Estradiol or ovariectomy decreases CRF synthesis in hypothalamus

Gonadectomy and gonadectomy plus chronic estradiol administration decrease the content of hypothalamic corticotropin-releasing factor-like immunoreactivity (CRF-ir). This investigation was conducted to determine whether this was a result of chronic inhibition of CRF synthesis or stimulation of release. Administration of the protein synthesis inhibitor anisomycin one hour prior to sacrifice in otherwise untreated controls resulted in a 21% decrease in median eminence CRF-ir (p less than 0.01). Rats were ovariectomized and then administered either estradiol or vehicle daily for 3 weeks. Compared to vehicle-treated controls, estradiol treatment decreased CRF-ir in median eminence (p less than 0.01). In contrast to controls, administration of anisomycin to these ovariectomized rats did not significantly decrease median eminence CRF-ir in either the vehicle or estradiol-treated groups, implying that CRF synthesis was already depressed. Plasma adrenocorticotropin (ACTH) was increased by anisomycin treatment in all groups whether intact, ovariectomized or estradiol-treated (p less than 0.0005). Adrenal weights did not differ between these groups, or in comparison to sham-ovariectomized rats, indirectly implying lack of chronically elevated plasma ACTH. These data suggest that the mechanism for both the ovariectomy and chronic estradiol-induced decrease in CRF-ir content is an inhibition of CRF synthesis as opposed to a stimulation of CRF release.