Relationship of a Mouse Sertoli Cell Line (MSC-1) to Normal Sertoli Cells1

McGuinness, Michael; Linder, C.; Morales, Carlos R.; Heckert, Leslie L.; Pikus, Jeremie; Griswold, Michael D.

doi:10.1095/biolreprod51.1.116

Cited by 78 publications

(45 citation statements)

References 39 publications

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“…SC-line MSC-1 was kindly donated by Michael D. Griswold (Washington State University, Pullman, WA). MSC-1 cells were grown as described previously (27). For mice SC primary cultures, a protocol was adapted from Karl and Griswold (19).…”

Section: Methodsmentioning

confidence: 99%

Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload

Leichtmann‐Bardoogo

Cohen

Weiss

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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The universal importance of iron, its high toxicity, and complex chemistry present a challenge to biological systems in general and to protected compartments in particular. The high mitotic rate and avid mitochondriogenesis of developing male germ cells imply high iron requirements. Yet access to germ cells is tightly regulated by the blood-testis barrier that protects the meiotic and postmeiotic germ cells. To elucidate how iron is supplied to developing male germ cells, we analyzed iron deposition and iron transport proteins in testes of mice with iron overload and with genetic ablation of the iron regulators Hfe and iron regulatory protein 2. Iron accumulated mainly around seminiferous tubules, and only small amounts localized within the seminiferous tubules. The localization and regulation of proteins involved in iron import, storage, and export such as transferrin, transferrin receptor, the divalent metal transporter-1, cytosolic ferritin, and ferroportin strongly support a model of a largely autonomous iron cycle within seminiferous tubules. We show evidence that ferritin secretion from Sertoli cells may play an important role in iron acquisition of primary spermatocytes. During spermatogenic development iron is carried along from primary spermatocytes to spermatids, and from spermatids iron is recycled to the apical compartment of Sertoli cells, which traffic it back to a new generation of spermatocytes. Losses are replenished by the peripheral circulation. Such an internal iron cycle essentially detaches the iron homeostasis within the seminiferous tubule from the periphery and protects developing germ cells from iron fluctuations. This model explains how compartmentalization can optimize cellular and systemic nutrient homeostasis.

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Section: Methodsmentioning

confidence: 99%

Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload

Leichtmann‐Bardoogo

Cohen

Weiss

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…The first implication that the E-box and Usf proteins functioned in vivo came from epigenetic studies showing that global demethylation of cells in culture resulted in activation of the normally silent Fshr gene, which correlated with binding status of the E-box (McGuinness et al, 1994;Griswold and Kim, 2001). Additional evidence from in vivo genomic footprinting demonstrated the E-box was bound by proteins in Sertoli cells, but not in non-expressing cells, indicating that, within the endogenous gene's promoter, the E-box is occupied and thus functional only in expressing cells (Heckert et al, 2000).…”

Section: The E-box and Usf Are Central To Fshr Transcriptionmentioning

confidence: 99%

Transcriptional regulation of the FSH receptor: New perspectives

Hermann

Heckert

2007

Molecular and Cellular Endocrinology

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The cell-surface receptor for the gonadotropin follicle-stimulating hormone (FSH) is expressed exclusively on Sertoli cells of the testis and granulosa cells of the ovary. FSH signal transduction through its receptor (Fshr) is critical for the timing and maintenance of normal gametogenesis in the mammalian gonad. In the 13 years since the gene encoding Fshr was first cloned, the mechanisms controlling its transcription have been extensively examined, but a clear understanding of what drives its unique cell-specificity remains elusive. Current knowledge of basal Fshr transcription highlights the role of an E-box in the proximal promoter which is bound by the basic helix-loop-helix transcription factors upstream stimulatory factor 1 (Usf1) and Usf2. Recent studies utilizing knockout mice and chromatin immunoprecipitation validated the importance of Usf to Fshr transcription and demonstrated a sexually dimorphic requirement for the Usf proteins to maintain normal Fshr expression. Studies have also shown that the promoter region itself is insufficient for appropriate Fshr expression in transgenic mice, indicating Fshr transcription depends on regulatory elements that lie outside of the promoter. Identification of such elements has been propelled by recent availability of genome sequence data, which facilitated studies using comparative genomics, DNase I hypersensitivity mapping, and transgenic analysis with large fragments of DNA. This review will focus on the current understanding of transcriptional regulatory processes that control expression of rat Fshr, including recent advances from our laboratory.

