Androgens alter corticotropin releasing hormone and arginine vasopressin mRNA within forebrain sites known to regulate activity in the hypothalamic-pituitary-adrenal axis

To reveal direct effects of androgens, independent of glucocorticoids, we s tudied the effects of gonadectomy (GDX) in adrenalectomized (ADX) rats with or without androgen replacement on corticotropin releasing hormone (CRH) a nd arginine vasopressin (AVP) mRNA expression within various forebrain site s known to regulate the hypothalamic-pituitary-adrenal axis. These included the medial parvocellular portion of the paraventricular nucleus of the hyp othalamus (mp PVN), the central and medial nuclei of the amygdala and bed n uclei of the stria terminalis (BNST). In the mp PVN, ADX stimulated both CR H and AVP mRNA expression. Combined ADX + GDX inhibited only AVP, and testo sterone and dihydrotestosterone (DHT) restored AVP mRNA. In the central nuc leus of the amygdala, ADX decreased CRH mRNA expression, and this response was unaffected by GDX +/- testosterone or DHT replacement. In the medial am ygdala, AVP mRNA expression was decreased by ADX, abolished by ADX + GDX, a nd restored by androgen replacement. ADX had no effect on CRH and AVP mRNA expression in the BNST. GDX + ADX, however, reduced CRH mRNA expression onl y within the fusiform nuclei of the BNST and reduced the number of AVP-expr essing neurones in the posterior BNST. Androgen replacement reversed both r esponses. In summary, in ADX rats, AVP, but not CRH mRNA expression in the amygdala and mp PVN, is sensitive to GDX +/- androgen replacement. Both CRH - and AVP-expressing neurones in the BNST respond to GDX and androgen repla cement, but not to ADX alone. Because androgen receptors are not expressed by hypophysiotropic PVN neurones, we conclude that glucocorticoid-independe nt, androgenic influences on medial parvocellular AVP mRNA expression are m ediated upstream from the PVN, and may involve AVP-related pathways in the medial amygdala, relayed to and through CRH- and AVP-expressing neurones of the BNST.