The role of androgen receptors in the medial amygdala on biosynthesis and stress-induced cellular activation of the paraventricular nucleus of the hypothalamus
Brenda Bingham, Megan Gray & Victor Viau
Although it is becoming increasingly clear that testosterone exerts an inhibitory influence on stress-induced adrenocorticotropin (ACTH) and corticosterone release, where and how this occurs in the brain remains poorly understood. We previously determined that androgen receptors are not distributed within anterior pituitary communicating neurons of the paraventricular nucleus (PVN) of the hypothalamus (Bingham et al. J Comp Neurol 2006). However, they are contained within several upstream brain regions involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and (ACTH) secretion. The medial amydala (MeA) concentrates androgen receptors and regulates the HPA response to acute restraint stress (Dayas et al. Eur J Neurosci, 2002). Furthermore, animals that are gonadectomized as neonates have higher levels of plasma corticosterone and Fos in the PVN under basal conditions and in response to restraint stress, despite equivalent adult testosterone replacement (Bingham & Viau, Endocrinology, 2008). Interestingly, these same animals showed a decrease in the number of androgen receptors in the MeA. Based on these findings, we are examining the role of androgen receptors contained within the MeA on the HPA response to a single episode of restraint. Adult male rats received bilateral implants of the androgen receptor antagonist hydroxyflutamide, or testosterone suspended in beeswax, aimed towards the MeA. Two weeks after surgery, animals were subjected to restraint stress for 30 min and anesthetized for perfusion 2 h following the onset of restraint. We are currently investigating the effects of these implants on PVN biosynthesis and cellular activation and hormonal output.