[Autocrine regulation of adrenal steroidogenesis by growth factor transforming TGF-beta 1]

Abstract

Transforming growth factor beta (TGF beta) is a multifunctional polypeptide presenting various biological activities depending on the cellular context where it is studied. In the adrenal cortex, TGF beta is a potent inhibitor of corticosteroïdogenesis. The sum of data that we have collected in the past years has allowed us to establish that TGF beta (in particular TGF beta 1) is implicated in a physiological autocrine/paracrine regulatory loop. We determined that primary cultures of bovine fasciculatareticularis cells synthesize and secrete about 5 ng/24 h x 10(6) cells of TGF beta but that most of this activity is under a latent form. In the adrenal gland, TFG beta 1 could be localized in the fasciculata-reticularis zone by immunohistochemistry. We also reported that adrenocortical cells possess type I and type III (betaglycan) receptors, whose number is positively regulated by ACTH. Moreover, we have identified 3 major targets of TGF beta in our cell model: cytochrome P-450(17) alpha (17 alpha-hydroxylase) whose gene expression is decreased, angiotensin II receptors and LDL receptors whose number is reduced after TGF beta treatment. As a conclusion, TGF beta appears to participate together with other regulatory peptides (IGF-1, TNF alpha) in the fine tuning of corticosteroid secretion levels which are under the major control of the hypothalamo-pituitary axis.