Effects of Organotin Compounds on Follicular Steroidogenesis in Frogs
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Some organotin compounds such as butyltins and phenyltins are known to induce impo-sex in various marine animals and are considered to be endocrine disruptors. In this study, the effect of organotins on follicular steroidogenesis in amphibians was examined using ovarian follicles of Rana dybowskii and Rana catesbeiana. Isolated follicles were cultured for 6 or 18 h in the presence and absence of frog pituitary homogenate (FPH) or various steroid precursors, and the levels of product steroids in the culture media were measured by radioimmunoassay. Among the butyltin compounds, tributyltin (TBT) strongly and dose-dependently inhibited the FPH-induced synthesis of pregnenolone (P5) and progesterone (P4) by the follicles. TBT also strongly suppressed the conversion of cholesterol to P5 and partially suppressed the conversion of P5 to P4. A high concentration of dibutyltin (DBT) also inhibited steroidogenesis by the follicles while monobutyltin and tetrabutyltin had negligible effects. The toxic effect of TBT or DBT was irreversible and a short time of exposure (30 min) was enough to suppress steroidogenesis. All the phenyltin compounds significantly inhibited FPH-induced P5 synthesis by the follicles. The effective dose of 50% inhibition by diphenyltin was 0.04 μM and those of monophenyltin and triphenyltin were 0.24 ㎛ and 0.3 μM, respectively. However, none of the phenyltin compounds significantly suppressed the conversion of P4 to 17α-hydroxyprogesterone (17α-OHP) (by 17α-hydroxylase), 17α-OHP to androstenedione (AD) (by C17-20 lyase), or AD to testosterone by the follicles. Taken together, the data show that among the steroidogenic enzymes, p450scc in the follicles is the most sensitive to organotin compounds and that an amphibian follicle culture system can be a useful screening model for endocrine disruptors.
Abstract
Some organotin compounds such as butyltins and phenyltins are known to induce impo-sex in various marine animals and are considered to be endocrine disruptors. In this study, the effect of organotins on follicular steroidogenesis in amphibians was examined using ovarian follicles of Rana dybowskii and Rana catesbeiana. Isolated follicles were cultured for 6 or 18 h in the presence and absence of frog pituitary homogenate (FPH) or various steroid precursors, and the levels of product steroids in the culture media were measured by radioimmunoassay. Among the butyltin compounds, tributyltin (TBT) strongly and dose-dependently inhibited the FPH-induced synthesis of pregnenolone (P5) and progesterone (P4) by the follicles. TBT also strongly suppressed the conversion of cholesterol to P5 and partially suppressed the conversion of P5 to P4. A high concentration of dibutyltin (DBT) also inhibited steroidogenesis by the follicles while monobutyltin and tetrabutyltin had negligible effects. The toxic effect of TBT or DBT was irreversible and a short time of exposure (30 min) was enough to suppress steroidogenesis. All the phenyltin compounds significantly inhibited FPH-induced P5 synthesis by the follicles. The effective dose of 50% inhibition by diphenyltin was 0.04 μM and those of monophenyltin and triphenyltin were 0.24 ㎛ and 0.3 μM, respectively. However, none of the phenyltin compounds significantly suppressed the conversion of P4 to 17α-hydroxyprogesterone (17α-OHP) (by 17α-hydroxylase), 17α-OHP to androstenedione (AD) (by C17-20 lyase), or AD to testosterone by the follicles. Taken together, the data show that among the steroidogenic enzymes, p450scc in the follicles is the most sensitive to organotin compounds and that an amphibian follicle culture system can be a useful screening model for endocrine disruptors.
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