Evidence for fibroblast growth factor mediation of compensatory adrenocortical proliferation

The role of basic fibroblast growth factor (bFGF) in the neurally mediated control of compensatory adrenocortical cell proliferation which occurs in response to unilateral adrenalectomy has been investigated. Three isoforms of bFGF have been identified in the rat adrenal with Western blots and bFGF immunoreactivity is most concentrated in the glomerulosa cells. A high affinity binding site (Kd = 10 pM) was identified in primary cultures of rat glomerulosa cells. Using autoradiography of 125I-bFGF binding, in vivo bFGF binding sites were found concentrated in the glomerulosa as well as the capsule cells. The compensatory adrenocortical proliferation was blocked by suramin and bFGF receptor density appeared to be regulated during this proliferation. These results support a role for bFGF in autocrine and paracrine stimulation of proliferation in the adrenal cortex and capsule. To specifically block the receptor-mediated effect of bFGF in this response, we have developed an antisense strategy. Antisense oligodeoxynucleotide targeted against bFGF-receptor mRNA blocks the proliferative effect of bFGF in primary glomerulosa cell cultures by approximately 50%. These results indicate that this antisense strategy interferes with the expression of bFGF-receptors and is an effective technique to reduce the proliferative effect of bFGF via the effect on its receptor.