The Effects of Sex Steroids on Plasma Levels of Marker Proteins of Endothelial Cell Functioning

Abstract

SummaryWe studied thirteen male-to-female (M→F) and ten female-to-male (F→M) transsexuals who, for four months, received cross-sex treatment with, respectively, ethinylestradiol and cyproterone acetate, and with testosterone esters. We assessed the effects of treatment on plasma levels of tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), vWF-propeptide (vWF:AgII) and bigendothelin-1 (big-ET-1), four proteins that are markers of endothelial cell functioning. We also measured urokinase-type PA (uPA) and plasminogen activator inhibitor-type 1 (PAI-1), which may not be endothelium-derived but share major clearance pathways with tPA.In M→F transsexuals, mean plasma levels of tPA (minus 4.4 ng/ml), big-ET-1 (minus 0.8 pg/ml), uPA (minus 0.5 ng/ml) and PAI-1 (minus 26 ng/ml) decreased (all Ps ≤0.02). The level of vWF increased (plus 24%; P = 0.005), while vWF:AgII did not change (P = 0.49).In F→M transsexuals, levels of big-ET-1 increased (plus 0.4 pg/ml; P = 0.02), while tPA, uPA and PAI-1 did not change (all 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. The mechanisms behind these effects are complex and appear to involve both altered secretion (big-ET-1) and processing and/or clearance (vWF and possibly tPA). Therefore, effects of hormones on the levels of endothelial marker proteins do not necessarily reflect changes in endothelial cell functioning, at least with regard to changes in vWF level associated with the oral administration of high doses of ethinylestradiol and cyproterone acetate to healthy men and the parenteral administration of testosterone to healthy women.

Impact of androgen-induced oxidative stress on hypertension in male SHR

“…Furthermore, androgens may have indirect effects on oxidative stress via other systems, such as the renin-angiotensin system or the endothelin systems. Androgens have been shown in SHR to upregulate angiotensinogen expression by us and others (8), and androgen supplements increase plasma endothelin levels in humans (26). Alternatively, androgens may differentially impact the other NADPH oxidase isoforms in the kidney contributing to differences in NADPH oxidase subunit expression and superoxide production.…”

Sex and gender differences in control of blood pressure

“…Testosterone also increases angiotensinogen synthesis in the kidney (59,60), which could increase renin enzyme activity. Androgens have also been shown to increase endothelin levels in transsexuals taking masculinizing levels of testosterone (61). …”

Hypertension alone or related to the metabolic syndrome in postmenopausal women

“…There are several ways in which androgens could impact BP. Testosterone supplementation in rats stimulates production of angiotensinogen, the substrate for renin, in the kidney, activating the RAS [9]; androgen supplementation in women is also associated with increased plasma endothelin [10]. Thus, androgens could play a role in postmenopausal hypertension by affecting the RAS, endothelin or oxidative stress.…”