The ADRENOGENITAL SYNDROME WITH DEFICIENCY OF 3β-Hydroxysteroid DEHYDROGENASE*

Bongiovanni, Alfred M.

doi:10.1172/jci104666

Cited by 293 publications

(80 citation statements)

References 20 publications

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“…An inverse association between shorter male AGD in human infants and prenatal phthalate exposure (particularly di-(2-ethylhexyl) phthalate (DEHP) and di-n-butyl Developmental bisphenol A exposure in rats phthalate (DBP)) has also been reported (Swan et al 2005, Swan 2008. Similarly, girls androgenised due to congenital adrenal hyperplasia have longer AGD compared with healthy girls (Bongiovanni & Kellenbenz 1962). This suggests that AGD can also be a predictor of persistent disturbances in human sexual differentiation.…”

Section: Discussionmentioning

confidence: 98%

Low-dose effects of bisphenol A on early sexual development in male and female rats

Christiansen¹,

Axelstad²,

Boberg³

et al. 2014

Reproduction

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Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been reported to impair many endpoints for reproductive and neurological development; however, it is controversial whether BPA has effects in the microgram per kilogram dose range. The aim of the current study was to examine the influence of BPA on early sexual development in male and female rats at dose levels covering both regulatory no observed adverse effect levels (NOAELs) (5 and 50 mg/kg bw per day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25 mg/kg bw per day). Time-mated Wistar rats (nZ22) were gavaged during pregnancy and lactation from gestation day 7 to pup day 22 with 0, 0.025, 0.25, 5 or 50 mg/kg bw per day BPA. From 0.250 mg/kg and above, male anogenital distance (AGD) was significantly decreased, whereas decreased female AGD was seen from 0.025 mg/kg bw per day and above. Moreover, the incidence of nipple retention in males appeared to increase dose relatedly and the increase was statistically significant at 50 mg/kg per day. No significant changes in reproductive organ weights in the 16-day-old males and females and no signs of maternal toxicity were seen. The decreased AGD at birth in both sexes indicates effects on prenatal sexual development and provides new evidence of low-dose adverse effects of BPA in rats in the microgram per kilogram dose range. The NOAEL in this study is clearly below 5 mg/kg for BPA, which is used as the basis for establishment of the current tolerable daily intake (TDI) by EFSA; thus a reconsideration of the current TDI of BPA appears warranted.

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Section: Discussionmentioning

confidence: 98%

Low-dose effects of bisphenol A on early sexual development in male and female rats

Christiansen¹,

Axelstad²,

Boberg³

et al. 2014

Reproduction

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“…Gene SalF7L is predicted to encode a 39.3K protein with a similar size and 34% amino acid identity to human and bovine 3 fl-HSD Zhao et al, 1989). This is a key enzyme in steroid biosynthesis and disease (adrenogenital syndrome) ensues from its deficiency in humans (Bongiovanni, 1962). Gene SalF8R encodes a 13.6K protein with 39~ amino acid identity with Cu-Zn superoxide dismutase (SOD), an enzyme that catalyses the dismutation of superoxide OF to oxygen and hydrogen peroxide (McCord & Fridovich, 1969).…”

Section: (I) Genes Potentially Encoding Enzymesmentioning

confidence: 99%

Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near the right inverted terminal repeat

Smith

Chan

Howard

1991

Journal of General Virology

155

107

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The nucleotide sequence of 42 090 bp of vaccinia virus strain WR is presented. The sequence includes the SalI L, F, G and I fragments and starts near the centre of the HindIII A fragment and extends rightwards towards the genomic terminus, finishing approximately 0-5 kb internal of the inverted terminal repeat (ITR). Translation of this region has identified 65 open reading frames (ORFs) of greater than 65 amino acids in length. Fifty-one of these which do not extensively overlap other larger ORFs have been subjected to further analysis; the other 14 are termed minor ORFs. In the rightmost 28.7 kb, the genes are, with one exception, transcribed towards the genomic terminus, similar to the arrangement of genes at the left end of the virus genome. Internal of this region the genes are expressed off either DNA strand but still predominately rightwards. ORFs are tightly packed with few intergenic non-coding regions of greater than 250 bp. Protein sequence comparisons have established a remarkably high number of homologies with entries in existing protein databases. Of these, DNA ligase, thymidylate kinase, two serine-threonine protein kinases, two serine proteinase inhibitors (serpins), two interleukin-1 receptor homologues and a discontinuous ORF related to tumour necrosis factor receptor have been reported. Other homologies include lectins, profilin, 3fl-hydroxy steroid dehydrogenase, superoxide dismutase, guanylate kinase, ankyrin and complement factor H. In addition, there are a number of polypeptides with predicted properties of membraneassociated, secretory or glyco-proteins. Twelve gene families are described here and elsewhere. There is considerable similarity between genes from the right and left end of the virus genome that may have arisen by terminal transposition events. Several differences from the corresponding region of vaccinia virus strain Copenhagen sequence are noted. Near the right terminus the sequences diverge completely, and internal of this there are multiple examples of deletion of short sequences (eight to 10 nucleotides) that lie within penta-or hexanucleotide direct repeats.

