Instituto de Biología y Medicina Experimental-CONICET, Argentina.
Instituto de Biología y Medicina Experimental-CONICET, Argentina; Universidad de Buenos Aires, Facultad de Medicina, Departamento de Fisiología y Biofísica, Buenos Aires, Argentina.
Peptides. 2018 Jan;99:117-127. doi: 10.1016/j.peptides.2017.04.006. Epub 2017 Apr 23.
Orexins A/B derived from hypothalamic prepro-orexin (PPO) are agonists for orexin receptors 1 (OX1) and 2 (OX2). Previously, we showed clear sex differences in the hypothalamic-pituitary-gonadal orexinergic system in adult rodents. Here, we studied the effect of sexual brain differentiation on the orexinergic system in neuroendocrine structures regulating reproduction. We evaluated: a: proestrous and neonatally androgenized female rats; b: adult males, untreated or gonadectomized in adulthood and injected with oil or estradiol and progesterone (E/P); c: control and demasculinized males (perinatally treated with flutamide and later castration) injected either with oil or E/P in adulthood. Rats were sacrificed at 12:00 and 18:00h; blood samples and brains were collected. Hormones were measured using radioimmunoassay. PPO, OX1 and OX2 mRNAs were quantified by qPCR in medial basal hypothalamus, anterior hypothalamus, adenohypophysis, and cortex. Western blots for OX1 were done in the same structures. In normal females, gonadotropins surged at 18:00h coinciding with significant elevations of PPO, OX1 and OX2 mRNAs and OX1 protein in hypothalamus and pituitary; no increases were observed at noon. Afternoon changes were absent in masculinized females. Demasculinized males when treated with E/P showed high PPO, OX1 and OX2 mRNAs and OX1 protein expression in hypothalamus and pituitary at 12:00 and 18:00h compared vehicle-treated controls. The same steroid treatment was ineffective in males with normal brain masculinization. Here we show that neonatal testosterone shapes the sexual differences in the hypothalamic-pituitary orexinergic system in synchronicity to establishing the brain sex differences of the reproductive axis. The female brain controls gonadotropin surges and concurrent elevations of all studied components of the orexinergic system, suggesting its participation as a possible link between food intake, behavior and hormonal control of reproduction.
下丘脑前脑啡肽原（PPO）衍生的食欲素 A/B 是食欲素受体 1（OX1）和 2（OX2）的激动剂。先前，我们在成年啮齿动物的下丘脑-垂体-性腺食欲素能系统中发现了明显的性别差异。在这里，我们研究了性脑分化对调节生殖的神经内分泌结构中食欲素能系统的影响。我们评估了：a：发情前期和新生期雄激素化雌性大鼠；b：成年雄性，未处理或成年后性腺切除术，并注射油或雌二醇和孕酮（E/P）；c：对照和去势雄性（围产期用氟他胺处理，然后去势），成年后注射油或 E/P。大鼠在 12:00 和 18:00 时处死；采集血液样本和大脑。使用放射免疫测定法测量激素。在中脑基底部、下丘脑前部、腺垂体和皮质中通过 qPCR 定量 PPO、OX1 和 OX2 mRNA。在相同结构中进行 OX1 的 Western blot。在正常雌性中，促性腺激素在 18:00 时激增，同时下丘脑和垂体中的 PPO、OX1 和 OX2 mRNA 以及 OX1 蛋白显著升高；中午没有观察到增加。下午变化在雄性化雌性中不存在。用 E/P 治疗去势雄性时，与对照组相比，下丘脑和垂体中的 PPO、OX1 和 OX2 mRNA 以及 OX1 蛋白表达在 12:00 和 18:00 时升高。在具有正常大脑男性化的雄性中，相同的类固醇治疗无效。在这里，我们表明，新生期睾酮塑造了下丘脑-垂体食欲素能系统中的性别差异，与生殖轴的大脑性别差异同步建立。女性大脑控制促性腺激素激增和所有研究的食欲素能系统成分的同时升高，表明其参与作为食物摄入、行为和激素对生殖的控制之间的可能联系。
