GONADAL-STEROIDS EXERT FACILITATING AND BUFFERING EFFECTS ON GLUCOCORTICOID-MEDIATED TRANSCRIPTIONAL REGULATION OF CORTICOTROPIN-RELEASING HORMONE AND CORTICOSTEROID RECEPTOR GENES IN RAT-BRAIN
Vk. Patchev et Ofx. Almeida, GONADAL-STEROIDS EXERT FACILITATING AND BUFFERING EFFECTS ON GLUCOCORTICOID-MEDIATED TRANSCRIPTIONAL REGULATION OF CORTICOTROPIN-RELEASING HORMONE AND CORTICOSTEROID RECEPTOR GENES IN RAT-BRAIN, The Journal of neuroscience, 16(21), 1996, pp. 7077-7084
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.