The Inhibition of Low Density Lipoprotein Metabolism by Transforming Growth Factor-β Mediates Its Effects on Steroidogenesis in Bovine Adrenocortical Cellsin Vitro*
- 1 July 1987
- journal article
- research article
- Published by The Endocrine Society in Endocrinology
- Vol. 121 (1), 150-159
- https://doi.org/10.1210/endo-121-1-150
Abstract
Transforming growth factor-.beta. (TGF.beta.) has a differential effect on the growth and function of bovine adrenocortical cells in vitro. TGF.beta. 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 TGF.beta. occurs at a step before cholesterol formation, since treatment of adrenocortical cells with TGF.beta. decreased not only .DELTA.4-steroid levels but also .DELTA.5-steroid levels. The addition of cholesterol reverses the suppression of steroidogenesis induced by TGGF.beta.. To determine the mechanism of this inhibition the effect of TGF.beta. on low density lipoprotein (LDL) metabolism was investigated. Cells treated with TGF.beta. showed a significant suppression of [12I]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 .times. 10-11 M) TGF.beta.. The stimulation of LDL metabolism by ACTH was also inhibited by TGF.beta., and the inhibition observed correlated well with the inhibition of steroidogenesis. The inhibitory effect of TGF.beta. on [125I]LDL binding results from the decrease in the maximal LDL-binding capacity. The stimulation of LDL uptake induce by Bu2cAMP, cholera toxin, forskolin, and Ang II was also decreased by treatment with 1 ng/l TGF.beta.. The specificity of this effect is quite high, since the inhibitory effects of TGF.beta.v on LDL metabolism were not observed with either inhibin A or activin, two molecules that have considerable structural homology to TGF.beta.. We conclude that TGF.beta. specifically suppresses LDL metabolism in bovine adrenortical cell cultures and that this step may mediate, at least in part, its role as a potent inhibitor of steroidogenesis.Keywords
This publication has 32 references indexed in Scilit:
- Effect of platelet-derived and endothelial cell-derived growth factors on the low density lipoprotein receptor pathway in cultured human fibroblasts.Journal of Biological Chemistry, 1982
- Regulation of low-density lipoprotein receptors in cultured bovine adrenocortical cellsArchives of Biochemistry and Biophysics, 1982
- Solid phase synthesis of somatostatin-28Biochemical and Biophysical Research Communications, 1980
- Platelet-derived growth factor stimulates activity of low density lipoprotein receptors.Proceedings of the National Academy of Sciences, 1980
- Low Density Lipoprotein Receptors in Bovine Adrenal Cortex. II. Low Density Lipoprotein Binding to Membranes Prepared from Fresh Tissue*Endocrinology, 1979
- Low Density Lipoprotein Receptors in Bovine Adrenal Cortex. I. Receptor-Mediated Uptake of Low Density Lipoprotein and Utilization of Its Cholesterol for Steroid Synthesis in Cultured Adrenocortical Cells*Endocrinology, 1979
- Receptor-mediated uptake of low density lipoprotein and utilization of its cholesterol for steroid synthesis in cultured mouse adrenal cells.Journal of Biological Chemistry, 1977
- Control of Bovine Adrenal Cortical Cell Proliferation by Fibroblast Growth Factor. Lack of Effect of Epidermal Growth FactorEndocrinology, 1977
- Lipoprotein-mediated regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesteryl ester metabolism in the adrenal gland of the rat.Journal of Biological Chemistry, 1977
- Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycansCell, 1976