DYNAMICS AND MECHANICS OF CORTICOSTEROID FEEDBACK AT HYPOTHALAMUS AND ANTERIOR-PITUITARY GLAND

Corticosteroid feedback mechanisms were investigated at the hypothalamic level using the rat hypothalamus in vitro and at the pituitary level using basal hypothalamic-lesioned rats. Both fast and delayed corticosteroid feedback effects were demonstrated at the level of the hypothalamus and pituitary gland with doses of corticosteroids within or near the physiological range. These 2 phases of feedback were separated temporally by a silent period during which no feedback was apparent. Studies on the mechanism of action of corticosteroids at the hypothalamic level showed that the fast feedback mechanism acts by inhibition of release while the delayed feedback mechanism acts by inhibition of both synthesis and release. The fast feedback action of corticosterone does not appear to act by excitation of neuroinhibitory pathways since neither picrotoxin nor phentolamine prevented the feedback action of corticosteroids in vitro. Corticosterone inhibition of corticotrophin releasing factor release was overcome by depolarization of the membrane with K+ suggesting that the mechanism of action of the fast feedback of corticosteroids is by membrane stabilization.