Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene

Sinnecker, G. H. G.; Hiort, Olaf; Nitsche, Esther M.; Holterhus, Paul‐Martin; Kruse, K.; Group, German Collaborative Intersex Study

doi:10.1007/s004310050542

Cited by 119 publications

(72 citation statements)

References 30 publications

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“…This suggests that the critical window for androgen action in penis formation is not restricted just to the EW (E15.5-E17.5), but that androgen action for at least some of the MW (E17.5-E19.5) is also essential. This gradient of phallus development has also been reported in humans with androgen insensitivity syndrome, in which structures range from a normal male phallus to a hypospadiac male phallus to an apparently female phallus, depending on the degree of androgen action (49). However, the fundamental finding from the present studies is that androgen action before E19.5 in rats is vital to induce penis formation and that androgen action after this age cannot result in normal penis formation, even though it can modify phallus size.…”

Section: Figuresupporting

confidence: 69%

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Welsh¹,

Saunders²,

Fisken³

et al. 2008

J. Clin. Invest.

651

632

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Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8-14 weeks of gestation.

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Section: Figuresupporting

confidence: 69%

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Welsh¹,

Saunders²,

Fisken³

et al. 2008

J. Clin. Invest.

651

632

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“…9 Recently, the sex hormone-binding globulin test has been shown to provide functional information about the severity of the receptor defect. 10 These tests are unfortunately not available at our hospital.…”

Section: Discussionmentioning

confidence: 98%

Male Pseudohermaphroditism: Etiological Evaluation, Surgical Treatment, and the Incidencein Relation to Inguinal Hernia

Al-Salem

Abusrair

2000

Ann Saudi Med

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“…The considerable variability in the degree of impaired AR activity accounts for the wide clinical spectrum of external undervirilisation observed in PAIS (73). Wolffian duct structures may be partly or entirely present.…”

Section: Molecular Mechanisms Of Androgen Actionmentioning

confidence: 99%

The molecular basis of male sexual differentiation

Hiort

Holterhus

2000

European Journal of Endocrinology

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Male sexual differentiation is the result of complex mechanisms involving developmental genetics and endocrinology. Formation of the bipotential gonads and subsequently the testes is dependent on a series of sex chromosome-linked and autosomal genes. The testes secrete both peptide and steroid hormones essential for the formation of internal and external genitalia. Hormone action is mediated via specific receptors, functioning as transcription regulators. Disruption of these genetic events leads to sexual dimorphism involving external and internal genitalia, and may also interfere with the development of other organs.

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Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene

Cited by 119 publications

References 30 publications

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Male Pseudohermaphroditism: Etiological Evaluation, Surgical Treatment, and the Incidencein Relation to Inguinal Hernia

The molecular basis of male sexual differentiation

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