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“…The core promoter of the rat FSHR gene does not contain CpG islands but does contain a few specific CpG dinucleotides that are potential methylation sites (Heckert et al, 1992). Using bisulfite-based DNA sequencing, seven specific CpG sites within the FSHR core promoter were shown to be methylated in cells that did not express the gene and unmethylated in Sertoli cells (Figure 2) (McGuinness et al, 1994;Griswold and Kim, 2001).…”

Section: Role Of Methylation and Chromatin Structure In Fshr Exprmentioning

confidence: 99%

“…In addition, the mouse Sertoli cell line (MSC-1) derived from a testicular tumor has an inactive FSHR promoter (McGuinness et al, 1994) and the inactive state of transcription in MSC-1 cells correlated with the cytosine methylation of the core promoter of the FSHR gene (Griswold and Kim, 2001). Treatment of MSC-1 cells with 5-azacytidine (5-azaCdR) resulted in the demethylation of the mouse FSHR promoter and reactivated the transcription of the FSHR gene.…”

Section: Role Of Methylation and Chromatin Structure In Fshr Exprmentioning

confidence: 99%

The Expression of the Follicle-stimulating Hormone Receptor in Spermatogenesis

Heckert

Griswold²

2002

Recent Progress in Hormone Research

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Results from experiments using mouse models suggest that the role of follicle-stimulating hormone (FSH) in spermatogenesis is the regulation of Sertoli cell proliferation and, ultimately, the size and spermatogenic capacity of the testis. The regulation of the expression of the FSH receptor (FSHR) gene is very cell specific and plays an initial role in the ultimate response of the Sertoli cells to FSH. The extreme cell specificity and the importance of the FSH response to spermatogenesis have led to an extensive characterization of the promoter of the FSHR gene. Several widely expressed transcription factors -including USF 1 and 2, GATA-1, and SF-1 and potential elements such as an E2F site and an Inr region -have been shown to contribute to the maximal transcription of the transfected FSHR gene. However, these experiments have failed to provide clues as to the cell-specific expression of the FSHR gene. In both cell transfections and in transgenic mice, the promoter can direct expression of transgenes promiscuously. The rodent FSHR promoter contains conserved CpG dinucleotides that were shown to be methylated in nonexpressing cells and tissue but unmethylated in Sertoli cells. The methylated CpG sites could interfere with the binding of general transcription factors and/or lead to a repressive chromatin structure in the nonexpressing cells. While yet-undiscovered cell-specific factors may play a role in the expression of the FSHR gene, repression and activation of local chromatin structure are likely to be involved. I. Biology of the Follicle-stimulating Hormone (FSH) Receptor in SpermatogenesisThe primary hormonal controls on spermatogenesis involve the action of FSH and testosterone on Sertoli cells. Many of the studies examining the actions of FSH have been done on cultured Sertoli cells from 10-to 30-day-old rats. The Sertoli cells from rats of this age are easily placed in culture and respond to FSH with increased levels of cyclic AMP (cAMP), increased protein synthesis, and increased estradiol production (Fritz et al., 1976). As the age of the rat increases to 40 days or more, the response of Sertoli cells both in culture and in vivo changes. There is a large increase in the phosphodiesterase activity in the cells and the accumulation of cAMP and the subsequent stimulation of specific protein 129

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Relationship of a Mouse Sertoli Cell Line (MSC-1) to Normal Sertoli Cells1

Cited by 78 publications

References 39 publications

Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload

Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload

Transcriptional regulation of the FSH receptor: New perspectives

The Expression of the Follicle-stimulating Hormone Receptor in Spermatogenesis

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