Genetic Disorders of Male Sexual Differentiation

Fichman, Kaye R.; Migeon, Barbara R.; Migeon, Claude J.

doi:10.1007/978-1-4615-8288-5_5

Cited by 5 publications

(3 citation statements)

References 147 publications

(49 reference statements)

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“…The complete form of the androgen insensitivity syndrome, which is frequently but rather inappropriately designated'testicular feminization', is transmitted via a recessive gene localized on the X-chromosome (41). This condition has been described in mice (Lyon-Hawkes mutation) (60,61), rats (Stanley-Gumbreck mutation) (62,63) and man (64,65), as well as other mammalian species.…”

Section: Pathophysiology: Complete Androgen Insensitivit)'mentioning

confidence: 97%

“…Our laboratory has made its most significant contributions toward defining the mechanism of androgen action mediated by the intracellular androgen receptor (1, 41,42). In particular, studies in our laboratory and in others with cultured human skin fibroblasts have contributed greatly to the understanding of the biochemical and genetic mechanisms associated with the androgen insensitivity syndrome.…”

Section: Androgen Receptor In Skin Fibroblastsmentioning

confidence: 99%

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Cultured human skin fibroblasts: a model for the study of androgen action

Brown

Migeon

1981

Mol Cell Biochem

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Human skin may be considered as a target organ for androgens, as are male sex accessory organs, since all events involved in testosterone action have been observed in this tissue. As a corollary, the mechanism of androgen action can be studied in vitro in cultured skin fibroblasts. The advantages of this system are that studies can be performed with intact human cells under carefully controlled conditions, differentiated genetic and biochemical characteristics of the cells are faithfully preserved and the biological material is renewable from a single biopsy specimen. The metabolism of androgens, in particular the 5 alpha-reduction of testosterone to the active metabolite, dihydrotestosterone, the intracellular binding of androgen to its specific receptor protein and its subsequent translocation to the nucleus have been studied in skin fibroblasts. The intracellular androgen receptor content of genital skin fibroblasts is higher than that from nongenital skin sites. In addition, the androgen receptor has been characterized as a specific macromolecule with properties of high affinity and low capacity similar to that of other steroid hormone receptors. The pathophysiology of three genetic mutations which alter normal male sexual development and differentiation has been identified in the human skin fibroblast system. In 5 alpha-reductase deficiency, an autosomal recessive disorder in which dihydrotestosterone formation is impaired, virilization of the Wolffian ducts is normal but the external genitalia and urogenital sinus derivatives are female in character. At least two types of X-linked disorders of the androgen receptor exist such that the actions of both testosterone and dihydrotestosterone are impaired and developmental abnormalities may involve both Wolffian derivatives and the external genitalia as well. These two forms of androgen insensitivity result from either the absence of androgen receptor binding activity (receptor (-) form) or apparently normal androgen receptor binding with absence of an appropriate biological response (receptor (+) form). In addition, studies with human skin fibroblasts may also be of value in defining the cellular mechanisms underlying the broad spectrum of partial defects in virilization. In summary, we have correlated our studies of the molecular mechanism of androgen action in human genital skin fibroblasts with those of other investigators as these studies contribute to our understanding of male sexual development and differentiation.

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Section: Pathophysiology: Complete Androgen Insensitivit)'mentioning

confidence: 97%

Section: Androgen Receptor In Skin Fibroblastsmentioning

confidence: 99%

Cultured human skin fibroblasts: a model for the study of androgen action

Brown

Migeon

1981

Mol Cell Biochem

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“…Male pseudohermaphroditism in humans is defined as a condition of incomplete masculinization of the fetal external genitalia in a karyotypically normal 46,XY individual (1). Among the multiple genetic disorders that result in male pseudohermaphroditism are a group of abnormalities of the androgen target cells, including Sa-reductase deficiency and androgen insensitivity (2,3).…”

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confidence: 99%