When Gonads Talk to the Heart

Abstract

Pisa, ItalyCardiovascular risk is significantly lower in normally cycling women compared with men. This difference is abolished after menopause, suggesting a link with sex steroid hormones. Early studies on cardiac endocrine function disclosed higher natriuretic peptide concentrations in women than in men, suggesting the hypothesis that female sex steroid hormones could directly stimulate cardiomyocyte hormone production and secretion (1). Kuroski de Bold (2) hypothesized that an improved cardiovascular risk profile in cycling women could be associated with some estrogen stimulatory effect on cardiac endocrine function. Indeed, cardiac natriuretic peptides exert several protective actions on the heart and vessels, including: 1) vasodilatation; 2) promotion of diuresis/natriuresis; and 3) inhibition of hypertrophy, fibrosis, and apoptosis either directly or via inhibition of the sympathetic and renin-angiotensin-aldosterone systems, as well as the release or action of endothelin and vasopressin (1). See page 618More recently, 3 large population-based studies have indicated that male sex steroid hormones might modulate cardiac endocrine function too (3)(4)(5). These studies demonstrated a significant inverse association between the circulating levels of B-type natriuretic peptide (BNP) or N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) and male sex steroid hormones (i.e., total and free testosterone) in both sexes (3-5), whereas the association with estradiol was found to be weak or not significant at all (3,4). Furthermore, these studies reported that levels of sex hormone-binding globulin (SHBG) are positively associated with NT-proBNP levels in both male and female adolescents (4), as well as in adult women (3,5) and men (5). Testosterone and estradiol circulate in the bloodstream mostly bound to SHBG, with levels that directly influence bioavailability of sex hormones; only a small fraction of total steroid concentration is unbound or "free" (1% to 5%) and biologically active (i.e., able to enter a cell and activate its receptors).Lam et al. (5), in this issue of the Journal, evaluate plasma NT-proBNP, total testosterone, and SHBG concentrations in 4,056 adult men and women from the Framingham Heart Study Third-Generation Cohort; estradiol was not measured. They found lower NT-proBNP plasma levels in men than in age-matched women and higher NT-proBNP levels in women receiving hormonal contraceptives than in women who were not (5). Moreover, serum free (non-protein-bound) testosterone was positively and serum SHBG was negatively related to circulating NT-proBNP levels (5). The investigators suggested the hypothesis that androgens suppress NT-proBNP and that differences in free testosterone levels may largely explain the sex-and hormone-related differences in circulating levels of natriuretic peptides. They concluded that lower levels of circulating androgens and the potentiating effect of exogenous female hormone therapy contribute to the higher circulating NT-proBNP levels in women.These findi...

State of the art of immunoassay methods for B-type natriuretic peptides: An update

“…In order to explain these variations, the possible influence of sex steroid hormones on the cardiac natriuretic hormone system 90,93 , as well as changes in the cardiovascular system with age 96,97 , may need to be considered. Higher plasma BNP/NT-proBNP levels of women during the fertile adult period compared to men could be explained by the action of sex steroid hormones, as previously discussed in detail 13,93,98 . In healthy adult subjects, there is a gradual increase in both BNP and NT-proBNP after 65 years of age.…”

Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men

“…In humans and rats, ABP is produced in the liver [22], Sertoli and Leydig cells [55], and cardiomyocytes [31,56]. e physiological role of ABPs in peripheral tissues remains poorly understood; however, studies indicate that ABPs regulate the local bioavailability of androgens [56][57][58]. SHBG/ABPs are polypeptides of 43-44 kDa [20,50].…”