UC San Diego

Stress is a condition experienced by all living organisms. Stress can initiate psychological and physiological responses that may inhibit other systems in the body, including the reproductive system. Infertility is a concern for many individuals, and previous research has found a correlation between infertility and stress. In the mouse model, stress can inhibit normal reproductive function; however, the neural mechanisms mediating this phenomenon are not yet fully understood. The paraventricular nucleus (PVN) is a key region activated during the response to stress and this nucleus contains corticotropin releasing hormone (CRH) neurons. Evidence supports a CRH receptor type 2 pathway to play a key role in stress-induced suppression of reproductive function. Therefore, we hypothesized that urocortin 2 (UCN2), a neuropeptide in the CRH family with high affinity for CRH receptor type 2, may be a good candidate for a mediator of stress-induced suppression of the LH surge. We observed that central administration of UCN2 was sufficient to block an estradiol-induced LH surge. Next, we looked upstream at a population of norepinephrine (NE) producing neurons in the A2 region of the nucleus of the solitary tract in the brainstem. The A2NE population is known to be activated during a variety of stress types, and ablation of this population restores reproductive function in a hypoglycemic stress model. We hypothesized that this population was involved in stress induced reduction of reproductive function, and we observed that chronic activation of the A2NE population was sufficient to inhibit estrous cyclicity. In summary, these data support a working model whereby A2NE neurons can activate UCN2 cells in the PVN and initiate reproductive suppression during stress.