title: Transcriptional regulation of genes related to progesterone production.
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 proliferator-activated 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.
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizutani
authors.forename: Shin
authors.initials: S
authors.lastname: Ishikane
authors.forename: Shinya
authors.initials: S
authors.lastname: Kawabe
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics; D011374:Progesterone / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D054339:Steroidogenic Factor 1 / Q000235:genetics; D014158:Transcription, Genetic; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C515057:NR5A1 protein, human; D010750:Phosphoproteins; D054339:Steroidogenic Factor 1; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D005982:Glutathione Transferase