THE EFFECTS OF SEX STEROIDS ON PLASMA-LEVELS OF MARKER PROTEINS OF ENDOTHELIAL-CELL FUNCTIONING

We studied thirteen male-to-female (M-->F) and ten female-to-male (F-- >M) transsexuals who, for four months, received cross-sex treatment wi th, respectively, ethinylestradiol and cyproterone acetate, and with t estosterone esters. We assessed the effects of treatment on plasma lev els of tissue-type plasminogen activator (tPA), von Willebrand factor (VWF), vWF-propeptide (vWF:AgII) and big-endothelin-1 (big-ET-l)? four proteins that are markers of endothelial cell functioning. We also me asured urokinase-type PA (uPA) and plasminogen activator inhibitor-typ e 1 (PAI-1), which may not be endothelium-derived but share major clea rance pathways with tPA. In M-->F transsexuals, mean plasma levels of tPA (minus 4.4 ng/ml), big-ET-l (minus 0.8 pg/ml), uPA (minus 0.5 ng/m l) and PAI-1 (minus 26 ng/ml) decreased tall Ps less than or equal to 0.02). The level of vWF increased (plus 24%; P = 0.005), while vWF:AgI I did not change (P = 0.49). In F-->M transsexuals, levels of big-ET-l increased (plus 0.4 pg/ml; P = 0.02), while tPA, uPA and PAI-I did no t change tall Ps >0.25). In this group vWF decreased (minus 14%; P = 0 .06). but vWF:AgII did not change (P = 0.38). Estrogens and androgens have clear effects on plasma levels of endothelial marker proteins. Th e mechanisms behind these effects are complex and appear to involve bo th altered secretion (big-ET-l) and processing and/or clearance (vWF a nd possibly tPA). Therefore, effects of hormones on the levels of endo thelial marker proteins do nor necessarily reflect changes in endothel ial cell functioning, at least with regard to changes in vWF level ass ociated with the oral administration of high doses of ethinylestradiol and cyproterone acetate to healthy men and the parenteral administrat ion of testosterone to healthy women.