Catechol estrogen concentrations in maternal and umbilical circulation at different modes of delivery.

To investigate the role of catechol estrogens in human parturition, these steroids were analyzed in samples from the maternal venous and umbilical venous and arterial plasma at vaginal (n = 28) and abdominal (n = 28) delivery. To ensure the appropriateness of collection of umbilical artery and venous blood samples, progesterone content was also determined. Although there is no significant difference in maternal vein content of catechol estrogens between the two groups, the umbilical venous (p = 0.03) and arterial (p = 0.002) plasma concentrations are significantly higher at vaginal delivery than those measured at abdominal delivery. In view of the present data and the importance of catechol estrogens in prostaglandin synthesis and in potentiating the activity of catecholamines through competitive inhibition of catechol-O-methyltransferase, it is suggested that catechol estrogens may play a role in triggering the events involved in the onset of labor and delivery in humans.

The absence of a catechol estrogen effect on blood pressure in the male rat.

Since catechol estrogens are potent competitive inhibitors of catechol-O-methyl transferase (COMT), it has been suggested that they may prolong the half-life of catecholamines which in turn can cause hypertension. Thus, experiments were carried out to study the effect of catechol estrogens on blood pressure in the male rat following chronic administration. Results demonstrate that 2-hydroxyesterone (2,3-dihydroxyestra-1,3,5(10)-trien-17-one) and 2-hydroxy-estradiol (estra-1,3,5(10)-triene-2,3,17 beta-triol) even when administered in high doses do not alter blood pressure.

Urinary catechol estrogens in cycles stimulated by human menopausal gonadotropin.

Catechol estrogens, estrogen metabolites of potential physiologic significance, were measured in infertile women undergoing ovulation induction with human menopausal gonadotropins. Urinary 2-hydroxyestrone (2-OH-E1) specimens were obtained from 12 women in one or more stimulated cycles. The actual time for the administration of human chorionic gonadotropin to induce ovulation was based on serial plasma estradiol (E2) specimens. A significant correlation between plasma E2 and urinary 2-OH-E1 was demonstrated, similar but more pronounced than that seen in normal cycling women. This confirms previous work that showed that 2-OH-E1 is the major urinary estrogen metabolite in the nonpregnant state and further suggests that urinary catechol estrogens are a useful index of ovarian function.

Radioimmunoassay of 2-hydroxyestrone in plasma during the estrous cycle of the rat: interrelationships with estradiol, progesterone, and the gonadotropins.

A RIA for 2-hydroxyestrone (2-OHE1) in rat plasma has been developed. The assay employs an antiserum that is specific for catechol estrogens. Specificity is further ensured by purification of plasma extracts on Sephadex LH-20 columns before RIA. Blood was collected at 0 C in the presence of ascorbic acid to prevent oxidation. Under these conditions, the conversion of 2-OHE1 to methylated derivatives was found to be negligible. Plasma 2-OHE1, LH, FSH, PRL, estradiol, and progesterone were measured at 3-h intervals throughout the 4-day estrous cycle of the rat. The 2-OHE1 concentration varied from undetectable to 11 pg/ml plasma. No clearly defined relationship with the other hormones analyzed was observed. Thus, it is unlikely that changes in circulating 2-OHE1 levels are involved in the regulation of the gonadotropin surge and ovulation.

DNA binding studies of 7-bulky-substituted actinomycin analogues.

The DNA binding properties of several 7-substituted aralkylaminoactinomycin D analogues have been studied by spectrophotometry, DNA melting temperature studies, DNA-drug dissociation studies, and circular dichroism. Despite the presence of such bulky groups as 2-pyrrolylmethylamino or 3,4-dichlorobenzylamino at the 7 position, these analogues bind to DNA, inhibit RNA synthesis, and exhibit antitumor activity. A model is proposed for the interaction of the pyrrolyl analogue with phosphate groups of the DNA binding site, explaining the increased binding affinity for DNA of this actinomycin D analogue.

Structural and electronic effects resulting from metal-flavin ligation.

The synthesis and physical properties of a model metalloflavin complex, [(10-methylisoalloxazine)-(NH3)4Ru](PF6)2 . 2H2O are reported. The structure of this stable, enantiomeric compound was elucidated by x-ray diffraction methods with a final unweighted R value of 0.054. Crystals belong to the triclinic space group P1 with unit cell dimensions: a = 9.631, b = 10.618, c = 13.216 A; alpha = 113.86, beta = 100.19, gamma = 94.12 degrees. Chelation of the metal ion to the flavin occurs at the N(5) and O(4) positions, with a short Ru-N(5) bond distance of 1.979 A. Steric and electronic factors induce a 9.9 degrees bend in the isoalloxazine ring system and a significant lengthening of the C(4a)-N(5) bond. The flavin absorption bands shift significantly toward lower energy on complexation and a new band occurs at 617 nm. These absorptions are pH-dependent and pK alpha values for the complex are 0.6 and 7.4. The spectra of this complex exhibit similarities to that of metallosemiquinone species and arguments are made that a significant amount of electron density is donated to the pi-system of the flavin. Proton NMR studies suggest enhanced electron density at the N(10) position, probably occurring through backbonding interactions. Cyclic voltametry studies are also consistent with substantial metal to ligand pi-electron donation, since it is significantly more difficult to reduce the coordinated flavin relative to the free ligand under the same conditions. Moreover, the complexed flavin accepts electrons in 1-electron rather than 2-electron steps. Spectroelectrochemical studies on the 1-electron reduced complex indicate a similarity with other M(II)-F1 species.