Low estriol levels in the maternal marker screen as a predictor of X-linked adrenal hypoplasia congenita: Case report

Durkovic, Jasmina; Milenković, Tatjana; Krone, Nils; Parajes, Silvia; Mandić, Bojana

doi:10.2298/sarh1412728d

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…Prenatal estriol, derived from fetal adrenal 16α‐dehydroepiandrosterone after a series of steps (the last step being aromatization), is a marker of fetal well‐being, and a low estriol level, while not specific, may be an early indication of adrenal insufficiency. The association of low prenatal estriol and adrenal hypoplasia congenita has been reported previously …”

Section: Introductionmentioning

confidence: 74%

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A novel de novo frameshift mutation in NR0B1 and low prenatal estriol in adrenal hypoplasia congenita

Khattab

Nelson‐Williams

Cabreza

et al. 2018

Annals of the New York Academy of Sciences

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Mutations in the gene NR0B1 have been associated with several clinical phenotypes of X-linked adrenal hypoplasia congenita (AHC). The degree and onset of adrenal insufficiency and involvement of hypogonadotropic hypogonadism is variable and may not be concordant with the identified mutation. We review a patient with AHC in which prenatal estriol levels were low, presenting with early-onset mineralocorticoid deficiency in the newborn period followed by glucocorticoid deficiency 2 years later. The reported child is hemizygous for a novel mutation that is deemed de novo in the ligand-binding site of the protein (DAX1) expressed by NR0B1. The identified frameshift mutation results in a T407N/fs protein change. Low prenatal estriol levels may represent a sensitive marker of potentially fatal disorders associated with adrenal insufficiency and should be utilized more frequently. Additionally, accurate reporting of mutations in NR0B1 and the associated phenotype are important to eventually establish a genotype-phenotype correlation that may help anticipate guidance in AHC.

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Section: Introductionmentioning

confidence: 74%

“…Prenatal estriol levels are linked to fetal well‐being and therefore low levels should alert physicians to the possibility of adrenal failure requiring treatment in the newborn period …”

Section: Discussionmentioning

confidence: 99%

A novel de novo frameshift mutation in NR0B1 and low prenatal estriol in adrenal hypoplasia congenita

Khattab

Nelson‐Williams

Cabreza

et al. 2018

Annals of the New York Academy of Sciences

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“…Among estrogen, E3 had the strongest effect on TMEM16A (Figure 4). E3 is mainly synthesized in the placenta from 16α-hydroxydehydroepiandrosterone, which is generated in the fetal liver (Thomas and Potter, 2013;Durkovic et al, 2014). These facts indicate that TMEM16A activity is down-regulated during pregnancy.…”

Section: Discussionmentioning

confidence: 97%

The Calcium-Activated Chloride Channel TMEM16A is Inhibitied by Liquiritigenin

2021

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The transmembrane 16 (TMEM16) family contains 10 subtypes, and the function of each protein is different. TMEM16A is a calcium-activated chloride channel involved in physiological and pathological situations. Liquiritigenin is an aglycone derived from Glycyrrhiza glabra, and it is generated via the metabolism of enterobacterial flora. It has been known that liquiritigenin reduces pain sensation involving TMEM16A activation in primary sensory neurons. In addition, other pharmacological effects of liquiritigenin in physiological functions involving TMEM16A have been reported. However, the relationship between TMEM16A and liquiritigenin is still unknown. Therefore, we hypothesized that TMEM16A is inhibited by liquiritigenin. To confirm this hypothesis, we investigated the effect of liquiritigenin on TMEM16A currents evoked by intracellular free calcium in HEK293T cells transfected with TMEM16A. In this study, we found that liquiritigenin inhibited the mouse and human TMEM16A currents. To further confirm its selectivity, we also investigated its pharmacological effects on other ion channels, including transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), which are non-selective cation channels involved in pain sensation. However, liquiritigenin did not inhibit the currents of TRPV1 and TRPA1 induced by capsaicin and allyl isothiocyanate, respectively. Therefore, our findings indicate that selective TMEM16A inhibition could be one molecular mechanism that explains liquiritigenin-induced pain reduction. Additionally, we also investigated the inhibitory effects of estrogens on TMEM16A because liquiritigenin reportedly binds to the estrogen receptor. In this study, a pregnancy-dependent estrogen, estriol, significantly inhibited TMEM16A. However, the efficacy was weak. Although there is a possibility that TMEM16A activity could be suppressed during pregnancy, the physiological significance seems to be small. Thus, the inhibitory effect of estrogen might not be significant under physiological conditions. Furthermore, we investigated the effect of dihydrodaidzein, which is an analog of liquiritigenin that has a hydroxyphenyl at different carbon atom of pyranose. Dihydrodaidzein also inhibited mouse and human TMEM16A. However, the inhibitory effects were weaker than those of liquiritigenin. This suggests that the efficacy of TMEM16A antagonists depends on the hydroxyl group positions. Our finding of liquiritigenin-dependent TMEM16A inhibition could connect the current fragmented knowledge of the physiological and pathological mechanisms involving TMEM16A and liquiritigenin.

