BASIC FIBROBLAST GROWTH-FACTOR MAY MEDIATE PROLIFERATION IN THE COMPENSATORY ADRENAL GROWTH-RESPONSE

We have investigated the role of basic fibroblast growth factor (bFGF) in the neurally mediated compensatory adrenal growth response. Unilateral adrenalectomy resulted in a 13, 6, and 22% increase in adrenal weight, protein, and DNA content, respectively, and 33-40% increases in the rate of cell proliferation measured by [H-3]thymidine incorporation in vitro. Three forms of bFGF, approximately 18.6, 21, and 22.5 kDa, were identified in rat adrenals by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. bFGF was localized immunocytochemically in cells of the glomerulosa and the medulla. bFGF stimulated a 68-80% increase in the rate of DNA synthesis in adrenal capsule-glomerulosa preparations in vitro. Suramin (0.1 mM), a growth factor antagonist, blocked bFGF receptor interaction in vitro and, at 200 mg/kg given 5-7 days before adrenal surgery, blocked compensatory growth. Conversely, at 2.0 mg/kg, suramin significantly enhanced the compensatory growth response, perhaps caused by suramin-induced bFGF receptor upregulation, since suramin pretreatment also enhanced DNA synthesis in response to exogenous bFGF in vitro. These results suggest that bFGF may mediate proliferation in the compensatory adrenal growth response.