Toru Tabei

Serum levels of inhibin in maternal and umbilical blood during pregnancy

Inhibin levels were measured by a double antibody heterologous radioimmunoassay in the peripheral serum of 75 pregnant women throughout gestation and in serum from the umbilical vein and artery, which was obtained at the time of delivery. For reference, samples were obtained from 20 nonpregnant women in the early (days 0 to 3), mid (days 4 to 8), and late (days 9 to 14) luteal or follicular phase. Maternal serum levels of inhibin (mean +/- SEM) in early (6 to 12 weeks) gestation (36.4 +/- 2.6 U/ml, n = 36) were significantly (p less than 0.01) higher than those in serum from nonpregnant women in the mid (23.9 +/- 2.5 U/ml, n = 19) or late (11.3 +/- 0.6 U/ml, n = 19) luteal phase. Inhibin levels in maternal serum fell to 15.9 +/- 1.4 U/ml (n = 24) in mid (14 to 20 weeks) gestation and then gradually increased during late (21 to 40 weeks) gestation to peak levels of 49.4 +/- 5.1 U/ml (n = 9) at 36 to 37 weeks. Inhibin levels declined in parallel with human chorionic gonadotropin concentrations during the first trimester (r = 0.587 at p less than 0.01). Significant positive correlations (p less than 0.001) were observed between serum levels of inhibin and 17 beta-estradiol (r = 0.560), progesterone (r = 0.648), and human placental lactogen (r = 0.715) during mid and late (20 to 40 weeks) gestation. Inhibin levels in umbilical vein serum (38.5 +/- 1.3 U/ml, n = 5) were not different from those in umbilical artery serum (39.4 +/- 3.6 U/ml) but were significantly (p less than 0.01) lower than those in maternal serum (50.9 +/- 5.3 U/ml), which was obtained at the time of delivery. By day 5 of puerperium, serum levels of inhibin in the maternal vein were extremely low (2.3 +/- 0.1 U/ml, n = 7); these levels were nearly one fifth lower than follicular phase levels of 10.9 +/- 3.4 U/ml (n = 38). We propose that maternal inhibin in early gestation is secreted from the corpus luteum of pregnancy but that increasing inhibin levels during mid and late gestation result from inhibin that is produced by the placenta. The lack of an umbilical arterial-venous gradient for inhibin and the higher levels of inhibin in maternal serum argue against a fetal source of inhibin in the maternal circulation. The physiologic function of inhibin that is produced by the corpus luteum and by the placenta remains to be determined.

Sex steroid binding protein (SBP) in dog plasma

A specific sex steroid-binding protein (SBP) is demonstrated in the plasma of mongrel dogs. For mature females (5 yrs old) the equilibrium constants of association Ka) at 4° are 1.44 ± 0.26 × 108 M−1 for 5α-dihydrotestosterone (DHT)∥, 4.20 ± 2.90 × 1 07 M−1 for testosterone (T), and 7.72 ± 5.29 × 106 M−1 for oestradiol-17β (E2). For mature males, the Ka for DHT is 1.22 ± 0.34 × 108 M−1. Elefctrophore in 5%, polyacrylamide gels containing [3H]-DHT showed the presence of an active molecular species with RF 0.32. Dehydroepiandrosterone. oestrone, androstenedione, progesterone, and cortisol do not significantly compete with DHT for the steroid binding site. The rate constant of DHT dissociation at 4°C is 0.009s−1 (t12 = 77s)f. The concentration of SBP (μg DHT bound/100 ml plasma. mean ± S.D.) in mature females (9.0 ± 1.3) is significantly higher (P < 0.01) than in mature males (6.2 ± 0.8). No sex difference was observed in immature dogs, the values are in the range of mature females (8.7 ± 1.4 for males and 8.2 ± 0.4 for females). The results indicate that the dog should be a valuable animal model for studying the physiological rote of SBP.

Differentiation of sex steroid-binding protein in adult rhesus monkeys☆☆☆★

Several species of primates have sex differences in sex steroid-binding protein (SBP), female adults having higher serum binding capacities (micrograms of dihydrotestosterone bound per deciliter) than male adults, e.g., male humans, 1.28 +/- 0.4; human females, 2.86 +4- 0.9; Macaca nemestrina male animals, 5.62 +/- 1.24; Macaca nemestrina female animals, 11.07 +/- 1.85 (means +/- standard deviations). SBP correlates inversely with metabolic clearance rates of testosterone (T). The sex difference was identified in rhesus monkeys, six per group, evaluated 4 years after postpubertal castration: male animals 3.95 +/- 1.14; female animals 5.85 +/- 0.98 (p less than 0.05). Estradiol-17 beta (E2) pellets producing physiologic levels of E2 in female monkeys obliterated the sex difference by increasing SBP in male animals. After withdrawal of E2, physiologic levels of T in male monkeys produced a marked decrease in SBP levels (p less than 0.01), and the sex difference reappeared; castrated female animals and prenatally androgenized female animals responded similarly to T (2.81 +/- 0.81 and 2.64 +/- 0.49, respectively). Both values were greater (p less than 0.05) than that of the male group (2.02 +/- 0.33). These data suggest that the sex steroid milieu influences the binding capacity of SBP for potent androgens in adulthood but that the differentiation of the SBP sex in rhesus monkeys is determined by factors other than prenatal androgen exposure.

Peripheral control of hormone metabolism

Abstract The presence of 5α-reductase and 20α-hydroxysteroid dehydrogenase has been demonstrated in brain from two species (rat and baboon). Under the conditions of the present experimental design, there appear to be significant differences related to sex and species but not to age. Our data, supported by observations of others, suggest a regulatory role of these enzymes in the control of feedback mechanisms.

Neonatal Differentiation of Hepatic DHA 16α- and 7α-Hydroxylases

The postpubertal sex differences in rats, for the hepatic mixed function oxidation of many steroids and drugs, are gonad-dependent in males. Hepatic microsomes of males castrated as neonates had DHA 1