Selective contributions of the medial preoptic nucleus to testosterone-dependant regulation of the paraventricular nucleus of the hypothalamus and the HPA axis. Abbreviated Title: Testosterone- and MPN-HPA interactions

Previous data have consistently demonstrated an inhibitory effect of androgens on stressinduced hypothalamic-pituitary-adrenal (HPA) responses. Several brain regions may influence androgen-mediated inhibition of the HPA axis, including the medial preoptic area. To test the role of the medial preoptic nucleus (MPN) specifically, we examined in highand low-testosterone replaced gonadectomized rats bearing discrete bilateral lesions of the MPN, basal and stress-induced indices of HPA function, and the relative levels of CRH and AVP mRNA in the amygdala. High testosterone replacement decreased plasma ACTH and PVN Fos responses to restraint exposure in sham-, but not in MPN-lesioned animals. AVP-, but not CRH-ir staining in the external zone of the median eminence was increased by testosterone in sham animals, and MPN lesions blocked this increment in AVP. A similar interaction between MPN lesions and testosterone occurred on AVP mRNA levels in the medial nucleus of the amygdala. These findings support an involvement of MPN projections in mediating the AVP response to testosterone in both the medial parvocellular PVN and medial amygdala. We conclude that the MPN forms part of an integral circuit that mediates the central effects of gonadal status on neuroendocrine and central stress responses. Key terms: corticotropin releasing hormone (CRH), arginine vasopressin (AVP), Fos, adrenocorticotropin (ACTH), corticosterone, medial amygdala.