Androgens in the Fetal Guinea-Pig After Maternal Infusion of Radioactive Testosterone

Abstract

Testosterone was measured in plasma pools from male and female fetal guinea-pigs between the ages of 30 and 55 days of pregnancy. Between days 33 and 36 the testosterone concentration in the plasma of males (1.4 ng/ml) was several times higher than that found at other ages or that measured in female fetuses. After infusion of tritiated testosterone for 2 h into pregnant guinea-pigs at day 36 of pregnancy, high levels of testosterone and androstenedione were found in maternal plasma. Nevertheless, tritiated testosterone and androstenedione could hardly be shown in the fetuses. Similar large differences in plasma progesterone levels appeared to exist between the maternal and the fetal circulation. Therefore, only a very small fraction of these steroids can penetrate from the maternal circulation into that of the fetus. This finding might be explained by the large difference in androgen-binding capacity between maternal and fetal plasma, as was shown by equilibrium dialysis.

Differential Effects of Maternal Stress on Circulating Levels of Corticosterone, Progesterone, and Testosterone in Male and Female Rat Fetuses and Their Mothers*

“…This is in contrast to similarities in absolute levels of progesterone and the consistent correlations found in male and female littermates. As has been shown in guinea pigs (31), this steroid does not equilibrate across maternal and fetal circulations.…”

Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport

“…Unlike rats, human and sheep placentae have aromatase enzyme that effectively metabolizes androgens to estrogens preventing fetal exposure [22,25]. Similar findings of a lack of increase in fetal testosterone levels, despite an increase in maternal testosterone levels, is reported in pregnant rats [27], guinea pigs [44], and sheep [22]. There are no reports on the fetal testosterone levels in human IUGR and preeclamptic pregnancies, however a 20-fold increase in maternal testosterone levels is not associated with changes in testosterone levels in cord venous blood [48].…”

“…Testosterone is a lipophilic hormone and is suggested to diffuse across tissues including placenta [24-26]; however increase in maternal plasma testosterone concentration, that caused fetal growth inhibition, was not associated with increase in fetal body testosterone concentration or alteration in AGD (functional indicator of androgenicity). This finding may indicate that testosterone administered to the dam is not delivered to the fetus, but is metabolized or blocked at the placenta [27,44]. Rat placenta does not have aromatase enzyme [45,46] to convert testosterone to estradiol but predominately expresses Δ 4 -reductase and 17β-hydroxysteroid dehydrogenase that metabolizes testosterone to weak androgens such as 5α-androstane-3α-17β-diol [47] and androsterone [27], respectively.…”

Virilization during Pregnancy due to Bilateral Hyperthecosis

“…If the mother becomes virilized, 65% of female in fants present symptoms of masculinization as well [15]. Aromatization of androgens in the placenta is generally very efficient [5] and the transfer of androgens to the fetus low [ 18]. In our case the ST level in the newborn was normal [1] and higher in the umbilical artery than in the umbilical vein.…”