Variation in steroid 5 alpha-reductase activity in cloned human skin fibroblasts. Shift in phenotypic expression from high to low activity upon subcloning.

Griffin, James E.; Allman, D R; Durrant, J L; Wilson, Jean D.

doi:10.1016/s0021-9258(19)69504-9

Cited by 36 publications

(1 citation statement)

References 22 publications

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“…5␣-Reductase 2 activity can be influenced by either clonal origin of the cell line (23) or by the site of origin of the biopsies (24). Therefore, two different GSF cell lines from subject II-5 (GSF 1 and 2) derived from separate biopsies taken 1.5 yr apart were used for the studies.…”

Section: ␣-Reductase 2 Assaymentioning

confidence: 99%

Phenotypic Variation in a Family with Partial Androgen Insensitivity Syndrome Explained by Differences in 5 Dihydrotestosterone Availability

Boehmer¹

2001

Journal of Clinical Endocrinology & Metabolism

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Mutations in the androgen receptor (AR) gene result in a wide range of phenotypes of the androgen insensitivity syndrome (AIS). Inter- and intrafamilial differences in the phenotypic expression of identical AR mutations are known, suggesting modifying factors in establishing the phenotype. Two 46,XY siblings with partial AIS sharing the same AR gene mutation, R846H, but showing very different phenotypes are studied. Their parents are first cousins. One sibling with grade 5 AIS was raised as a girl; the other sibling with grade 3 AIS was raised as a boy. In both siblings serum levels of hormones were measured; a sex hormone-binding globulin (SHBG) suppression test was completed; and mutation analysis of the AR gene, Scatchard, and SDS-PAGE analysis of the AR protein was performed. Furthermore, 5alpha-reductase 2 expression and activity in genital skin fibroblasts were investigated, and the 5alpha-reductase 2 gene was sequenced. The decrease in SHBG serum levels in a SHBG suppression test did not suggest differences in androgen sensitivity as the cause of the phenotypic variation. Also, androgen binding characteristics of the AR, AR expression levels, and the phosphorylation pattern of the AR on hormone binding were identical in both siblings. However, 5alpha-reductase 2 activity was normal in genital skin fibroblasts from the phenotypic male patient but undetectable in genital skin fibroblasts from the phenotypic female patient. The lack of 5alpha-reductase 2 activity was due to absent or reduced expression of 5alpha-reductase 2 in genital skin fibroblasts from the phenotypic female patient. Exon and flanking intron sequences of the 5alpha-reductase 2 gene showed no mutations in either sibling. Additional intragenic polymorphic marker analysis gave no evidence for different inherited alleles for the 5alpha-reductase 2 gene in the two siblings. Therefore, the absent or reduced expression of 5alpha-reductase 2 is likely to be additional to the AIS. Distinct phenotypic variation in this family was caused by 5alpha-reductase 2 deficiency, additional to AIS. This 5alpha-reductase deficiency is due to absence of expression of the 5alpha-reductase iso-enzyme 2 as shown by molecular studies. The distinct phenotypic variation in AIS here is explained by differences in the availability of 5alpha-dihydrotestosterone during embryonic sex differentiation.

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Section: ␣-Reductase 2 Assaymentioning

confidence: 99%

Phenotypic Variation in a Family with Partial Androgen Insensitivity Syndrome Explained by Differences in 5 Dihydrotestosterone Availability

Boehmer¹

2001

Journal of Clinical Endocrinology & Metabolism

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Intraclonal diversity of fibrosarcoma cells for the production of macrophage colony‐stimulating factor and granulocyte colony‐stimulating factor

Sakai

Kubota²,

Shikita³

et al. 1987

Journal Cellular Physiology

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A new cell line was established from fibrosarcoma that had spontaneously developed in a mouse. The cells were maintained growing in culture for two years and constantly produced both macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF). Cloning of the cells by anchorage-independent colony formation gave subclones showing the activity of producing M-CSF and G-CSF in different proportions, whereas no subclone produced G-CSF without producing M-CSF simultaneously. Recloning of the bipotential subclones again gave clonal derivatives producing two types of CSF in various proportions. The observed heterogeneity of the cloned cells seems to be an epigenetic phenomenon, because the cells resumed the G-CSF producing activity in the absence of cell proliferation. After equilibrium was achieved, all of the subclones produced both M-CSF and G-CSF nearly in equal proportions. Tumorigenic and leukocytosis-inducing activity of the cloned cells was nearly comparable with the activity of the original tumor cells.

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Androgen Insensitivity Syndromes:Paradox of Phenotypic Feminization with Male Genotype and Normal Testicular Androgen Secretion

Brown¹,

Migeon²

1987

Hormone Resistance and Other Endocrine Paradoxes

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Variation in steroid 5 alpha-reductase activity in cloned human skin fibroblasts. Shift in phenotypic expression from high to low activity upon subcloning.

Cited by 36 publications

References 22 publications

Phenotypic Variation in a Family with Partial Androgen Insensitivity Syndrome Explained by Differences in 5 Dihydrotestosterone Availability

Phenotypic Variation in a Family with Partial Androgen Insensitivity Syndrome Explained by Differences in 5 Dihydrotestosterone Availability

Intraclonal diversity of fibrosarcoma cells for the production of macrophage colony‐stimulating factor and granulocyte colony‐stimulating factor

Androgen Insensitivity Syndromes:Paradox of Phenotypic Feminization with Male Genotype and Normal Testicular Androgen Secretion

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