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Laboratories for Neuroendocrinology, The Salk Institute La Jolla, California 92037
Address requests for reprints to: Dr. Mari Hotta, Laboratories for Neuroeridocrinology, Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037.
Abstract
Transforming growth factor-β (TGFβ) has a differential effect on the growth and function of bovine adrenocortical cells in vitro. TGFβ inhibits basal as well as ACTH- or angiotensin II-stimulated steroid formation, with no evidence of change in cell growth. The major inhibitory effect of TGFβ occurs at a step before cholesterol formation, since treatment of adrenocortical cells with TGFβ decreased not only 
4-steroid levels but also 5-steroid levels. The addition of cholesterol reverses the suppression of steroidogenesis induced by TGFβ. To determine the mechanism of this inhibition, the effect of TGFβ on low density lipoprotein (LDL) metabolism was investigated. Cells treated with TGFβ showed a significant suppression of [125I]iodohuman LDL ([125I]LDL) binding to the cell surface, followed by decreases in internalization and proteolytic degradation of [125I]LDL. Maximal inhibition of LDL metabolism was observed at a concentration of 1 ng/ml (4 x 10-11 M) TGFβ. The stimulation of LDL metabolism by ACTH was also inhibited by TGFβ, and the inhibition observed correlated well with the inhibition of steroidogenesis. The inhibitory effect of TGFβ on [125I]LDL binding results from the decrease in the maximal LDL-binding capacity. The stimulation of LDL uptake induced by BusjcAMP, cholera toxin, forskolin, and Ang II was also decreased by treatment with 1 ng/ml TGFβ. The specificity of this effect is quite high, since the inhibitory effects of TGFβ on LDL metabolism were not observed with either inhibin A or activin, two molecules that have considerable structural homology to TGFβ. We conclude that TGFβ specifically suppresses LDL metabolism in bovine adrenocortical cell cultures and that this step may mediate, at least in part, its role as a potent inhibitor of steroidogenesis. (Endocrinology 121: 150–159, 1987)
Footnotes
* This work was supported by program grants for the NIH (DK-18811 and HD-09690), The G. Harold and Leila Y. Mathers Charitable Foundation, and The Robert J. and Helen C. Kleberg Foundation.
Received December 16, 1986.
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