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“…A previous study showed that pregnant women with an anencephalic fetus (in which levels of ACTH secreted from the fetal pituitary gland are markedly reduced), the levels of circulating E3 are very low as a result of impaired development of the fetal zone ( 40 ). Fetal adrenal hypoplasia is a rare condition that presents as marked low maternal serum levels of E3 during the second trimester ( 41 ). In our study, the last antenatal care recorded is normal for all subjects.…”

Section: Discussionmentioning

confidence: 99%

Effect of maternal body mass index on the steroid profile in women with gestational diabetes mellitus

Sun

Zhu²,

Meng³

et al. 2022

Front. Endocrinol.

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ObjectiveTo explore the effect of maternal body mass index (BMI) on steroid hormone profiles in women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT).MethodsWe enrolled 79 women with NGT and 80 women with GDM who had a gestational age of 24–28 weeks. The participants were grouped according to their BMI. We quantified 11 steroid hormones profiles by liquid chromatography-tandem mass spectrometry and calculated the product-to-precursor ratios in the steroidogenic pathway.ResultsWomen with GDM and BMI<25kg/m2 showed higher concentrations of dehydroepiandrosterone (DHEA) (p<0.001), testosterone (T) (p=0.020), estrone (E1) (p=0.010) and estradiol (E2) (p=0.040) and lower Matsuda index and HOMA-β than women with NGT and BMI<25kg/m2. In women with GDM, concentrations of E1 (p=0.006) and E2 (p=0.009) declined, accompanied by reduced E2/T (p=0.008) and E1/androstenedione (A4) (p=0.010) in the BMI>25 kg/m2 group, when compared to that in the BMI<25 kg/m2 group. The values of E2/T and E1/A4 were used to evaluate the cytochrome P450 aromatase enzyme activity in the steroidogenic pathway. Both aromatase activities negatively correlated with the maternal BMI and positively correlated with the Matsuda index in women with GDM.ConclusionsNGT women and GDM women with normal weight presented with different steroid hormone profiles. Steroidogenic pathway profiling of sex hormones synthesis showed a significant increase in the production of DHEA, T, E1, and E2 in GDM women with normal weight. Additionally, the alteration of steroid hormone metabolism was related to maternal BMI in women with GDM, and GDM women with overweight showed reduced estrogen production and decreased insulin sensitivity compared with GDM women with normal weight.

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Low estriol levels in the maternal marker screen as a predictor of X-linked adrenal hypoplasia congenita: Case report

Abstract: Since determination of E3 is a simple, sensitive, noninvasive and cheap method, its use as an obligatory prenatal screening test should be accepted as a standard practice in Serbia.

Cited by 7 publications

References 12 publications

A novel de novo frameshift mutation in NR0B1 and low prenatal estriol in adrenal hypoplasia congenita

A novel de novo frameshift mutation in NR0B1 and low prenatal estriol in adrenal hypoplasia congenita

The Calcium-Activated Chloride Channel TMEM16A is Inhibitied by Liquiritigenin

Effect of maternal body mass index on the steroid profile in women with gestational diabetes mellitus

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