Both Testosterone and Follicle-Stimulating Hormone Independently Inhibit Spermatogonial Differentiation in Irradiated Rats

Shetty, Gunapala; Weng, Connie C.; Meachem, Sarah J; Bolden-Tiller, Olga; Zhang, Zhen; Pakarinen, Pirjo; Huhtaniemi, Ilpo; Meistrich, Marvin L.

doi:10.1210/en.2005-0984

Cited by 32 publications

(33 citation statements)

References 39 publications

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“…Rat serum FSH and LH levels were measured using immunofluorometric assays (Delfia; PerkinElmer Wallac) [22,23,29,30]. Serum E2 was measured using an anti-E2 antibody, double-antibody radioimmunoassay kit (catalog no.…”

Section: Hormone Measurementsmentioning

confidence: 99%

“…However, this block was slowly reversed by treatment with GnRH-ant and flutamide, which suppresses intratesticular testosterone (ITT) and gonadotropin levels and inhibits testosterone action [21,22]. Further studies showed that ITT (and, to a lesser extent, FSH) primarily was responsible for the inhibition of differentiation in this system [23].…”

Section: Introductionmentioning

confidence: 99%

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Estrogen-Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation1

Zhou¹,

Bolden-Tiller²,

Shao³

et al. 2011

Biology of Reproduction

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Despite numerous observations of the effects of estrogens on spermatogenesis, identification of estrogen-regulated genes in the testis is limited. Using rats in which irradiation had completely blocked spermatogonial differentiation, we previously showed that testosterone suppression with gonadotropin-releasing hormone-antagonist acyline and the antiandrogen flutamide stimulated spermatogenic recovery and that addition of estradiol (E2) to this regimen accelerated this recovery. We report here the global changes in testicular cell gene expression induced by the E2 treatment. By minimizing the changes in other hormones and using concurrent data on regulation of the genes by these hormones, we were able to dissect the effects of estrogen on gene expression, independent of gonadotropin or testosterone changes. Expression of 20 genes, largely in somatic cells, was up- or downregulated between 2- and 5-fold by E2. The unexpected and striking enrichment of transcripts not corresponding to known genes among the E2-downregulated probes suggested that these might represent noncoding mRNAs; indeed, we have identified several as miRNAs and their potential target genes in this system. We propose that genes for which expression levels are altered in one direction by irradiation and in the opposite direction by both testosterone suppression and E2 treatment are candidates for controlling the block in differentiation. Several genes, including insulin-like 3 (Insl3), satisfied those criteria. If they are indeed involved in the inhibition of spermatogonial differentiation, they may be candidate targets for treatments to enhance recovery of spermatogenesis following gonadotoxic exposures, such as those resulting from cancer therapy.

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Section: Hormone Measurementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estrogen-Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation1

Zhou¹,

Bolden-Tiller²,

Shao³

et al. 2011

Biology of Reproduction

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show abstract

“…However, recovery of spermatogonial proliferation is blocked by testosterone following cytotoxic damage to the testis in rats from multiple toxicants including radiation (Meistrich & Shetty 2003, Shetty et al 2006a. In addition, FSH also blocks spermatogonial proliferation independently of testosterone following irradiation.…”

Section: Testosterone Regulation Of Spermatogoniamentioning

confidence: 99%

Maintaining the male germline: regulation of spermatogonial stem cells

Caires

Broady²,

McLean

2010

Journal of Endocrinology

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Spermatogonial stem cells (SSCs) are a self-renewing population of adult stem cells capable of producing progeny cells for sperm production throughout the life of the male. Regulation of the SSC population includes establishment and maintenance of a niche microenvironment in the seminiferous tubules of the testis. Signaling from somatic cells within the niche determines the fate of SSCs by either supporting self-renewal or initiating differentiation leading to meiotic entry and production of spermatozoa. Despite the importance of these processes, little is known about the biochemical and cellular mechanisms that govern SSC fate and identity. This review discusses research findings regarding systemic, endocrine, and local cues that stimulate somatic niche cells to produce factors that contribute to the homeostasis of SSCs in mammals. In addition to their importance for male fertility, SSCs represent a model for the investigation of adult stem cells because they can be maintained in culture, and the presence, proliferation, or loss of SSCs in a cell population can be determined with the use of a transplantation assay. Defining the mechanisms that regulate the self-renewal and differentiation of SSCs will fundamentally improve the understanding of male fertility and provide information about the regulation of adult stem cells in other tissues.

show abstract

Section: Hormone Measurementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estrogen Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation.

Zhou

Bolden-Tiller

Shao

et al. 2011

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

Despite numerous observations of the effects of estrogens on spermatogenesis, identification of estrogen-regulated genes in the testis is limited. Using rats in which irradiation had completely blocked spermatogonial differentiation, we previously showed that testosterone suppression with gonadotropinreleasing hormone-antagonist acyline and the antiandrogen flutamide stimulated spermatogenic recovery and that addition of estradiol (E2) to this regimen accelerated this recovery. We report here the global changes in testicular cell gene expression induced by the E2 treatment. By minimizing the changes in other hormones and using concurrent data on regulation of the genes by these hormones, we were able to dissect the effects of estrogen on gene expression, independent of gonadotropin or testosterone changes. Expression of 20 genes, largely in somatic cells, was up-or downregulated between 2-and 5-fold by E2. The unexpected and striking enrichment of transcripts not corresponding to known genes among the E2-downregulated probes suggested that these might represent noncoding mRNAs; indeed, we have identified several as miRNAs and their potential target genes in this system. We propose that genes for which expression levels are altered in one direction by irradiation and in the opposite direction by both testosterone suppression and E2 treatment are candidates for controlling the block in differentiation. Several genes, including insulin-like 3 (Insl3), satisfied those criteria. If they are indeed involved in the inhibition of spermatogonial differentiation, they may be candidate targets for treatments to enhance recovery of spermatogenesis following gonadotoxic exposures, such as those resulting from cancer therapy.

show abstract

Both Testosterone and Follicle-Stimulating Hormone Independently Inhibit Spermatogonial Differentiation in Irradiated Rats

Cited by 32 publications

References 39 publications

Estrogen-Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation1

Estrogen-Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation1

Maintaining the male germline: regulation of spermatogonial stem cells

Estrogen Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation.

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