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

ABSTRACT. The goal of the study was the determination of the relative roles of the placenta and the fetus in causing low serum estriol (E3) levels in women bearing fetuses with intrauterine growth retardation (IUGR). Umbilical venous levels of E3 and dehydroepiandrosterone sulfate (DHAS) were measured in 31 samples from fetuses with IUGR, 21 of whom were vaginally delivered and 10 who were delivered by cesarean section. In addition, estrone (El) and estradiol (E2) were measured in 11 of the samples. The results were compared with 11 samples from cesarean section delivered control term infants and 54 samples from vaginally delivered control infants. The vaginally delivered IUGR group had a significantly lower mean umbilical venous DHAS level than did their control group (2128 + 158 ng/ml S E M versus 2645 + 130, p < 0.05). Both the vaginally delivered and cesarean section delivered IUGR infants had umbilical venous E3 levels significantly lower than in their control groups (70 2 1 0 ng/ml S E M versus 144 + 10, p < 0.001, and 46 2 1 1 ng/ml S E M versus 136 2 23, p < .01, respectively). Umbilical venous El and EZ levels were not different from the control values. El, EZ, E3, and DHAS were measured in eight maternal venous samples obtained from mothers bearing fetuses with IUGR. In comparison with 11 control mothes, only E3 was significantly different (10.7 + 3.0 ng/ml S E M in mothers with IUGR fetuses versus 25.0 + 4.9 in control mothersp < 0.01). The study provides evidence for reduced DHAS secretion in one group of the fetuses with IUGR, and no evidence for decreased placental conversion of DEIAS to the estrogens El and EZ. The significantly low E3 values in both umbilical and maternal samples are postulated to result not only from the reduced fetal adrenal DHAS secretion, but also underactive 16a-hydroxylase activity in fetal liver or low efficiency of 16a-OH-DHAS, relative to DHAS, as a substrate for placental conversion to an estrogen. (Pediatr Res 20: 166-168, 1986) Abbreviations IUGR, intrauterine growth retardation DHAS, dehydroepiandrosterone sulfate E,, estrone E2, estradiol E3, estriol Women bearing fetuses with IUGR frequently have low serum E3 levels in late gestation (1, 2). One origin of the low E3 production in these pregnancies may be reduced secretion of fetal adrenal cortex-derived neutral steroid precursors of estriol synthesis in the placenta (3). However, there is evidence that placental conversion of the neutral precursors to estrogen may be low in association with a fetus with IUGR (4). In order to investigate the relative importance of these two possible causes of low Ej production, umbilical venous, and maternal venous neutral steroid and estrogen levels were assessed in a series of pregnancies in which the fetus had IUGR. MATERIALS AND METHODSPatients. All pregnant women studied in this investigation were hospitalized in the Oregon Health Sciences University Hospital. Fetuses with IUGR were diagnosed when their birth weights were more than 2 SD below the mean for gestational age, as...

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“…Their activities show no correlation with urinary estrogen levels over a wide range of estrogen excretions (12).…”

Section: Discussionmentioning

confidence: 92%

“…In normal pregnancies, the placental enzymes are considered to have a large capacity, and not to be rate limiting in estrogen biosynthesis (12). Their activities show no correlation with urinary estrogen levels over a wide range of estrogen excretions (12).…”

Section: Discussionmentioning

confidence: 99%

Feto-Placental Steroid Metabolism in Growth Retarded Human Fetuses

1986

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“…The aromatization capacity of the diabetic placenta has been found to be reduced [26,27] or normal [28] in vitro. In vivo, low [29] or normal [30] aromatization of dehydroepiandrosterone (DHA) has been reported.…”

Section: Discussionmentioning

confidence: 99%

Plasma concentrations of unconjugated estrone, estradiol-17β and estriol, and HCS throughout pregnancy in diabetics and gestational diabetics

