ENDOCRINE CONTROL OF THE DISTRIBUTION OF BASIC FIBROBLAST GROWTH-FACTOR, INSULIN-LIKE GROWTH-FACTOR-I AND TRANSFORMING GROWTH FACTOR-BETA(1) MESSENGER-RNAS IN ADULT-RAT ADRENALS USING NONRADIOACTIVE IN-SITU HYBRIDIZATION

This study located the particular cell types involved in the synthesis of growth factors in adult female rat adrenal glands. Non-isotopic in situ hybridization was used and the cellular localizations of the mRN As of basic fibroblast growth factor (bFGF), IGF-I, and transforming g rowth factor-beta(1) (TGF-beta(1)) were studied in adrenals from contr ol animals and from those treated with ACTH or subjected to dietary so dium restriction. The adrenal medulla was the richest source of both b FGF and IGF-I mRNA in both control and experimental rat adrenals. In t he cortex, bFGF and IGF-I mRNAs were found mainly in the zona fascicul ata in control animals, although some transcription was also detected in the zona reticularis and zona glomerulosa. Both ACTH and sodium res triction activated bFGF and IGF-I gene expression in the zona glomerul osa. Since cellular proliferation and differentiation occur primarily in the outer cortex, the data are consistent with the view that bFGF a nd IGF-I act as an autocrine/paracrine mitogen and differentiation reg ulator respectively in the rat adrenal cortex. Very small amounts of T GF-beta(1) mRNA were detected, predominantly in the zona fasciculata o f control rats. There were no observable differences in amounts and lo calization of TGF-beta(1) mRNA between the adrenals of control rats an d those treated with ACTH for 1 day. TGF-beta(1) mRNA was very weak or undetectable in the adrenals from rats treated with ACTH for three an d five days or from sodium-restricted rats. Although TGF-beta(1) immun oreactive protein has been shown to be present in the zonae fasciculat a and reticularis and to modulate negatively the steroidogenic activit ies in the adrenal cortex of other species, its gene is not actively e xpressed in rat adrenals. The present results showed that ACTH adminis tration or dietary sodium restriction, both important adrenal mitogens in vivo, significantly altered the spatial patterns of the distributi on of bFGF and IGF-I mRNAs and also increased the amount of bFGF mRNA in the adrenal cortex. This suggests that growth and differentiation o f the adrenal cortex are partly mediated by bFGF and IGF-I.