Evidence that danazol inhibits gonadotropin-induced ovarian steroidogenesis at a point distal to gonadotropin-receptor interaction and adenosine 3′,5′ cyclic monophosphate formation

Abstract

The action of danazol on 125I-human chorionic gonadotropin (hCG) binding, gonadotropin-stimulated adenosine 3′,5′ cyclic monophosphate (cAMP) accumulation and progesterone production has been investigated in luteinized rat ovaries. Preincubation of luteal cells for short periods of time with increasing concentrations of danazol caused a significant inhibition of gonadotropin-stimulated steroidogenesis. The inhibitory effect of danazol was both concentration and time dependent. Danazol also reduced progesterone production in response to cholera enterotoxin and 8 bromo-adenosine-cAMP, but it had no effect on hCG, luteinizing hormone, and cholera enterotoxin stimulated cAMP formation. Similarly danazol did not affect 125I-hCG binding as assessed by the equilibrium dissociation constant (Kd) and number of hormone-binding sites on the luteal cell surface. These results suggest that in intact luteal cells danazol inhibits steroidogenesis at a point distal to hormone-receptor interaction and cAMP formation.