Transcriptional regulation of human ferredoxin reductase through an intronic enhancer in steroidogenic cells

Imamichi, Yoshitaka; Mizutani, Tetsuya; Ju, Young‐Tae; Matsumura, Takeshi; Kawabe, Shinya; Kanno, Masafumi; Yazawa, Takashi; Miyamoto, Kaoru

doi:10.1016/j.bbagrm.2013.11.005

Cited by 23 publications

(19 citation statements)

References 31 publications

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“…Using these cells, novel SF-1/Ad4BP-regulated genes, including 5-aminolevulinic acid synthase 1 [60], ferredoxin 1 [61], ferredoxin reductase [62], glutathione S-transferase A family [63] and ovarian isoform of LRH-1 [20] have been identified by combined DNA microarray and promoter tiling array analyses. In adrenal and gonadal steroidogenic cells, expression of these genes is regulated by direct binding of SF-1/Ad4BP to the promoter and enhancer regions.…”

Section: Steroidogenic Cells Derived From Various Mscs and Their Propmentioning

confidence: 99%

Induction of steroidogenic cells from adult stem cells and pluripotent stem cells [Review]

et al. 2016

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Abstract. Steroid hormones are mainly produced in adrenal glands and gonads. Because steroid hormones play vital roles in various physiological processes, replacement of deficient steroid hormones by hormone replacement therapy (HRT) is necessary for patients with adrenal and gonadal failure. In addition to HRT, tissue regeneration using stem cells is predicted to provide novel therapy. Among various stem cell types, mesenchymal stem cells can be differentiated into steroidogenic cells following ectopic expression of nuclear receptor (NR) 5A subfamily proteins, steroidogenic factor-1 (also known as adrenal 4 binding protein) and liver receptor homolog-1, with the aid of cAMP signaling. Conversely, these approaches cannot be applied to pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, because of poor survival following cytotoxic expression of NR5A subfamily proteins. However, if pluripotent stem cells are first differentiated through mesenchymal lineage, they can also be differentiated into steroidogenic cells via NR5A subfamily protein expression. This approach offers a potential suitable cells for future regenerative medicine and gene therapy for diseases caused by steroidogenesis deficiencies. It represents a powerful tool to investigate the molecular mechanisms involved in steroidogenesis. This article highlights our own and current research on the induction of steroidogenic cells from various stem cells. We also discuss the future direction of their clinical application.Key words: Steroid hormone, Steroidogenic factor-1/adrenal 4 binding protein, Liver receptor homolog-1, Stem cells, Transcription STEROID hormones play essential roles in various physiological processes, such as glucose metabolism, stress response, fluid and electrolyte balance, sex differentiation, reproduction and sexual behavior. Steroid hormones are synthesized from cholesterol predominantly in the adrenal glands and gonads [1]. Dysfunction of these organs often cause deficiency in steroidogenesis, whereas patients suffer from painful and sometimes life-threatening conditions in the absence of hormone replacement [2][3][4][5][6]. Although hormone replacement therapy (HRT) well-established for treatment of these patients, the HRT is required throughout their life with the increased incidence of serious side effects. It is hoped that stem cell-based regenerative medicine will provide novel therapies for resolving these issues. Stem cell-derived steroidogenic cells could restore the normal function of intrinsic organs following their transplantation. Consequently, induction of steroidogenic cells from stem cells represents an essential first-step in achieving this therapeutic goal. In addition, stem cell-derived steroidogenic cells provide a powerful tool to study the development and function of steroidogenic cells, because they reflect the intrinsic cell's developmental processes and characteristics. In this article, we describe our research and that of other groups for the induction of steroidogenic c...

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Section: Steroidogenic Cells Derived From Various Mscs and Their Propmentioning

confidence: 99%

Induction of steroidogenic cells from adult stem cells and pluripotent stem cells [Review]

et al. 2016

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“…Consistent with this hypothesis, SF-1/ Ad4BP regulates the transcription of all cytochrome P450 steroid hydroxylase genes (Carlone and Richards, 1997;Guo et al, 2003;Hanley et al, 2001;Hu et al, 2001;Lala et al, 1992;Lin et al, 2001;Lynch et al, 1993;Michael et al, 1995;Morohashi et al, 1993;Schimmer and Parker, 1992;Wang et al, 2000;Ye et al, 2009;Zhang and Mellon, 1996) (Table 1). Additionally, the transcription of various steroidogenesis-related genes is regulated by SF-1/Ad4BP, such as cholesterol deliverers (Cao et al, 1997;Caron et al, 1997; Sugawara et al, 1996), hydroxysteroid dehydrogenase (Leers-Sucheta et al, 1997), and electron transporters (Huang et al, 2005;Imamichi et al, 2013Imamichi et al, , 2014 (Table 1). LRH-1 was first discovered in mouse liver as a transcription factor that regulates the transcription of α-fetoprotein (Becker-Andre et al, 1993;Galarneau et al, 1996).…”

Section: General Characteristics Of Sf-1 and Lrh-1mentioning

confidence: 99%

Regulation of Steroidogenesis, Development, and Cell Differentiation by Steroidogenic Factor-1 and Liver Receptor Homolog-1

et al. 2015

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“…Indeed, ALAS1 and FDXR expression was increased by members of the NR5A family through its binding to the ~3.5 kb upstream and the second intronic region, respectively. H3K4me2 accumulation was observed within these regions in steroidogenic cells [11,12]. Transcription of FDX1 was synergistically activated by the members of the NR5A family and a cyclic AMPresponsive element (CRE)-binding protein (CREB) through their binding sites in the promoter [10].…”

Section: Othersmentioning

confidence: 95%

“…Human glutathione S-transferases (hGST) A1-1 and A3-3, 5-aminolevulinic acid synthase 1 (ALAS1), ferredoxin 1 (FDX1), and ferredoxin reductase (FDXR) were identified as steroidogenesis-related proteins [10][11][12][13].…”

Section: Othersmentioning

confidence: 99%

“…Several reports, including ours, have previously described that introduction of members of the NR5A family into mesenchymal stem cells resulted in the differentiation of the cells into a steroidogenic cell lineage [6][7][8][9]. Taking advantage of the differentiation system, we characterized cis-and trans-acting regulators involved in the transcription of genes related to progesterone production [10][11][12][13][14][15]. In this review, we describe the cis-and trans-acting regulators and their effects on the genes related to the production of progesterone.…”

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Transcriptional regulation of genes related to progesterone production [Review]

et al. 2015

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Abstract. Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase/Δ 5 -Δ 4 isomerase (3β-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert Δ 5 -Δ 4 isomerization activity to produce progesterone in a cooperative fashion with 3β-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferatoractivated receptor-γ coactivator-1α (PGC-1α), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/ enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production.

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Transcriptional regulation of human ferredoxin reductase through an intronic enhancer in steroidogenic cells

Cited by 23 publications

References 31 publications

Induction of steroidogenic cells from adult stem cells and pluripotent stem cells [Review]

Induction of steroidogenic cells from adult stem cells and pluripotent stem cells [Review]

Regulation of Steroidogenesis, Development, and Cell Differentiation by Steroidogenic Factor-1 and Liver Receptor Homolog-1

Transcriptional regulation of genes related to progesterone production [Review]

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