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.

中文翻译：

---

雌二醇和摄食状态调节雌性大鼠瘦素和硝能系统之间的相互作用

瘦素介导生殖功能和能量平衡之间的相互作用。然而，瘦素受体在产生促性腺激素释放激素 (GnRH) 的神经元中不表达，这可能表明通过中间神经元的间接作用。调节 GnRH 分泌的可能神经元包括 NO（一氧化氮）神经元。我们评估了雌二醇和喂养条件是否会调节与控制生殖功能相关的大脑区域中瘦素和 NO 之间可能的相互作用。雌二醇治疗和未治疗的去卵巢大鼠通常被喂食或禁食 48 小时。然后，给予生理盐水（对照）或瘦素（3μg/1μl）脑室内显微注射，三十分钟后，在斩首或经心灌注后收集大脑。瘦素和雌二醇仅在禁食大鼠中增加内侧视前区 (MPOA) 和内侧基底下丘脑 (MBH) 的 NO 合酶 (nNOS) 基因表达 (RT-PCR) 和含量 (Western 印迹)。瘦素增加：MPOA 和各种下丘脑细胞核中的 1-磷酸化信号转导和转录激活因子 3（pSTAT3）（免疫组织化学）腹内侧（VMH）；背/腹背内侧 (dDMH/vDMH); 前乳头腹侧 (PMV)]，雌二醇/禁食相互作用增强的作用；2-nNOS/pSTAT3 在 MPOA 中的共表达仅在雌二醇治疗的禁食大鼠中；雌二醇处理的大鼠的 VMH、DMH 和 PMV（与生殖功能控制相关的区域）中的 3-nNOS 免疫反应性细胞表达。因此，当禁食期间瘦素减少时，瘦素替代品有效地增加了一氧化氮的表达，仅在雌二醇存在时激活 HPG 轴。雌二醇调节氮能系统、瘦素敏感性，从而调节瘦素对下丘脑氮能系统的影响，尤其是 vDMH 和 PMV。