SUN-476 Corticosterone-Mediated Suppression of the Reproductive Neuroendocrine Axis in Male Mice

Abstract

It is well identified that psychosocial stress disturbs reproductive hormone secretion at multiple levels of the reproductive axis. The neural and hormonal mechanisms underlying this reproductive suppression and the role of reproductive brain neuropeptides in this process is not fully understood. We previously showed that in gonadectomized (GDX) male mice, a one-time acute restraint stress strongly suppressed in vivo luteinizing hormone (LH) pulsatility within 12-18 min of stress initiation. Furthermore, similarly stressed GDX mice showed a rise in circulating corticosterone (CORT) levels by 15 min. These correlative data suggest that CORT may be an important signaling factor involved in the stress-induced suppression of LH pulses. Thus, the objective of the current work is to identify the role of CORT in mediating stress inhibition of the reproductive neuroendocrine axis. First, we performed a dose-response and time course study to determine an effective exogenous CORT treatment paradigm to mimic endogenous CORT levels during psychosocial stress. Next, to assess CORT effects on LH pulses, GDX male mice were pulse bled every 6 min for 90 min, then injected with either an oil vehicle or 1 mg/kg CORT, and pulse bled every 6 min for another 90 min. CORT-injected mice showed a reduction in LH pulses, though not as robust or for as long as in restraint stressed mice. These data suggest that while CORT is sufficient to decrease LH pulsatile secretion, additional factors may also be involved to achieve maximal stress-induced suppression. To determine if upstream neuroendocrine signaling of stimulatory (kisspeptin) and inhibitory (RFRP-3) neurons to GnRH neurons are involved in this CORT-mediated suppression, in situ hybridization was conducted in brains of vehicle- and CORT-injected mice to determine changes in Kiss1 and Rfrp mRNA content and neuronal activation. These data are currently being analyzed. Our findings suggest that while acute CORT is capable of moderately suppressing reproductive hormone secretion, it is not the only mechanism involved during psychosocial stress exposure. Future studies will need to investigate additional factors that are important.