Isadore G. Ances

The metabolic clearance rate, blood production, interconversion and transplacental passage of cortisol and cortisone in pregnancy near term.

Extract: A constant infusion of 14C-cortisol and 3H-cortisone for 4 hr was given to six pregnant women, at term, at the time of elective cesarean section. Radioactive and nonradioactive cortisol (F) and cortisone (E) concentrations were determined in maternal and cord plasma at the time when the concentration of the radioactive steroids had reached a plateau. Metabolic clearance rates (MCR), plasma levels of endogenous F and E, blood production rates (BP), conversion ratios (Cr), and transfer constants ([ρ]BB values) were calculated and compared with those obtained in eight nonpregnant women, half of whom took contraceptive medication (subjects taking “the pill”) and half of whom did not (control subjects).The MCR (F) of women near term, control subjects, and women receiving contraceptive treatment were (mean ± sd) 133 ± 47, 141 ± 37, and 62 ± 24 liters/24 hr, respectively. The latter was significantly lower than the other two. The MCR (E) were similar in all three groups of subjects and 4–7 times greater than MCR (F).The ratio of the endogenous F/E for control subjects was significantly lower (4.8 ± 0.6) than that for women on the pill (9.0 ± 1.6) or for pregnant women (7.5 ± 1.7). In contrast to their mothers, the neonates had an F/E ratio of 0.85 ± 0.34 with a mother/cord ratio for F of 4.9 ± 2.5 and for E of 0.50 ± 0.15.In eight fetuses of 3–6 months of gestational age, plasma concentrations of F (2.1 ± 1.2 μUg/100 ml) and E (4.7 ± 3.3 μUg/100 ml) were lower than those of six neonates (6.3 ± 2.9 for F and 7.2 ± 1.2 μUg/100 ml for E).For control subjects, the CrF→E was significantly higher and the CrE→F significantly lower than these ratios for pregnant women and for women on contraceptive medication. From the values of BP (F) for each subject and the corresponding transfer constant [ρ]BBF→E it was estimated that all the BP (E) for the subjects studied arose from BP (F), which suggested that, within the limits of error of the methods used, there was no E secretion.Speculation: From previous studies in sheep, it was demonstrated that cortisol crossed the placenta from the mother to the fetus but that the fetus near term was also able to secrete cortisol. In this study of pregnant women we were able to calculate the maternal contribution to the fetal cortisol and cortisone concentration and to show that the fetus secretes three-fourths of its cortisol but that its cortisone was mainly maternal in origin. We were also able to show that cortisol and cortisone concentrations, similar to those at term, existed in utero as early as the 3rd month. We therefore speculate that the human fetal adrenal is capable of corticosteroid secretion early in pregnancy.

Plasma Aldosterone Concentration at Delivery and during the Newborn Period

Aldosterone concentrations in plasma of women on normal sodium intake undergoing cesarean section were 3.7+/-1.4 ng/100 ml (mean+/-1 SD). These values were significantly lower (P < 0.001) than those observed in mothers on normal sodium diet, delivered by the vaginal route (14.9+/-7.0 ng/100 ml). A significant elevation (P < 0.001) of the concentrations was found if the mothers had been on sodium restriction and/or diuretics (44.9+/-24.2 ng/100 ml). In supine position, adult nonpregnant subjects have aldosterone concentrations in plasma of 1.7+/-1.4 ng/100 ml on normal sodium intake and of 16.7+/-8.1 ng/100 ml on low sodium diet.Simultaneous determinations of aldosterone levels in cord blood showed that cord values were significantly higher than those of the corresponding mother (P < 0.01 by paired t test). However, values in cord blood of infants born to mothers on a normal sodium intake were significantly lower (P < 0.005) than those of infants whose mothers had required low sodium diet and/or diuretics during their pregnancy. Aldosterone concentrations in plasma of infants 1-72 hr of age and born to mothers on normal sodium intake were 25.9+/-11.7 ng/100 ml (mean +/-1 SD). These values were significantly lower (P < 0.005) than those of infants born to mothers on restricted sodium intake with or without diuretics (80.3+/-54.4 ng/100 ml). The concentrations at birth were not significantly different from those observed during the first 3 days of life (P > 0.6).

Transplacental passage and fetal secretion of aldosterone

The transplacental passage and the production of aldosterone were studied in late pregnancy during a constant infusion of 1,2-aldosterone-(3)H to mothers at the time of elective cesarean section. It was found that, while maternal aldosterone crossed the placenta, there was a significant secretion of aldosterone by the fetus. The aldosterone concentration in fetal plasma was 2-12 times higher than that of the corresponding mothers. Pregnancy had no effect on the metabolic clearance rate of aldosterone, but it increased the rate of production of this steroid. However, the increments that we observed were smaller than those reported in previous reports. The discrepancy was probably due to differences in body posture, our subjects being supine for at least 10 hr at the time of study.

