Identification of an Enhancer in the Ad4BP/SF-1 Gene Specific for Fetal Leydig Cells

Shima, Yuichi; Miyabayashi, Kanako; Baba, Takashi; Okada, H.; Oka, Sanae; Zubair, Mohamad; Morohashi, Ken Ichirou

doi:10.1210/en.2011-1407

Cited by 51 publications

(52 citation statements)

References 38 publications

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“…3, Hypothesis 2). Studies using genetic mouse assays to trace FLCs from fetal to adult testes specifically have yielded new insights on the FLC fate [10,11,49]. The adrenal 4 binding protein/steroidogenic factor 1 (Ad4BP/SF1), also known as NR5A1, is expressed in both FLCs and ALCs and it is crucial for their development and steroidogenesis [50].…”

Section: Flc Cytogenesismentioning

confidence: 99%

Development, function and fate of fetal Leydig cells

Wen

Cheng

Liu

2016

Seminars in Cell & Developmental Biology

108

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During fetal testis development, fetal Leydig cells (FLCs) are found to be originated from multiple progenitor cells. FLC specification and function are under tight regulation of specific genes and signaling proteins. Furthermore, Sertoli cells play a crucial role to regulate FLC differentiation during fetal testis development. FLC progenitor- and FLC-produced biomolecules are also involved in the differentiation and activity of rodent FLCs. The main function of FLCs is to produce androgens to masculinize XY embryos. However, FLCs are capable of producing androstenedione but not testosterone due to the lack of 17β-HSD (17β-hydroxysteroid dehydrogenase), but fetal Sertoli cells express 17β-HSD which thus transforms androstenedione to testosterone in the fetal testis. On the other hand, FLCs produce activin A to regulate Sertoli cell proliferation, and Sertoli cells in turn modulate testis cord expansion. It is now generally accepted that adult Leydig cells (ALCs) gradually replace FLCs during postnatal development to produce testosterone to support spermatogenesis as FLCs undergo degeneration in neonatal and pre-pubertal testes. However, based on studies using genetic tracing mouse models, FLCs are found to persist in adult testes, making up ~20% of total Leydig cells. In this review, we evaluate the latest findings regarding the development, function and fate of FLCs during fetal and adult testis development.

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Section: Flc Cytogenesismentioning

confidence: 99%

Development, function and fate of fetal Leydig cells

Wen

Cheng

Liu

2016

Seminars in Cell & Developmental Biology

108

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“…We previously established transgenic mice ( FLE-EGFP mice) using the fetal Leydig enhancer ( FLE ) and the upstream region of the Ad4BP/Sf-1 gene [Shima et al, 2012]. These mice provided us with weakly EGFP-labeled cells in addition to strongly EGFP-labeled FLCs .…”

Section: Gene Expression Of Flcs Altering With Developmentmentioning

confidence: 99%

Alterations in Fetal Leydig Cell Gene Expression during Fetal and Adult Development

Miyabayashi

Shima

Inoue³

et al. 2016

Sex Dev

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Fetal Leydig cells (FLCs) and adult Leydig cells (ALCs) develop in the mammalian prenatal and postnatal testes, respectively. In mice, FLCs emerge in the interstitial space of the testis as early as embryonic day 12.5 and thereafter increase in number during the fetal stage. We previously established a transgenic mouse line in which FLCs are labeled with EGFP and demonstrated that the EGFP-labeled FLCs were present even in adult testes. However, the characteristics of FLCs during postnatal stages remained unclear. In the present study, a comparison of the transcriptomes of FLCs from prenatal and postnatal testes and of ALCs from adult testes revealed that FLCs gradually alter their characteristics across developmental stages and come to roughly resemble ALCs. Many cholesterogenic genes simultaneously expressed a unique alternation pattern, while many oxidative phosphorylation and β-oxidation (both mitochondrial functions) genes showed a different unique pattern. These metabolic gene expression alterations might be triggered by milieu changes, such as nutrient and oxygen supply, from the prenatal to the postnatal period.

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“…Steroidogenic cells in the adrenal cortex and gonads arise from a common pool of progenitors in the adrenogonadal primordia, but the mechanisms that determine whether a given precursor cell adopts an adrenocortical or gonadal phenotype are not fully understood (Val et al, 2006; Hu et al, 2007; Morohashi and Zubair, 2011; Wood and Hammer, 2011; Laufer et al, 2012; Shima et al, 2012; Simon and Hammer, 2012; Bandiera et al, 2013; Pihlajoki et al, 2013b; Wood et al, 2013). One experimentally tractable model for the study of steroidogenic cell fate determination is gonadectomy (GDX)-induced adrenocortical neoplasia.…”

Section: Introductionmentioning

confidence: 99%

Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret

Schillebeeckx

Pihlajoki

Gretzinger

et al. 2015

Molecular and Cellular Endocrinology

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Gonadectomy (GDX) induces sex steroid-producing adrenocortical tumors in certain mouse strains and in the domestic ferret. Transcriptome analysis and DNA methylation mapping were used to identify novel genetic and epigenetic markers of GDX-induced adrenocortical neoplasia in female DBA/2J mice. Markers were validated using a combination of laser capture microdissection, quantitative RT-PCR, in situ hybridization, and immunohistochemistry. Microarray expression profiling of whole adrenal mRNA from ovariectomized vs. intact mice demonstrated selective upregulation of gonadal-like genes including Spinlw1 and Insl3 in GDX-induced adrenocortical tumors of the mouse. A complementary candidate gene approach identified Foxl2 as another gonadal-like marker expressed in GDX-induced neoplasms of the mouse and ferret. That both “male-specific” (Spinlw1) and “female-specific” (Foxl2) markers were identified is noteworthy and implies that the neoplasms exhibit mixed characteristics of male and female gonadal somatic cells. Genome-wide methylation analysis showed that two genes with hypomethylated promoters, Igfbp6 and Foxs1, are upregulated in GDX-induced adrenocortical neoplasms. These new genetic and epigenetic markers may prove useful for studies of steroidogenic cell development and for diagnostic testing.

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Identification of an Enhancer in the Ad4BP/SF-1 Gene Specific for Fetal Leydig Cells

Cited by 51 publications

References 38 publications

Development, function and fate of fetal Leydig cells

Development, function and fate of fetal Leydig cells

Alterations in Fetal Leydig Cell Gene Expression during Fetal and Adult Development

Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret

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