EFFECTS OF SEX-HORMONES ON CYCLIC-NUCLEOTIDE METABOLISM IN CULTURED BOVINE AORTIC ENDOTHELIAL-CELLS

The effects of testosterone and estradiol on the regulation of the cyc lic nucleotide metabolism in primary cultured endothelial cells from b ovine aortae were examined. Testosterone added 24 h after plating incr eased the adenosine 3',5'-cyclic monophosphate (cAMP) concentration fr om 20.3 to 40.6 pmol/mg protein, whereas the guanosine 3',5'-cyclic mo nophosphate (cGMP) level decreased from 1.9 to 0.8 pmol/mg protein ove r a 5-day period. Estradiol increased cAMP from 20.3 to 30.3 pmol/mg p rotein and increased cGMP from 1.9 to 3.5 pmol/mg protein. The action of testosterone was potentiated by the addition of 10 mM theophylline. The basal level of the adenylate cyclase activity in control cells an d the elevated level in treated cells were stimulated by sodium fluori de. In the presence of isobutylmethylxanthine, prostacyclin produced t he most significant stimulation followed by isoproterenol and prostagl andin E(1). In contrast, phenylephrine failed to stimulate the adenyla te cyclase activity significantly. Testesterone added to subconfluent cultures at a low concentration (1 x 10(-9) M) failed to stimulate ade nylate cyclase, but did inhibit low-K-m phosphodiesterase (p < 0.05). A high concentration (1 x 10(-7) M) of testosterone stimulated the ade nylate cyclase activity, markedly decreased the activities of high- an d low-K-m phosphodiesterase, and caused a reduction in matrix fibronec tin, rearrangement of actin, and a change in cell surface topography. This study showed that testosterone induced a major change in endothel ial cell cyclic nucleotide metabolism by modulating the activities of adenylate cyclase and cAMP phosphodiesterase, whereas estradiol induce d a major change in cGMP metabolism.