Marjorie V. Frankland

On the regulation of estrogen production by cortisol and ACTH in human pregnancy at term: Memorial foundation award thesis☆

Abstract Maternal and fetal adrenals provide precursors for placental estrogens. Mechanisms of adrenal control were studied in patients undergoing elective cesarean section at term. Ten patients served as controls; six received 150 mg. of cortisol intravenously and 13 received 40 I.U. of Depo-ACTH intramuscularly. Maternal venous and cord venous and arterial plasma were analyzed for ACTH, total and unbound unconjugated cortisol, DHEA and DHEA sulfate, estrone, estradiol, and estriol. Cortisol increased maternal and—after placental transfer—fetal cortisol and subsequently estrogen precursors, and estrogens in mother and fetus. ACTH first appears to increase estrogens; four to seven hours after its injection, estrone and estradiol normalize while estriol decreases to subnormal values in mother and fetus. Interpretation of these findings is given. The data further support the hypothesis that ACTH is a regulating hormone for the fetal adrenal, although no evidence was obtained to substantiate transfer of ACTH from mother to fetus.

Neutral C19-steroids and steroid sulfates in human pregnancy II. Dehydroepiandrosterone sulfate, 16α-hydroxydehydroepi-androsterone, and 16α-hydroxydehydroepiandrosterone sulfate in maternal and fetal blood of pregnancies with anenphalic and normal fetuses

Abstract Dehydroepiandrosterone sulfate (DS), 16α-hydroxydehydroepiandrosterone sulfate (16α-OH-DS) and 16α-hydroxydehydroepiandrosterone (16α-OH-D) were measured in cord plasma of five anencephalic fetuses with histologically proven hypoplasia of the fetal zone of the adrenal cortex. DS was determined by the Zimmermann reaction on paper as described previously by us, the 16α-hydroxylated compounds by a modification of the method of Katz. These hormones were also measured in antecubital venous blood of the mothers of these fetuses. For comparison normal pregnant women and normal fetuses were studied. Neither 16α-OH-D nor 16α-OH-DS could be detected in peripheral blood of mothers bearing anencephalic or normal fetuses. In the former group, all DS levels (M±s = 93±31 μg%) were within the normal range. 16α-OH-D, 16α-OH-DS, or DS could not be detected in the cord plasm of anencephalic fetuses. If these steroids were present, their concentrations (

Neutral C19-steroids and steroid sulfates in human pregnancy II. Dehydroepiandrosterone sulfate, 16α-hydroxyderhydroepiandrosterone, and 16α-hydrosydehydroepiandrosterone sulfate in cord blood and blood of pregnant women with and without treatment with corticoids

Dehydroepiandrosterone sulfate (DS), 16α-hydroxydehydroepiandrosterone sulfate (16α-OH-DS) and 16α-hydroxydehydroepiandrosterone (16α-OH-D) were measured in mixed cord plasma and maternal plasma of 6 pregnant women who were treated with prednisone and hydrocortisone succinate during pregnancy and labor. All three steroid hormones were markedly lowered in the fetal blood. (DS: M = 53 μ%, 16α-OH-DS: M = 45 μg%, 16α-OH-D = < 6 μg%). The level of these steroids appears to vary inversely with the amount of corticoids given to the mother. In the maternal blood DS was either not measurable or very low (range < 8–29 μg%) as compared with normal values for untreated pregnant women. No 16α-OH-D or 16α-OH-DS could be detected in the p lasma of these patients. Maternal urinary estriol, estrone, and estradiol were also decreased in three of the cases studied. It is hypothesized that the decrease of urinary estrogens in these patients is mainly due to a suppression of the release of C19-steroid hormones by the maternal and fetal adrenal; the suppression of the fetal adrenal by exogenous corticoids being of major importance. It is pointed out that in cases with corticoid treatment during pregnency a low urinary estrogen excretion does not need to interfere with the development of pregnancy and does not reflect a hazard to the fetus.

On the regulation of fetal and maternal 16α-hydroxydehydroepiandrosterone and its sulfate by cortisol and ACTH in human pregnancy at term

In studying the mechanisms which govern estriol production in human pregnancy at term, 16 alpha OH-DHEA, 16alpha-OH-DHEA sulfate, and unbound unconjugated cortisol were measured in peripheral venous plasma of 28 healthy women and in cord venous and arterial plasms of their newborn infants at the time of elective cesarean section prior to the onset of labor. In eight cases treated with 150 mg. of cortisol, maternal and cord plasma 16alpha-OH-DHEA and its sulfate were considerably lower than in 10 control cases. Approximately 4 to 8 1/2 hours after injection of 40 I.U. of Depot-ACTH, both of these estriol precursors were also significantly decreased. It is concluded from these experiments that cortisol causes a decrease of estriol mainly by suppressing fetal 16alpha-OH-DS.

