state; Gene expression; Gonadotropin-releasing hormone; Gonadotropins; Hypothalamus; Hypothalamus (medial); Hypothalamus (ventromedial); Immunohistochemistry; Interneurons; Leptin; Leptin receptors; Medial basal hypothalamus; Medial preoptic area; Nitric oxide; Nitric-oxide synthase; Ovariectomy; Perfusion; Pituitary (anterior); Polymerase chain reaction; Preoptic area; Receptor mechanisms; Rodents; Transcription; Western blotting
• ISSN: 0143-4179; 1532-2785
• DOI: 10.1016/j.npep.2020.102096

Leptin mediates the interaction between reproductive function and energy balance. However, leptin receptors are not expressed in neurons that produce gonadotropin-releasing hormone (GnRH), likely indicating an indirect action through interneurons. Among likely neurons that modulate the secretion of GnRH are NO (nitric oxide) neurons. We assessed whether estradiol and feeding conditions modulate a possible interaction between leptin and NO in brain areas related to the control of reproductive function. Estradiol-treated and untreated ovariectomized rats were normally fed or fasted for 48 h. Then, saline (control) or leptin (3 μg/1 μl) intracerebroventricular microinjections were administered, and after thirty minutes, the brains collected subsequent to the decapitation or transcardially perfusion. Leptin and estradiol increased NO synthase (nNOS) gene expression (RT-PCR) and content (Western blotting) in the medial preoptic area (MPOA) and medial basal hypothalamus (MBH) only in fasted rats. Leptin increased: 1-phosphorylated-signal transducer and activator of transcription-3(pSTAT3) (immunohistochemistry) in the MPOA and various hypothalamic nuclei [arcuate (ARC); ventromedial (VMH); dorsal/ventral dorsomedial (dDMH/vDMH); premammilar ventral (PMV)], effects potentiated by estradiol/fasting interaction; 2- nNOS/pSTAT3 coexpression in the MPOA only in estradiol-treated, fasted rats; 3- nNOS-immunoreactive cell expression in the VMH, DMH and PMV (areas related to reproductive function control) of estradiol -treated rats. Thus, when leptin is reduced during fasting, leptin replacement effectively increased the expression of nitric oxide, which activated the HPG axis only in the presence of estradiol. Estradiol modulates the nitrergic system, leptin sensitivity and consequently leptin's effects on the nitrergic system in hypothalamus and in particular vDMH and PMV. •Estradiol and leptin act together to increase nNOS gene expression in the MPOA in fasting condition.•Estradiol and leptin act together to increase nNOS protein content in the MPOA in fasting condition.•Leptin increased pSTAT3 in the MPOA, VMH, DMH and PMV.•nNOS and pSTAT3 are colocalized in the same cells in the MPOA, VMH, DMH and PMV.