ESTROGENS DECREASE EXPRESSION OF THE CORTICOTROPIN-RELEASING FACTOR GENE IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS AND OF THE PROOPIOMELANOCORTIN GENE IN THE ANTERIOR-PITUITARY OF OVARIECTOMIZED RATS

It is known that estrogens modulate the hypothalamopituitary-adrenal ( HPA) axis both under resting conditions and during exposure to stress. Nevertheless, the site of action of estrogens is not still fully eluc idated. We sought to determine if estrogens could act on the major hyp othalamic ACTH secretagogue: corticotropin-releasing factor (CRF). Mat ure rats were ovariectomized (OVX) and 2 weeks later implanted with si lastic capsules containing 17 beta-estradiol (E(2)). Animals were sacr ificed 7 days later. CRF mRNA in the hypothalamic paraventricular nucl eus (PVN) and proopiomelanocortin (POMC) mRNA in the anterior pituitar y were measured by in situ hybridization. CRF content in the median em inence was measured by semiquantitative immunocytochemistry. E(2) trea tment induced a significant decrease of CRF mRNA levels in the PVN (3. 70 +/- 0.14 vs 4.79 +/- 0.15 copies of probe x 10(-3)/mu m(3) of tissu e in OVX rats, P<0.05), an accumulation of immunoreactive CRF in the z one externa of the median eminence (207 +/- 36 vs 100 +/- 15% in OVX r ats, P<0.05), and a decrease of POMC mRNA levels in the anterior pitui tary (4.6 +/- 0.6 vs 6.9 +/- 0.6 copies of probe X 10(-2)/mu m(3) of t issue in OVX rats, P<0.05). These results demonstrate that estrogens h ave a negative effect on CRF gene expression and secretion and on POMC gene expression. Whether estrogens modulate directly the CRF-synthesi zing cells or act through an increase of the glucocorticoid negative f eedback remains to be determined.