Four cases of pregnancy with low estrogen production due to placental enzymatic deficiency

Mango, D.; Montemurro, A.; Scirpa, P.; Bompiani, A; Menini, E.

doi:10.1016/0028-2243(78)90129-6

Cited by 18 publications

(6 citation statements)

References 18 publications

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“…Although a suspected patient was described some years ago (30), there is only one other definitively documented case of placental aromatase deficiency, in a Japanese infant. In 1991, Shozu et al (18) described a 24-year-old primigravida who showed progressive virilization during the third trimester.…”

Section: Resultsmentioning

confidence: 99%

Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries.

Ito

Fisher

Conte

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

197

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We identified two mutations in the CYP19 gene responsible for aromatase deficiency in an 18-year-old 46,XX female with ambiguous external genitalia at birth, primary amenorrhea and sexual infantilism, and polycystic ovaries. The coding exons, namely exons II-X, of the CYP19 gene were amplified by PCR from genomic DNA and sequenced directy. Direct sequencing of the ampled DNA from the patient revealed two single-base changes, at bp 1303 (C-+ T) and bp 1310 (G -p A) in exon X, which were newly found missense mutations and reulted in codon changes of R435C and C437Y, respectively. Subconlng followed by sequencing confirmed that the patient is a compound heterozygote. The results ofrestriction frgment length polymorphism analysis and direct sequencing of the ampliied exon X DNA from the patient's mother indicate maternal inheritance of the R435C mutation. Transient expression experiments showed that the R435C mutant protein had =1.1% of the activity of the wild type, whereas C437Y was totally inactive. Cysteine-437 is the conserved cysteine in the heme-binding region believed to serve as the fifth coordinating ligand of the heme iron. To our knowledge, this patient is the first adult to have described the cardinal features of a syndrome of aromatase deficiency. Recognition that such defects exist will lead to a better understanding of the role of this enzyme in human development and disea.The biosynthesis ofestrogens from Clg steroids is catalyzed by an enzyme complex known as aromatase, whose activity results in aromatization ofthe A ring of androgens to form the phenolic A ring characteristic of estrogens, with concomitant loss of the Clg angular methyl group (1, 2). This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells and consists oftwo components. The first is a form of cytochrome P450 named aromatase cytochrome P450 (P450arom), the product of the CYP19 gene (3). The second component, NADPH-cytochrome P450 reductase, a ubiquitous flavoprotein of the endoplasmic reticulum of most cell types, transfers reducing equivalents to the P450arom, which binds the C19 substrate and catalyzes the insertion of oxygen into the molecule, resulting in the formation of C18 estrogens

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Section: Resultsmentioning

confidence: 99%

Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries.

Ito

Fisher

Conte

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

197

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“…Actually, it has been two decades since placental aromatase deficiency was first reported by Mango et al by incubation studies in vitro of the delivered placenta in a primigravida with low urinary oestrogens during the third trimester of pregnancy (97). However, neither the mother nor the female infant exhibited evidence of virilization.…”

Section: Journal Of Endocrinology (1999) 140mentioning

confidence: 99%

Oestrogen deficiency in men: where are we today?

Faustini‐Fustini

Rochira

Carani

1999

European Journal of Endocrinology

121

105

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“…For example, Tabei and Heinrichs [150] observed that in vitro incubation of a homogenate of a sulfatase-deficient placenta could convert déhydro épiandrostérone to estrone and estradiol [ 150] in the same or greater yield (40-50%) as did a normal placenta (43%). Reduced aromatase activity in a sulfatase-deficient pla centa was also reported by Mango et al [151]. Bedin et al [152] compared aromatase activity in 9 sulfatase-defi cient placentas with nine normal placentas.…”

Section: Placental Biosynthesis Of Estradiolmentioning

confidence: 77%

Are Estradiol-Producing Cells Incompletely Endowed? A Chronicle of the Emergence of Certitude from Conjecture

Lieberman¹

1996

Gynecol Obstet Invest

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Four cases of pregnancy with low estrogen production due to placental enzymatic deficiency

Cited by 18 publications

References 18 publications

Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries.

Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries.

Oestrogen deficiency in men: where are we today?

Are Estradiol-Producing Cells Incompletely Endowed? A Chronicle of the Emergence of Certitude from Conjecture

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