EVIDENCE FOR FIBROBLAST GROWTH-FACTOR MEDIATION OF COMPENSATORY ADRENOCORTICAL PROLIFERATION

The role of basic fibroblast growth factor (bFGF) in the neurally medi ated control of compensatory adrenocortical cell proliferation which o ccurs in response to unilateral adrenalectomy has been investigated. T hree isoforms of bFGF have been identified in the rat adrenal with Wes tern blots and bFGF immunoreactivity is most concentrated in the glome rulosa cells. A high affinity binding site (K-d=10pM) was identified i n primary cultures of rat glomerulosa cells. Using autoradiography of I-125-bFGF binding, in vivo bFGF binding sites were found concentrated in the glomerulosa as well as the capsule cells. The compensatory adr enocortical proliferation was blocked by suramin and bFGF receptor den sity appeared to be regulated during this proliferation. These results support a role for bFGF in autocrine and paracrine stimulation of pro liferation in the adrenal cortex and capsule. To specifically block th e receptor-mediated effect of bFGF in this response, we have developed an antisense strategy. Antisense oligodeoxynucleotide targeted agains t bFGF-receptor mRNA blocks the proliferative effect of bFGF in primar y glomerulosa cell cultures by approximately 50%. These results indica te that this antisense strategy interferes with the expression of bFGF -receptors and is an effective technique to reduce the proliferative e ffect of bFGF via the effect on its receptor.