John D. Townsley

Evaluation of placental steroid 3-sulfatase and aromatase activities as regulators of estrogen production in human pregnancy.

Abstract The importance of variations in the activity of placental steroidogenic enzymes in regulating estrogen production has been investigated. Maternal estrogen excretion during the final week of gestation and placental aromatase and steroid 3-sulfatase activities were determined in a series of 22 normal and 39 complicated pregnancies. There were no significant correlations between estrogen excretion and enzyme activities. The data do not confirm previous reports that placental aromatizing capacity is reduced in diabetes and toxemia. It is concluded that variations in these enzyme activities, as determined in vitro, are largely independent of maternal disease and do not provide a general mechanism for regulation of estrogen production.

Serum cortisol levels affect the metabolic clearance rate of progesterone in female baboons

Since interactions between progesterone (P4), Cortisol (F), cortisone (E) and corticosteroid binding globulin (CBG) may influence the metabolic clearance rates (MCR) of these steroids, the effect of altering circulating F concentrations on clearance of the steroids was determined. MCR of P4, F and E were determined by the iv constant infusion method in 6 pregnant and 6 nonpregnant baboons (Papio papio). Serum F concentrations were altered by iv infusion of 5 mg F/90 min or im injection of betamethasone (3 mg bi-daily for 2 days). Mean MCR-P4 (1/d/kg ± SE) was greater (P < 0.01) in pregnant (92.8 ± 8.5) than in nonpregnant (53.9 ± 4.4) animals while mean MCR-F was similar in both groups (10.8 ± 1.2 vs 13.0 ± 1.5, respectively). Mean MCR-E was also similar in pregnant (30.8 ± 4.9) and nonpregnant (34.1 ± 4.5) baboons. Mean serum F concentrations (/gmg/100 ml ± SE) in 4 nonpregnant (42.0 ± 8.6) and 4 pregnant (52.2 ± 10.0) baboons were increased (P < 0.05) 60% by F administration but MCR-P4, -F and -E were unaltered. Betamethasone treatment reduced (P < 0.05) serum F 75% in both groups. In nonpregnant baboons, betamethasone treatment reduced (P < 0.01) MCR-P4 (37.3 ± 3.9), MCR-F (7.4 ± 1.6) and MCR-E (18.5 ± 3.7). Betamethasone treatment of pregnant animals reduced (P < 0.01) MCR-P4 (56.5 ± 7.4), MCR-F (6.3 ± 0.8) and MCR-E (14.6 ± 2.6). Infusion of F into betamethasone-treated animals increased serum F levels and increased MCR-P4, -F and -E. It is concluded that variations in serum F levels affect the clearance of F, E and P4 presumably because of the mutual interactions of these steroids with CBG.

Maternal serum 17 β-estradiol levels in normal and complicated pregnancies: A comparison with other estrogen indices of fetal health

Abstract Maternal serum 17β-estradiol (SE 2 ) levels are dependent to a significant extent on fetoplacental interaction, suggesting that SE 2 levels could be used as an index of fetoplacental well-being. A comparative study of SE 2 levels with our previously reported serum estriol (SE 3 ), 24 hour urinary estrogens (UE), and urinary estrogen/creatinine (E/C) ratio determinations in normal and complicated pregnancies was undertaken. The normal SE 2 range for the last 10 weeks of pregnancy was established with the use of serial samples from 20 uncomplicated pregnancies. Significant correlations (p 2 and UE (r = 0.29), SE 2 and E/C (r = 0.32), but not between SE 2 and SE 3 (r = 0.06). SE 2 levels in serial samples from 31 complicated pregnancies (e.g., diabetes, toxemia, postmaturity, anencephaly) were determined. SE 2 patterns paralleled other estrogen parameters in 7 of 8 patients when SE 3 , E/C, and UE were low and were compatible with our assessment of fetoplacentai status in 9 of 10 patients where SE 3 and E/C conflicted. However, SE 2 was low in 7 of 13 patients whose SE 3 , E/C, and UE were normal and who were delivered of normal infants (5) or infants (2) whose compromise was not predictable by assay of estrogen levels. It is concluded that the high incidence (26 per cent) of misleading low SE 2 patterns in complicated pregnancies with normal fetal outcome limits the value of this index. Serial UE, E/C, total creatinine excretion, and 24 hour urine volume currently provide the most reliable data to monitor estrogen metabolism as one parameter of fetoplacental well-being.

Catabolic regulation of blood cortisol in premature and term baboon neonates.

The metabolism of I.V. administered 4-[14C]-cortisol (F) was examined in 3 premature (cesarean section at 160, 167, and 174 days gestation, term = 184 days) and 8 spontaneously delivered term (184 ± 2 days) baboon neonates (Papio papio). Three premature (Group 1) and 4 spontaneously delivered animals (Group 2) were studied 2–18 h after delivery and, the remainder on the 5th (N = 2) or 12th (N = 2) day of life (Group 3). [14C]-Metabolites were isolated by ehromatography and crystallization. More than 10% of 14C was in liver, 3–9% in intestine and brain, ≤ 2% in lung, kidney, heart, spleen, and urine, and < 0.2%/g in blood and muscle 30 min. after injection. Most 14C (77.5 ± 1.6%) in all tissues was unconjugated. Extrahepatic tissues were primarily responsible for oxidation of F to cortisone. Formation of tetrahydrocortisol (THF), tetrahydrocortisone (THE), two hydroxylated metabolites and glucuronoside conjugates was restricted to liver. Alterations in F metabolism (decreased hydroxylated metabolites, increased THF and THE glucuronides) were not evident until 5–12 days after delivery. It is concluded that extrahepatic 11β-hydroxysteroid dehydrogenase is important in achieving a low F:E ratio in fetal blood. The similarity in F catabolic patterns of premature and day 1 term newborns makes it unlikely that changes in metabolism can account for the increased fetal blood F concentrations prior to parturition.