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

Abstract To reveal direct effects of androgens, independent of glucocorticoids, we studied the effects ofgonadectomy (GDX) in adrenalectomized (ADX) rats with or without androgen replacement oncorticotropin releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression withinvarious forebrain sites known to regulate the hypothalamic-pituitary-adrenal axis. These included themedial parvocellular portion of the paraventricular nucleus of the hypothalamus (mp PVN), the centraland medial nuclei of the amygdala and bed nuclei of the stria terminalis (BNST). In the mp PVN,ADX stimulated both CRH and AVP mRNA expression. Combined ADX+GDX inhibited only AVP,and testosterone and dihydrotestosterone (DHT) restored AVP mRNA. In the central nucleus of theamygdala, ADX decreased CRH mRNA expression, and this response was unaffected byGDXttestosterone or DHT replacement. In the medial amygdala, AVP mRNA expression wasdecreased by ADX, abolished by ADX+GDX, and restored by androgen replacement. ADX had noeffect on CRH and AVP mRNA expression in the BNST. GDX+ADX, however, reduced CRH mRNAexpression only within the fusiform nuclei of the BNST and reduced the number of AVP-expressingneurones in the posterior BNST. Androgen replacement reversed both responses. In summary, inADX rats, AVP, but not CRH mRNA expression in the amygdala and mp PVN, is sensitive toGDXtandrogen replacement. Both CRH- and AVP-expressing neurones in the BNST respond toGDX and androgen replacement, but not to ADX alone. Because androgen receptors are notexpressed by hypophysiotropic PVN neurones, we conclude that glucocorticoid-independent,androgenic inﬂuences on medial parvocellular AVP mRNA expression are mediated upstream fromthe PVN, and may involve AVP-related pathways in the medial amygdala, relayed to and throughCRH- and AVP-expressing neurones of the BNST.Hypothalamic-pituitary-adrenal (HPA) responses to homeo-static insults are initiated by stimulatory inputs conveyingstress-related information to medial parvocellular (mp)neurosecretory neurones of the paraventricular nucleus ofthe hypothalamus (PVN). During stress, mp neurones releaseseveral peptides from their terminal stores into the portalcapillary zone of the median eminence and these subsequentlystimulate the release of adrenocorticotropin (ACTH) fromanterior pituitary corticotropes (1). Foremost among thesepeptides are corticotropin releasing hormone (CRH) andarginine vasopressin (AVP), which potentiates the stimul-atory effects of CRH on ACTH secretion. While someCRH-producing neurones coexpress AVP, the amount ofAVP synthesized under basal conditions is normally low, andis dependent on the state of the organism (2). AVP synthesis isupregulated in CRH-expressing neurones following glucocor-ticoid removal by adrenalectomy and in response to chronicstress. Thus, increased AVP synthesis and release are thoughtto sustain ACTH release, which is otherwise inhibited by thenegative feedback actions of elevated glucocorticoid levels.Gonadal inﬂuences on basal and stress function in the HPAaxis appear to be particular to AVP-expressing parvocellularneurosecretory neurones in the PVN. Thus, the dose-relatedinhibitory effect of testosterone on the magnitude of ACTH