Sex Differences in Umbilical Cord Serum Levels of Inhibin, Testosterone, Oestradiol Dehydroepiandrosterone Sulphate, and Sex Hormone-Binding Globulin in Human Term Neonates

Abstract

The contribution of the fetus to inhibin production in human pregnancy is unclear. Previous studies have reported inhibin concentrations in cord blood but on limited sample numbers. The present study is a more extensive examination of sex differences in immunoreactive inhibin and steroidal hormones in term umbilical cord blood. Venous serum concentrations of inhibin were found to be significantly higher in males (mean ± SD 2,168 ± 914 pg/ml, n = 62) than in females (1,761 ± 951 pg/ml, n = 63) (p < 0.01). Male concentrations of total testosterone (p < 0.005), free testosterone (p < 0.005), and estradiol (p < 0.05) were also significantly higher. The concentration of dehydroepiandrosterone sulphate (DHEAS) and the sex hormone-binding globulin (SHBG) capacity were similar in males and females. Multivariate regression analysis showed that the inhibin concentration in males correlated with the testosterone concentration and in females it correlated not only with testosterone concentration but also with gestational age at delivery and SHBG capacity (all p < 0.001). Inhibin concentrations in cord arterial serum in a subgroup of 24 males and 31 females were higher than in the venous serum in both sexes but the differences were not statistically significant. Concentrations of DHEAS determined in 22 female cord arterial blood samples (6.0 ± 2.5 μmol/l) were significantly higher than the venous concentrations (5.2 ± 1.8 μmol/l) (p < 0.05). Inhibin did not correlate with DHEAS either in their arterial serum concentrations or in the arteriovenous concentration differences. The findings of this study are consistent with the placenta being the principal source of inhibin circulating in the human fetus in late pregnancy. Further, they suggest that there are minor sex differences in placental metabolism of inhibin and the steroidal sex hormones.

Exploring the Underlying Hormonal Mechanisms of Prenatal Risk Factors for Breast Cancer: A Review and Commentary

“…Whether birth size is associated with maternal estradiol, however, is unclear (38,(41)(42)(43). In the cord, birth weight is not associated with estradiol (38,42,44,45), estrone (38,44), or androgens (38,45), and the association with estriol is unclear (38,42). Overall, the data imply that birth weight is positively associated with maternal but not fetal estrogen concentrations.…”

“…One study showed no association with DHEA, DHEA sulfate, androstenedione, and testosterone measured at the end of pregnancy (38); however, another larger study found higher maternal testosterone levels at weeks 17 and 33 in the lower-birthweight babies (65). In the cord, birth weight was not associated with androgens in two studies (38,45). Thus, there is little evidence that birth weight is positively correlated with maternal or cord androgens, although additional studies are necessary.…”

Maternal, prenatal and perinatal characteristics and first trimester maternal serum hormone concentrations

“…Our data show no association of birth weight with first trimester estrogens seeming to suggest that if oestrogen explains the association of birth weight and breast cancer risk, the critical exposure window may be later in pregnancy. Yet associations of birth weight with cord estrogens are unclear (Simmons et al, 1994;Shibata et al, 2002;Troisi et al, 2003;Nagata et al, 2006), and breast cancer risk in women prenatally exposed to diethylstilbestrol does not differ by trimester of first exposure (Palmer et al, 2006). Other prenatal factors could act differently.…”

Perinatal imprinting by estrogen and adult prostate disease

“…Because testosterone is the natural substrate in estrogen biosynthesis and the responsible enzyme (CYP19͞aromatase) is expressed by the prostate (10), it is plausible that estrogen can be produced locally within the prostatic tissue in the newborn period. Second, in late prenatal and early postnatal boys, circulating levels of estrogen are high, reaching equal or higher levels than in girls (8). Third, in the present and previous work (2,11), it was demonstrated that the steroid 5␣-androstane-3␤, 17␤-diol (3␤ A-diol), a metabolite of dihydrotestosterone (DHT) with estrogenic properties, could serve as a mitogen in the prostate in the neonatal period acting through ER␣.…”

“…Interestingly, several such ways of exposure seem to exist. First, infant boys show physiologically high levels of testosterone because of a postnatal reproductive hormone surge at the age of 1-3 months, sometimes referred to as ''baby puberty'' (8,9). Because testosterone is the natural substrate in estrogen biosynthesis and the responsible enzyme (CYP19͞aromatase) is expressed by the prostate (10), it is plausible that estrogen can be produced locally within the prostatic tissue in the newborn period.…”