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.
