Origin of deoxycorticosterone and deoxycorticosterone sulfate in human pregnancy: Absence of steroid 21-sulfatase activity in sulfatase-deficient placenta

Guerami, Alireza; Varner, Michael W.; Shackleton, Cedric; MacDonald, Paul C.; Casey, M.Linette

doi:10.1016/0022-4731(88)90376-7

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…Our results suggested that the reduction in the level of hydroxyisocaproic acid during full-term pregnancy was associated with a decrease in the abundance of Lactobacillus. 21-hydroxypregnenolone could originate from the fetuses and its high concentration played an essential role in deoxycorticosterone synthesis during pregnancy ( Guerami et al, 1988 ). It was reported that 21-hydroxypregnenolone could be a biomarker of hypothalamic–pituitary–adrenal (HPA) axis abnormalities and immune dysfunction.…”

Section: Discussionmentioning

confidence: 99%

The interplay between the gut microbiota and metabolism during the third trimester of pregnancy

et al. 2022

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The gut microbiota undergoes dynamic changes during pregnancy. The gut microbial and metabolic networks observed in pregnant women have not been systematically analyzed. The primary purpose of this study was to explore the alterations in the gut microbiota and metabolism during late pregnancy and investigate the associations between the gut microbiota and metabolism. A total of thirty healthy pregnant women were followed from 30 to 32 weeks of gestation to full term. Fecal samples were collected for microbiome analysis and untargeted metabolomic analysis. The characteristics of the gut microbiota were evaluated by 16S ribosomal RNA gene sequencing of the V3-V4 regions. The plasma samples were used for untargeted metabolomic analysis with liquid chromatography–tandem mass spectrometry. The interplay between the gut microbiota and metabolism was analyzed further by bioinformatics approaches. We found that the relative abundances of Sellimonas and Megamonas were higher at full term, whereas that of Proteobacteria was lower. The correlation network of the gut microbiota tended to exhibit weaker connections from 32 weeks of gestation to the antepartum timepoint. Changes in the gut microbiota during late pregnancy were correlated with the absorbance and metabolism of microbiota-associated metabolites, such as fatty acids and free amino acids, thereby generating a unique metabolic system for the growth of the fetus. Decreasing the concentration of specific metabolites in plasma and increasing the levels of palmitic acid and 20-hydroxyarachidonic acid may enhance the transformation of a proinflammatory immune state as pregnancy progresses.

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Section: Discussionmentioning

confidence: 99%

The interplay between the gut microbiota and metabolism during the third trimester of pregnancy

et al. 2022

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“…A question remains as to whether disulfation is purely a catabolic reaction or if such steroids could be transportable reservoirs of active hormone precursors, as is likely the case for DHEA and estrone sulfates. Guerami et al (1988) have proposed that 21OHPreg-diS is an 11-deoxycorticosterone (DOC) precursor during pregnancy, particularly since circulating levels of this mineralocorticoid and its sulfate are increased during gestation (Corsan et al 1997). It is known that the placenta is capable of hydrolyzing 21-sulfates and the enzyme responsible is the usual STS as 21-desulfation does not occur in STSD (Guerami et al 1988).…”

Section: Discussionmentioning

confidence: 99%

“…Guerami et al (1988) have proposed that 21OHPreg-diS is an 11-deoxycorticosterone (DOC) precursor during pregnancy, particularly since circulating levels of this mineralocorticoid and its sulfate are increased during gestation (Corsan et al 1997). It is known that the placenta is capable of hydrolyzing 21-sulfates and the enzyme responsible is the usual STS as 21-desulfation does not occur in STSD (Guerami et al 1988). Another possible reservoir for disulfates is 5AD(17β)-diS, potentially a testosterone or estradiol precursor.…”

Section: Discussionmentioning

confidence: 99%

“…Besides the increased excretion of 3β5αPD-diS, we also observed an increase in the transitions corresponding to 5PD-diS and 3β,21-dihydroxy-5α-pregnan-20-one disulfate (21OHPreg3β5α-diS), the latter in spite of a likely POR requirement by fetal 21-hydroxylase. However, it should be noted that this fetal enzyme differs from that coded by CYP21A2 required in cortisol synthesis (Guerami et al 1988, Corsan et al 1997.…”

Section: Figurementioning

confidence: 92%

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SULFATION PATHWAYS: Alternate steroid sulfation pathways targeted by LC–MS/MS analysis of disulfates: application to prenatal diagnosis of steroid synthesis disorders

Pozo

Marcos

Khymenets

et al. 2018

Journal of Molecular Endocrinology

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The steroid disulfates ( bis-sulfates) are a significant but minor fraction of the urinary steroid metabolome that have not been widely studied because major components are not hydrolyzed by the commercial sulfatases commonly used in steroid metabolomics. In early studies, conjugate fractionation followed by hydrolysis using acidified solvent (solvolysis) was used for the indirect detection of this fraction by GC-MS. This paper describes the application of a specific LC-MS/MS method for the direct identification of disulfates in urine, and their use as markers for the prenatal diagnosis of disorders causing reduced estriol production: STSD (steroid sulfatase deficiency), SLOS (Smith-Lemli-Opitz syndrome) and PORD (P450 oxidoreductase deficiency). Disulfates were detected by monitoring a constant ion loss (CIL) from the molecular di-anion. While focused on disulfates, our methodology included an analysis of intact steroid glucuronides and monosulfates because steroidogenic disorder diagnosis usually requires an examination of the complete steroid profile. In the disorders studied, a few individual steroids (as disulfates) were found particularly informative: pregn-5-ene-3β,20-diol, pregn-5-ene-3β,21-diol (STSD, neonatal PORD) and 5α-pregnane-3β,20-diol (pregnancy PORD). Authentic steroid disulfates were synthesized for use in this study as aid to characterization. Tentative identification of 5ξ-pregn-7-ene-3ξ,20-diol and 5ξ-pregn-7-ene-3ξ,17,20-triol disulfates was also obtained in samples from SLOS affected pregnancies. Seven ratios between the detected metabolites were applied to distinguish the three selected disorders from control samples. Our results show the potential of the direct detection of steroid conjugates in the diagnosis of pathologies related with steroid biosynthesis.

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The development of tamoxifen for breast cancer therapy: A tribute to the late Arthur L. Walpole

Jordan¹

1988

Breast Cancer Res Tr

119

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Tamoxifen, a nonsteroidal antiestrogen, is now the endocrine treatment most widely used in breast cancer, both in the adjuvant and advanced disease settings. Here we will trace the development of tamoxifen for advanced breast cancer in postmenopausal patients, consider the biological basis for the recent successful use of tamoxifen for long-term adjuvant therapy, and discuss the use of tamoxifen in premenopausal patients with advanced disease. In part, this will be a historical review offered as a tribute to the late Dr. Arthur L. Walpole, who must receive the chief credit for the discovery of tamoxifen and its subsequent application as an anticancer agent.

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Origin of deoxycorticosterone and deoxycorticosterone sulfate in human pregnancy: Absence of steroid 21-sulfatase activity in sulfatase-deficient placenta

Cited by 6 publications

References 21 publications

The interplay between the gut microbiota and metabolism during the third trimester of pregnancy

The interplay between the gut microbiota and metabolism during the third trimester of pregnancy

SULFATION PATHWAYS: Alternate steroid sulfation pathways targeted by LC–MS/MS analysis of disulfates: application to prenatal diagnosis of steroid synthesis disorders

The development of tamoxifen for breast cancer therapy: A tribute to the late Arthur L. Walpole

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