Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids

Holdcraft, Robert W.; Braun, Robert E.

doi:10.1242/dev.00957

Cited by 409 publications

(337 citation statements)

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“…In sexually mature mice, the androgen receptor (Ar) is expressed in Sertoli cells in a stage-dependent pattern (8), and androgen withdrawal experiments support the notion that androgens exert their influence during the stages of highest androgen receptor expression (9)(10)(11). Sertoli cell-specific ablation of the gene encoding the androgen receptor indicates that androgens are required for progression of germ cells through meiosis I, again during the transition from round to elongating spermatids, and finally during the terminal stages of spermiogenesis (12)(13)(14).…”

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confidence: 99%

Androgens regulate the permeability of the blood–testis barrier

Meng

Holdcraft

Shima

et al. 2005

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

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Within the mammalian testis, specialized tight junctions between somatic Sertoli cells create basal and apical polarity within the cells, restrict movement of molecules between cells, and separate the seminiferous epithelium into basal and adluminal compartments. These tight junctions form the basis of the blood-testis barrier, a structure whose function and dynamic regulation is poorly understood. In this study, we used microarray gene expression profiling to identify genes with altered transcript levels in a mouse model for conditional androgen insensitivity. We show that testosterone, acting through its receptor expressed in Sertoli cells, regulates the expression of claudin 3, which encodes a transient component of newly formed tight junctions. Sertoli cell-specific ablation of androgen receptor results in increased permeability of the bloodtestis barrier to biotin, suggesting claudin 3 regulates the movement of small molecules across the Sertoli cell tight junctions. These results suggest that androgen action in Sertoli cells regulates germ cell differentiation, in part by controlling the microenvironment of the seminiferous epithelium. Our studies also indicate that hormonal strategies for male contraception may interfere with the blood-testis barrier.androgen receptor ͉ testosterone ͉ tight junctions

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confidence: 99%

Androgens regulate the permeability of the blood–testis barrier

Meng

Holdcraft

Shima

et al. 2005

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

Self Cite

362

348

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“…The subject of this paper is the Pp, a cell-type-specific promoter that we previously demonstrated is expressed exclusively in Sertoli cells and caput epididymal cells in both mice and rats (38,51,59). Its expression in both of these cell types depends on testosterone and the nuclear hormone receptor androgen receptor (AR) (10,25,37,38,51,59). In Sertoli cells, the Pp is dramatically induced between postnatal day 8 (P8) and P9, the time point when adjacent germ cells enter the preleptotene stage of meiosis (37).…”

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confidence: 99%

GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

Bhardwaj

Rao

Kaur

et al. 2008

Molecular and Cellular Biology

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How Sertoli-specific expression is initiated is poorly understood. Here, we address this issue using the proximal promoter (Pp) from the Rhox5 homeobox gene. Its Sertoli cell-specific expression is achieved, in part, through a negative regulatory element that inhibits Pp transcription in non-Sertoli cell lines. Complementing this negative regulation is positive regulation conferred by four androgen-response elements (AREs) that interact with the androgen receptor (AR), a nuclear hormone receptor expressed at high levels in Sertoli cells. A third control mechanism is provided by a consensus GATA-binding site that is crucial for Pp transcription both in vitro and in vivo. Several lines of evidence suggested that GATA factors and AR act cooperatively to activate Pp transcription: (i) the GATA-binding site crucial for Pp transcription is in close proximity to two of the AREs, (ii) GATA and AR form a complex with the Pp in vitro, (iii) overexpression of GATA factors rescued expression from mutant Pp constructs harboring defective AREs, and (iv) incubation of a Sertoli cell line with testosterone triggered corecruitment of AR and GATA4 to the Pp. Collectively, our results suggest that the Rhox5 gene achieves Sertoli cell-specific transcription using a combinatorial strategy involving negative and cooperative positive regulation.

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“…Sertoli cells, such as ERM, Claudin 11 and Androgen Receptor (AR) [80][81][82]. Furthermore, transplantation of functioning Sertoli cells in a mouse can recover fertility in mice with genetic Sertoli cell defects [83].…”

Section: Regulation Of Spermatogonial Stem Cellsmentioning

confidence: 99%