Mechanism of Stress-Induced Reproductive Suppression

这项研究提出的广泛问题是：压力如何抑制生殖？ 压力抑制生殖的一种方式是通过减少垂体前叶促性腺激素的分泌。 重要的是，皮质醇，这是一种激素分泌的肾上腺皮质在增加的数额在压力，抑制促性腺激素分泌在非压力的绵羊时，交付的数额，模拟血浆皮质醇浓度在压力。 本研究项目的第一个组成部分使用生理学方法来检验假设，即血浆皮质醇增加对于抑制经历现实生活中的心理社会压力的绵羊的促性腺激素分泌是必不可少的（例如，隔离、禁闭、捕食者线索）。 然后，通过测试应激诱导的促性腺激素分泌抑制是否是通过II型糖皮质激素受体介导的，以及应激是否会降低垂体对促性腺激素释放激素的反应性，来解决潜在的机制。 细胞和分子的方法和垂体细胞培养系统，然后将被用来区分行动的皮质醇在质膜细胞内的行动，并确定是否皮质醇诱导的抑制促性腺激素分泌与垂体细胞上的促性腺激素释放激素受体减少。 这项研究将提供重要的新的洞察力的整合和细胞机制，即压力抑制繁殖绵羊通过证明皮质醇，通过II型糖皮质激素受体作用于垂体前叶细胞，是必不可少的应激诱导的促性腺激素分泌抑制。这反过来又具有全球意义，因为它可以提高绵羊在农业上重要的地区的粮食和纤维产量。 它还影响圈养或栖息地恶化条件下濒危物种的保护，并广泛影响生育调节。 这项研究还将有利于新的研究人员的专业发展，为本科生，研究生和博士后学员提供研究机会。

The broad question addressed by this research is: how does stress inhibit reproduction? One way stress acts to inhibit reproduction is by reducing secretion of gonadotropic hormones from the anterior lobe of the pituitary gland. Of importance, cortisol, which is a hormone secreted by the adrenal cortex in increased amounts during stress, suppresses gonadotropin secretion in non-stressed sheep when delivered in amounts that mimic plasma cortisol concentrations during stress. The first component of this research project uses a physiological approach to test the hypothesis that increased plasma cortisol is essential for suppression of gonadotropin secretion in sheep experiencing real-life psychosocial stressors (e.g., isolation, confinement, predator cues). It then addresses underlying mechanism by testing if stress-induced suppression of gonadotropin secretion is mediated via the type II glucocorticoid receptor, and if stress acts to reduce responsiveness of the pituitary gland to gonadotropin-releasing hormone. Cellular and molecular approaches and a pituitary-cell culture system will then be employed to distinguish actions of cortisol at the plasma membrane from intracellular actions, and to determine if cortisol-induced suppression of gonadotropin secretion is linked to reduced receptor for gonadotropin-releasing hormone on pituitary cells. This research will provide important novel insight into both integrative and cellular mechanisms whereby stress inhibits reproduction in sheep by demonstrating that cortisol, acting via the type II glucocorticoid receptor on cells of the anterior pituitary gland, is essential for stress-induced suppression of gonadotropin secretion. This, in turn, has global relevance as it could lead to enhanced food and fiber production in regions where sheep are agriculturally important. It also impacts preservation of endangered species maintained in captivity or in conditions of deteriorating habitat, and it bears broadly on fertility regulation. This research will also benefit professional development of new investigators by providing research opportunities for undergraduate, graduate and postdoctoral trainees.