GONADAL-STEROIDS EXERT FACILITATING AND BUFFERING EFFECTS ON GLUCOCORTICOID-MEDIATED TRANSCRIPTIONAL REGULATION OF CORTICOTROPIN-RELEASING HORMONE AND CORTICOSTEROID RECEPTOR GENES IN RAT-BRAIN

Gonadal steroids profoundly influence several brain functions and are apparently responsible for gender-specific differences in the regulati on of hypothalamic-pituitary-adrenal (HPA) secretions. In this study, we examined the so-called ''activational'' effects of gonadal steroids on the glucocorticoid-mediated regulation of the gene transcription o f corticotropin-releasing hormone (CRH) and corticosteroid receptors i n brain areas of relevance for the control of pituitary-adrenal secret ion. The efficacy of adrenalectomy (ADX) and chronic treatment with hi gh doses of corticosterone (B) to regulate the gene transcription of C RH and corticosteroid receptors in the hypothalamic paraventricular nu cleus (PVN) and hippocampus was studied in male and female rats under the conditions of deprivation of gonadectomy (GDX) and replacement wit h different gonadal steroids, such as estradiol (E(2)), progesterone ( P), and dihydrotestosterone (DHT). In both sexes, ADX alone or in comb ination with GDX increased, and B treatment suppressed, the steady-sta te levels of CRH and corticosteroid receptor mRNAs, whereas GDX alone failed to affect any of the parameters studied. Administration of gona dal hormones to steroid-deprived (ADX/GDX) animals partially attenuate d the upregulation of mRNAs encoding corticosteroid receptors in the h ippocampus, Supplementation with gonadal steroids modified the effects of B on the gene transcription of CRH and corticosteroid receptors. W hereas P alone or in combination with E(2) counteracted the B-induced downregulation of GR and CRH gene transcription in females, DHT and E( 2) administration further potentiated the effects of B on these parame ters in a sex-specific manner, Taken together, the results indicate th at gonadal steroids have minor influence on MR, GR, and CRH gene trans cription under basal conditions, exert ''glucocorticoid-like'' effects on the transcription of corticosteroid receptors in the hippocampus o f steroid-deprived animals, and interact with glucocorticoid-mediated mechanisms of regulation in the HPA axis through gender-specific ''buf fering'' and ''potentiating'' effects.