title: Luteinizing hormone (LH) regulates production of androstenedione and progesterone via control of histone acetylation of StAR and CYP17 promoters in ovarian theca cells.
abstract: Although luteinizing hormone (LH) affects androstenedione (A4) and progesterone (P4) production in theca cells, it is still unknown how LH influences molecular mechanism of A4 and P4 production. To examine the relationship between LH and transcription factors involved in A4 and P4 production, ovarian theca cells were cultured in the presence or absence of high concentrations of LH for 24 h (pre-treatment with high concentration of LH) and then cultured in the presence or absence of low concentration of LH for 48 h. Low LH enhanced production of A4 and P4, and expressions of CYP17 and StAR mRNA in theca cells without pre-treatment with high LH. In addition, low LH stimulated the expression of SF-1 protein in nuclear fractions from theca cells with or without pre-treatment with high LH. The binding of SF-1 to the CYP17 and StAR promoter regions increased in theca cells treated with low LH. Although GATA-4 and GATA-6 are both found in the nuclear fraction but not in the cytosol of theca cells, low LH enhanced the binding of GATA-6, but not of GATA-4, to the CYP17 promoter region without pre-treatment with high LH. Acetylation histone H3 in StAR and CYP17 promoter regions were changed by different LH-dosage. Overall, we showed that LH regulates the production of A4 and P4 by affecting the nuclear localization and switching of transcription factors in theca cells and that target transcription factors involved in steroid production in theca cells are changed by different LH concentration.
authors.affiliation: Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Inada-machi, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Murayama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Akio
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000107:Acetylation; D000735:Androstenedione / Q000096:biosynthesis*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics / Q000378:metabolism; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism; D013799:Theca Cells / Q000201:enzymology* / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; D006657:Histones; D010750:Phosphoproteins; D054339:Steroidogenic Factor 1; D000098682:Steroidogenic Acute Regulatory Protein; D000735:Androstenedione; D011374:Progesterone; D007986:Luteinizing Hormone; D013254:Steroid 17-alpha-Hydroxylase