Hertogh¹,

Thomas²,

Hoet³

et al. 1976

Diabetologia

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Summary. Plasma unconjugated estrone (E~), estradiol-17/3 (E2) and estriol (E3) , and HCS were measured in the same plasma samples collected throughout pregnancy in 19 gestational diabetics (GD) and 21 diabetics (D). When compared to the results obtained in 22 normal subjects, plasma levels of E 1 and E 2 were significantly elevated in D in the second half of gestation. The results were intermediate although closer to the normals, in GD. E 3 values were not different from the normals in both D and GD. HCS values were lower than normal in early pregnancy in both D and GD. In late pregnancy HCS levels were not different from normal in either D or GD, although some individual values were much above the upper limit in some diabetic patients. The hormonal ratios in D and GD parallel those in normals, although E3/E 2 and HCS/E 2 were lower in D. These results are discussed with respect to the different behaviour of E 2 and E3, taking into accotmt the difference in their respective biosynthetic pathways. Besides a possible quantitative modification of the placental function in D, the results could tentatively be explained by a qualitative change in the fetal estrogen precursors to placental aromatization, in favour of the 16-non-hydroxylated compound. However, maternal modifications in precursor production or in estrogen metabolism can be an alternative hypothesis. Finally, the present work does not support the hypothetical estrogen deficiency in diabetic pregnancy. Estrogen treatment appears to have no objective justification.* This work was presented at the 1 lth annual meeting of the E. A.S.D., Munich September 1975 (Abstract 46, Diabetologia 11, 337, 1975.Key words: Estrone, estradiol, estriol, estrogens, diabetes, pregnancy, HCS, gestational diabetes, plasma levels.The hormonal environment in diabetic pregnancy has been the subject of many investigations, which have been extensively reviewed recently [1,2]. These works were aimed at showing the possible occurrence of endocrine dysfunction of the placenta, induced by the maternal diabetic environment, or of the fetus where adaptative mechanisms might have been stimulated by the particular metabolic situation. Yet, estrogen administration has been advocated as a necessary part of the treatment in diabetic pregnancy [3], in view of inferred hormonal insufficiency based on urine analysis [1,4].Controversy has arisen concerning the significance of urinary measurements [5], and conflicting results were reported [6]. Plasma measurements of estrogens also gave inconclusive results depending on the technique used, or the selection of patients [1,4,7], regarding for instance their state of equilibrium or the degree of illness. Low [8], high [9][10], and normal [11][12][13][14][15] values were reported for plasma estrogens. High [16,17] and normal [18,19] values were found for plasma HCS (human chorionic somatomammotropin).In the present study, unconjugated estrogens (estrone, estradiol-17/3 and estriol) and HCS were measured in the same plasma samples of a group of well tr...

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“…Med. 4 (1976) Brought to you by | The University of Auckland Library Authenticated Download Date | 6/4/15 11:15 PM either by competition with other steroid Substrates on which the enzyme acts, or non-competitively by direct negative feedback äs products of synthesis by the enzyme concerned [120,122]. TOWNSLEY has pointed out that enzyme capacity for certain steroid conversions in vitro may bear no relation to physiological conditions, in which enzyme activity depends on the balance of various steroids which together have cumulative inhibitory activity [120].…”

Section: 42 Enzyme Capacity and Control By Steroidsmentioning

confidence: 99%

“…The demonstration that estrogen production is affected by the concentration of steroid precursors and products at different enzymic Steps in the biosynthetic pathway [120,122], and that perfusion rate controls HCG and HPL production by the trophoblast (McNEiLLY et al, in preparation), suggest that blood flow, presumably both villous (i.e. fetal) and intervillous (i.e.…”

Section: Blood Flowmentioning

confidence: 99%

Review article

1976

Journal of Perinatal Medicine

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

Cited by 25 publications

References 11 publications

Feto-Placental Steroid Metabolism in Growth Retarded Human Fetuses

Feto-Placental Steroid Metabolism in Growth Retarded Human Fetuses

Plasma concentrations of unconjugated estrone, estradiol-17β and estriol, and HCS throughout pregnancy in diabetics and gestational diabetics

Review article

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