Serum concentrations of epidermal growth factor in human pregnancy

Abstract A newly measurable peptide, epidermal growth factor (EGF), has been found in pregnant women with the use of a tube radioimmunoassay technique. This peptide appeared to have its highest concentrations during the early part of pregnancy, but measurable quantities were found in the serum throughout the entire course of the gestational period and within the cord blood. EGF was not found in the serum of male subjects, nonpregnant female subjects, and children. The origin and role of this compound remains to be determined, as well as its possible clinical usefulness.

Stromomyoma of the uterus

We present a solitary uterine tumor that occurred in a 28‐year‐old woman who complained of vaginal bleeding. Grossly, the tumor was well circumscribed and composed of lobulated tissue that varied from yellow, tan and soft, to white and rubbery. At the light microscopic level, areas identical to those described and interpreted as sex‐cord differentiation in a group of closely similar uterine tumors were found and obtained for electron microscopic study. Ultrastructurally, there were two basic types of cells, neither of which can be interpreted as sex‐cord derivatives. Cells that closely resembled the predominant components of Clement and Scullys group I tumors were similar to the normal endometrial stromal cells. Cells that formed plexiform cords demonstrated features diagnostic of smooth muscle cells. Cellular contents in cells comprising the tubular structures resembling that interpreted as indistinguishable from that of a Sertoli‐cell tumor (tubular androblastoma) were probably smooth muscle cells. We propose the term “Stromomyoma” to designate this peculiar uterine tumor. The similarity between our tumor and those reported in the literature raises the possibility that “uterine tumor resembling ovarian sex‐cord tumors” are actually stromomyomas.

Serum concentrations of β-melanocyte-stimulating hormone in human pregnancy

Abstract β-Melanocyte-stimulating hormone (β-MSH) has been measured in pregnant women with the use of a sensitive tube radioimmunoassay technique which does not require prior extraction. This peptide rises progressivley throughout pregnancy with its highest concentration at term. Measurable quantities exceeding maternal levels were observed in both cord blood and amniotic fluid and elevated levels of β-MSH were found in lactating women. The role and possible chorionic origin of β-MSH remain to be determined, as well as the possible clinical use.

A specific cytosolic estrogen receptor in human term placenta.

Administration of the antiestrogen ethamoxytriphetol (MER-25) during baboon gestation results in a marked decline in placental progesterone production. Since this effect in primates may be modulated via an estrogen receptor, the present study investigated the possible existence of an estrogen receptor in human placenta. Villous tissue of human, term placentas was homogenized in 0.01M Tris-HCl, ethylenediaminetetraacetic acid, dithiothreitol, glycerol buffer. Cytosol was incubated with 10(-8)M [3H] 17 beta-estradiol (E2) in the presence or absence of 10(-6)M diethylstilbestrol (DES). A single peak of [3H]E2 binding occurred in the 5.2 S region after glycerol density gradient centrifugation, which was competed for by DES, E2, and enclomiphene. Scatchard analysis demonstrated E2 binding, which was saturable, of high affinity (Kd = 1.90 X 10(11)M) and of low capacity (N = 0.13 X 10(-14) moles/mg cytosolic protein). Competition for [3H]E2 binding was DES greater than E2 greater than estrone greater than MER-25 greater than enclomiphene, whereas androgens, progestins, and corticosteroids were ineffective. The results fulfill the criteria for a specific estrogen receptor. The influence of antiestrogen and, possibly, estrogen upon placental function in baboons may be modulated by an estrogen receptor.

Studies on the level of blood progesterone throughout the course of labor

Abstract Serum progesterone was measured during the course of induced human labor utilizing a protein-binding technique. The results demonstrate a consistent fall at the onset of true labor with a return to prelabor levels during the accelerated phase of labor. A second fall was seen during the postpartum period. The possible significance of these results is discussed.

Observations on the level of blood oxytocinase throughout the course of labor and pregnancy

Abstract Serum oxytocinase (cysteine aminopeptidase activity) was measured during the course of induced human labor with the use of the hydrolysis of the synthetic substrate (cysteine aminopeptidase) technique. The results demonstrate a consistent fall at the onset of true labor with a return to prelabor levels during the accelerated phase of labor. A second fall was seen during the postpartum period. The possible significance of these results is discussed.

Metabolism of testosterone by virilizing Krukenberg tumor of the ovary

The metabolism of testosterone by a virilizing tumor was studied. A prominent coversion of testosterone to androstenedione was noted. The significance of this interrelationship was considered in terms of normal and abnormal ovarian steroidogenesis.