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“…A hiperplasia adrenal congênita decorrente da deficiência da enzima 3β-hidroxiesteróide desidrogenase (3βHSD) é uma doença autossômica recessiva rara, descrita em 1962 por Bongiovanni (32). O gene 3βHSD encontra-se no cromossomo 1p13.1 e possui 4 exons, 3 introns e uma região 5' flanqueadora (33).…”

Section: Hiperplasia Adrenal Congênita Por Deficiência Da Enzima 3β βunclassified

Causas raras de pseudo-hermafroditismo feminino: quando suspeitar?

Castro

Elias

2005

Arq Bras Endocrinol Metab

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RESUMONeste artigo discutiremos as causas raras de pseudo-hermafroditismo feminino. Hiperplasia congênita adrenal é a causa mais comum da ambigüidade da genitalia externa no nascimento, em fetos 46,XX, devido principalmente à forma clássica de deficiência de 21-hidroxilase. São apresentadas aqui as deficiências de 11β-hidroxilase e de 3β-hidroxiesteroide desidrogenase, além da resistência familial aos glicocorticóides, caracterizada pela secreção aumentada de cortisol sem evidência clínica de hipercortisolismo, mas com manifestations de excesso de andrógenos e de mineralocorticóides, decorrente de mutações no gene do receptor do glucocorticóide. Também são discutidas a deficiência de aromatase placentária, caracterizada por masculinização do feto feminino, acompanhada de virilização materna durante a gestação, e deve ser considerada na ausência da hiperplasia adrenal fetal e de tumores maternos produtores de andrógenos e a deficiência da P450-oxidorredutase, além das causas maternas e de quadros dismórficos complexos que levam ao pseudo-hermafroditismo feminino. A investigação requer a análise do cariótipo, dosagens séricas iniciais de 17OH progesterona, 11 desoxicortisol, 17-pregnenolone e andrógenos para avaliar o diagnóstico das diferentes causas de hiperplasia adrenal congênita. Após este diagnóstico ser afastado, dados clínicos e laboratoriais devem ser coletados para afastar as causas ainda mais raras de pseudo-hermafroditismo feminino. The congenital adrenal hyperplasia is the commonest cause of ambiguity of the external genitalia at birth, due to classic forms of 21-hydroxylase and 11β-hydroxylase deficiencies. 3β-hydroxysteroid dehydrogenase (3βHSD) is a rare disorder that affects both sexes and female patients may have ambiguous genitalia. Familial glucocorticoid resistance is characterized by increased cortisol secretion without clinical evidence of hypercortisolism, but with manifestations of androgen and mineralocorticoid excess, caused by glucocorticoid receptor gene mutation, and rarely can lead to female pseudohermaphroditism. Placental aromatase deficiency is a rare disease characterized by a masculinized female fetus and a virilized mother, which should be considered in the absence of fetal adrenal hyperplasia and maternal androgen-secreting tumours. Finally, mutations of P450 oxidoreductase causes disordered steroidogenesis with ambiguous genitalia. The investigation of abnormal sexual development requires an initial karyotype analysis and serum 17OH progesterone, 11 deoxycortisol, 17 pregnenolone, and androgen measurements to assess the diagnosis of different forms of congenital adrenal hyperplasia.

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The ADRENOGENITAL SYNDROME WITH DEFICIENCY OF 3β-Hydroxysteroid DEHYDROGENASE*

Cited by 293 publications

References 20 publications

Low-dose effects of bisphenol A on early sexual development in male and female rats

Low-dose effects of bisphenol A on early sexual development in male and female rats

Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near the right inverted terminal repeat

Causas raras de pseudo-hermafroditismo feminino: quando suspeitar?

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