Complete androgen insensitivity without Wolffian duct development: the AR‐A form of the androgen receptor is not sufficient for male genital development

Barbaro, Michela; Oscarson, Mikael; Almskog, Ingrid; Hamberg, Hans; Wedell, Anna

doi:10.1111/j.1365-2265.2007.02819.x

Cited by 7 publications

(2 citation statements)

References 23 publications

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“…This structure may be comparable to Wolffian duct structures in mammals, however these structures are of different embryological origins and may be analogous in function alone (Shaw andRenfree, 2014, Matthews et al, 2018). Nevertheless, both structures appear to be highly dependent on androgens for their development, as abnormal Wolffian duct structures are frequently seen in complete androgen insensitivity syndrome (Hannema et al, 2006, Barbaro et al, 2007. Wolffian duct structures are also absent in AR knock-out mice (Yeh et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

11β-Hydroxylase loss disrupts steroidogenesis and reproductive function in zebrafish

Oakes

Barnard

Storbeck

et al. 2020

Journal of Endocrinology

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The roles of androgens in male reproductive development and function in zebrafish are poorly understood. To investigate this topic we employed CRISPR/Cas9 to generate cyp11c1 (11β-hydroxylase) mutant zebrafish lines. Our study confirms recently published findings from a different cyp11c1-/- mutant zebrafish line, and also reports novel aspects of the phenotype caused by loss of Cyp11c1 function. We report that Cyp11c1-deficient zebrafish display predominantly female secondary sex characteristics, but may possess either ovaries or testes. Moreover, we observed that cyp11c1-/- mutant male zebrafish are profoundly androgen- and cortisol-deficient. These results provide further evidence that androgens are dispensable for testis formation in zebrafish, as has been demonstrated previously in androgen-deficient and androgen-resistant zebrafish. Herein, we show that the testes of cyp11c1-/- mutant zebrafish exhibit a disorganised tubular structure; and for the first time demonstrate that the spermatic ducts, which connect the testes to the urogenital orifice, are severely hypoplastic in androgen-deficient zebrafish. Furthermore, we show that spermatogenesis and characteristic breeding behaviours are impaired in cyp11c1-/- mutant zebrafish. Expression of nanos2, a type A spermatogonia marker, was significantly increased in the testes of Cyp11c1-deficient zebrafish, whereas expression of markers for later stages of spermatogenesis was significantly decreased. These observations indicate that in zebrafish, production of type A spermatogonia is androgen-independent, but differentiation of type A spermatogonia is an androgen-dependent process. Overall, our results demonstrate that whilst androgens are not required for testis formation, they play important roles in determining secondary sexual characteristics, proper organisation of seminiferous tubules, and differentiation of male germ cells.

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Section: Discussionmentioning

confidence: 99%

11β-Hydroxylase loss disrupts steroidogenesis and reproductive function in zebrafish

Oakes

Barnard

Storbeck

et al. 2020

Journal of Endocrinology

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“…The cells have to be increased in number by culturing through several passages in tissue culture before these experiments can be undertaken. Receptor gene analysis is available in a few centres (155, 156, 157, 158, 159). Increased ratios of 5α to 5β reduced androgens have been found in association with Serkal syndrome (sex reversal with dysgenesis of kidneys, adrenals and lungs) possibly reflecting increased 5α−reductase and loss of function of WNT4 signalling (160).…”

Section: Androgen Deficiencymentioning

confidence: 99%

Diagnosis of Diseases of Steroid Hormone Production, Metabolism and Action

Honour¹

2009

JCRPE

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Biochemical tests have been the basis for investigations of disorders affecting steroid hormones. In recent years it has been possible however to study the genes that determine functional enzymes, cofactors, receptors, transcription factors and signaling systems that are involved in the process. Analyses of mutations are available as a diagnostic service for only a few of these genes although research laboratories may be able to provide a service. Both biochemical and genetic research have brought to light new disorders. Some genes for transcription factors involved in the development of the endocrine organs have also been identified and patients with defects in these processes have been found. This paper will review general aspects of adrenal disorders with emphasis on clinical and laboratory findings. As with all endocrine investigations there are few single measurements that provide a definitive answer to a diagnosis. Timing of samples in relation to age, gender and time of day needs to be considered.Conflict of interest:None declared.

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Genetic Defects of Androgen Resistance

Qin

2010

Genetic Diagnosis of Endocrine Disorders

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Complete androgen insensitivity without Wolffian duct development: the AR‐A form of the androgen receptor is not sufficient for male genital development

Abstract: The presence of the AR-A form does not seem to be sufficient for WD maintenance and differentiation.

Cited by 7 publications

References 23 publications

11β-Hydroxylase loss disrupts steroidogenesis and reproductive function in zebrafish

11β-Hydroxylase loss disrupts steroidogenesis and reproductive function in zebrafish

Diagnosis of Diseases of Steroid Hormone Production, Metabolism and Action

Genetic Defects of Androgen Resistance

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