Neutral C19-steroids and steroid sulfates in human pregnancy: VI. Quantification of plasma testosterone in cord venous blood

Abstract Plasma testosterone was quantitated in cord venous blood of 40 normal newborns of primiparous women delivered vaginally at term. The method consisted of purification by thin layer, paper and column chromatography and measurement by competitive binding assay utilizing sex steroid binding protein (BSP) of maternal plasma obtained in late pregnancy. Values were corrected for blank (if necessary) and recovery of the internal standard. Mean and standard deviation were 22 ± 14 ng % plasma. No difference was found between female and male newborns. Reasons for the considerably higher values of other investigators are discussed.

Neutral C19-steroids and steroid sulfates in human pregnancy IV. Isolation and identification of unconjugated dehydroepiandrosterone and 16α-hydroxydehydroepiandrosterone from pooled cord blood

Abstract Identification of unconjugated dehydroepiandrosterone (D) and 16α-hydroxydehydroepiandrosterone (16α-OH-D) isolated from 500 ml of cord plasma obtained from mixed arterial and venous cord blood collected after vaginal delivery at term is presented. The identification is based upon in vitro placental conversion of D and 16α-OH-D to 17β-estradiol and estriol respectively, further on formation of D acetate and 16α-OH-D diacetate and their thiosemicarbazones, and finally on reduction of the acetates and repeat acetylation. All acetates were doubly labelled and chromatographed to constant 3 H/ 14 C ratios. Constant ratios were also obtained in recrystallizations of D acetate and 16α-OH-D diacetate after reversed isotope dilution.

Unbound Unconjugated Cortisol in Umbilical Cord and Corresponding Maternal Plasma

Unbound unconjugated cortisol was measured in cord venous and arterial plasma and in simultaneously obtained maternal venous plasma by equilibrium dialysis at 37 and 5 °C and by centrifugal ultrafiltration at 37 °C. Total cortisol was quantitated by a specific method based on chromatography and competitive protein binding. 67 cases were studied at cesarean section, 7 at vaginal delivery. Regardless of the method used, values of unbound cortisol in cord plasma were found to be much lower than previously reported. The values for unbound cortisol in the mothers exceed approximately 3-fold those in the newborn.

Neutral C19-steroids and steroid sulfates in human pregnancy: VII. Plasma testosterone in maternal peripheral blood and in cord venous blood after administration of testosterone enanthate to the mother

Abstract 20 normal primipara at term received testosterone enanthate and estradiol valerate (Deladumone OB R ) intramuscularly for lactation suppression. The injections were given at various stages of labor, thus the time intervals between administration of the drug and blood sampling at delivery varied from 12 to 655 minutes. Although unconjugated plasma testosterone (measured by competitive binding assay) increased more than 20 fold in maternal blood, no such increase was observed in cord venous blood of the female and male newborns. This was confirmed in a patient undergoing elective cesarean section and in pooled plasma from 6 additional normal cases. Testosterone enanthate was not detectable in this pool, nor in 12 individual samples. After injection of the drug, cord plasma androstenedione was found to be slightly elevated in one case and normal in the six others studied. It is concluded from these studies that at term a time-limited, but large increase of maternal plasma testosterone does not cause an increase in fetal testosterone. A conversion to androstenedione within the fetus is ruled out as a possible factor to explain these findings. Withholding of testosterone by the sex steroid binding protein of maternal blood and in particular, aromatization of testosterone to estradiol and estrone in the placenta may be the controlling factors.

Neutral C19-steroids and steroid sulfates in human pregnancy V. Isolation and identification of unconjugated testosterone and androstenedione from pooled cord blood

Abstract Unconjugated testosterone (T) and androstenedione were isolated from cord plasma obtained from mixed arterial and venous cord blood collected after vaginal deliveries at term. The identification of both hormones is based upon double labelled derivative formation and reverse isotope dilution. Only the latter procedure gave constant 3 H 14 C ratios for the acetate of testosterone. Androstenedione was also biotransformed to 17β-estradiol. The same procedures did not provide sufficient proof for the existence of 16α-hydroxyandrostenedione and 16α-hydroxytestosterone in cord blood. Tentative evidence for their being present is given.

Serotonin concentration in the spleen

SummaryModifications of previous methods for determining the serotonin concentration of blood and other body tissues are described.The spleen does not appear to release free serotonin into the portal blood. On the contrary, it appears that serotonin is removed from the blood by the spleen. Diseased spleens from human beings and rats have an abnormally low serotonin concentration which is not dependent upon the blood platelet concentration.An unidentified substance, probably chemically related to serotonin, was found spectrophotofluorometrically in 3 human spleens.