Inhibition of gonadotropin-releasing hormone receptors in rat anterior pituitary monolayer cell cultures by danazol

Mangaladevi Menon, Helle Peegel, Viswanatham Katta
In: American Journal of Obstetrics and Gynecology · 1986 · vol. 154(2) , pp. 367–372 · doi:10.1016/0002-9378(86)90673-3 · PMID:3004220 · W2019178774
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Danazol inhibits gonadotropin-releasing hormone receptor binding in rat anterior pituitary cells.

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Abstract

To study possible cellular antigonadotropic effects of danazol, monolayer cultures of anterior pituitary cells from immature female rats were treated with danazol. Measurements of luteinizing hormone release in response to 10(-8) mol/L gonadotropin-releasing hormone challenge and iodine 125-labeled gonadotropin-releasing hormone binding activity were done after exposure to increasing concentrations of danazol and for increasing lengths of time. It was found that luteinizing hormone secreted by pituitary cells in response to gonadotropin-releasing hormone was inhibited after danazol treatment in a dose- and time-dependent manner when compared to controls. Also, a 45% decrease in gonadotropin-releasing hormone receptor binding capacity was observed in pituitary cells cultured in the presence of increasing concentrations of danazol in the range of 10(-8) to 10(-4) mol/L when compared to controls. Furthermore, exposure to danazol for 25 to 96 hours caused a marked decrease in gonadotropin-releasing hormone binding activity (p less than 0.005). Under these experimental conditions danazol treatment decreased the pituitary receptors for gonadotropin-releasing hormone in a dose- and time-dependent manner. Scatchard analysis of saturation curves for the binding of gonadotropin-releasing hormone to cellular gonadotropin-releasing hormone receptors indicated that the observed decrease in gonadotropin-releasing hormone binding in the danazol-treated group was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. It is therefore concluded that the antigonadotropic activity of danazol appears to be related to a decrease in gonadotropin-releasing hormone receptors in the pituitary.

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