I. John Davies

Danazol Inhibits Steroidogenesis

Danazol was found to inhibit multiple enzymes of steroidogenesis directly in the pregnant mare serum (PMS)-treated hamster ovary and the rat testis and adrenal in vitro. In the PMS-treated hamster ovary, danazol inhibited 17alpha-hydroxylase, 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase. In the rat testis, danazol inhibited 17alpha-hydroxylase, 17,20-lyase, 3beta-hydroxysteroid dehydrogenase, and 17beta-hydroxysteroid dehydrogenase. In the rat adrenal, danazol inhibited 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11beta-hydroxylase. Two hours after a subcutaneous injection of 5 mg/kg of danazol to adult male rats, serum luteinizing hormone levels were significantly increased and serum testosterone levels were significantly suppressed. These findings suggest that in the rodent one of danazols major pharmacologic effects is the direct inhibition of steroidogenesis.

Estradiol receptors in the pituitary and anterior hypothalamus of the rat: measurement by agar gel electrophoresis.

The reliability of agar gel electrophoresis in the measurement of high-affinity saturable estrogen-binding component in the cytosol of the rat pituitary gland and anterior hypothalamus was assessed. The available binding sites were determined in small samples with good precision and accuracy. Incubation with 100-fold competitor was more satisfactory than heat-treatment for measuring nonspecific binding. There was substantial, but incomplete, dissociation of albumin-estradiol complexes. The total number of estrogen binding sites in the anterior hypothalamus was approximately 15% greater in 28-day-old females than males (p .02). However, differences in the number of binding sites in the pituitary was not significant (p .02). The pituitary was found to contain twice as many binding sites as the anterior hypothalamus in both sexes. The latter finding is consistent with the importance of the direct action of estrogen on the pituitary in mediating pituitary function.

The relationship between progesterone and prostaglandin f concentrations in the plasma of pregnant rabbits

Abstract The concentrations of progesterone and PGF have been measured in the peripheral plasma of 7 rabbits during pregnancy. The mean concentration of progesterone reached a maximal value on day 13 post coitum (p.c.), declined gradually until day 29 p.c., and then fell more sharply between days 29–32 p.c., before delivery on day 32. The mean concentration of PGF was less than 300 pg/ml for much of pregnancy but showed a significant increase between days 21 and 30 p.c. In 5 out of 7 animals, the rise in PGF during late pregnancy occurred prior to or coincident with the preparturient decline in progesterone.

Palmitic/stearic ratio of amniotic fluid in diabetic and nondiabetic pregnancies and its relationship to development of respiratory distress syndrome

Abstract Amniotic fluid (AF) samples obtained from 64 patients within 72 hours of delivery of their infants were analyzed by gas-liquid chromatography to quantitate the individual fatty acids present in the hydrolysate of the lecithin fraction. The results were expressed as the palmitic/stearic (P/S) ratio, which we have considered to be a reflection of the relative amount of dipalmityl lecithin being secreted into the AF from the fetal lungs. Of the 64 patients studied, 31 were insulin-dependent diabetic patients and 33 were nondiabetic. Of the 31 infants of the diabetic mothers, eight developed the respiratory distress syndrome (RDS). Of the 33 infants of the nondiabetic mothers, seven developed RDS. In both the diabetic group and the nondiabetic group, each considered separately, the mean P/S ratio distinguished RDS from non-RDS patients (p

Prostaglandin F in the peripheral plasma of the rhesus monkey in normal pregnancy and after the administration of dexamethasone and PGF2α

The concentration of prostaglandin F (PGF) has been measured in the peripheral plasma of normal rhesus monkeys (Macaca mulatta) during the final third of gestation, and in monkeys treated with dexamethasone or PGF2α after day 145 of pregnancy. Daily administration of PGF2α (10–15 mg/day im) reliably induced abortion within 3–6 days. However, dexamethasone (8 mg/day im from day 145) had no effect on the length of gestation. The concentration of PGF in the femoral venous plasma of untreated or dexamethasone-treated monkeys was highly variable, both in serial samples taken from the same animal and in samples taken from different animals at the same time of gestation. There was no indication of an effect of dexamethasone treatment on the plasma PGF levels, nor did the concentration of PGF increase during late pregnancy before spontaneous parturition. These results show that the myometrium of the pregnant rhesus monkey is highly sensitive to exogenous PGF2α during late gestation. However, a significant increase in the peripheral plasma concentration of PGF prior to the onset of labor was not observed.

THE AFFINITY OF CATECHOL ESTROGENS FOR ESTROGEN RECEPTORS IN THE PITUITARY AND ANTERIOR HYPOTHALAMUS OF THE RAT

The purpose of these experiments was to evaluate the potential for interaction between 2-hydroxyestrone and 2-hydroxyestradiol and estrogen receptors in rat pituitary and anterior hypothalamus. The 150,000 X g supernatant fractions of these tissues were prepared, the estrogen receptor-site concentration was measured, and the relative abilities of unlabelled estradiol, estrone, 2-hydroxyestradiol and 2-hydroxyestrone to compete with [3H]estradiol for estrogen binding sites was determined. From these results, and the previously determined association constant for [3H]estradiol, 10(10)M-1, the association constants of the other estrogens were calculated. The introduction of the 2-hydroxy group caused only a modest reduction in the affinity of these estrogens for the receptors. The association constants of the 2-hydroxy derivatives were within one order of magnitude of those of the parent compounds. These results demonstrate the potential for interaction between catechol estrogens and estrogen receptor in rat brain and pituitary of a magnitude which could be biologically significant.