title: Factors regulating the bovine, caprine, rat and human ovarian aromatase promoters in a bovine granulosa cell model.
abstract: The ovarian promoter of the primate and rodent genes encoding cytochrome P450 aromatase (CYP19A1) are robustly responsive to forskolin in luteinized cell models, whereas the ruminant ovarian promoter is minimally active. We explored this discrepancy by investigating the activity of the bovine ovarian promoter in two bovine granulosa cell models, luteinizing and non-luteinizing cells in vitro. In non-luteinizing cells, both FSH and IGF1 increased abundance of transcripts derived from the ovarian promoter. Comparison of the activity of promoters of several species in response to transcription factors (forskolin, NR5A2, FOXL2) in luteinizing cells demonstrated that a rat ovarian promoter-luciferase reporter was regulated mainly by forskolin (18-fold increase over basal expression) and addition of NR5A2 or FOXL2 had no further effect. Activity of a human promoter was significantly increased by NR5A2 plus forskolin (153-fold) compared with forskolin alone (71-fold over basal); addition of FOXL2 did not significantly increase promoter activity. Forskolin alone provoked minor activation of caprine and bovine promoter reporters (3-fold over basal), and addition of NR5A2 increased activity (7- to 11-fold). When forskolin, NR5A2 and FOXL2 treatments were combined, the activity of the caprine and bovine promoters increased to 20- and 34-fold, respectively. These data suggest that a major reason why CYP19A1 is not expressed in luteinized cells (and the corpus luteum) of ruminants may be the stimulatory effect of FOXL2, which does not appear to be the case in the human and rat.
authors.affiliation: Centre de recherche en reproduction animale, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC, Canada.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Sahmi
authors.affiliation: Centre de recherche en reproduction animale, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC, Canada.
authors.forename: Edmir S
authors.initials: ES
authors.lastname: Nicola
authors.affiliation: Centre de recherche en reproduction animale, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC, Canada.
authors.forename: Gustavo O
authors.initials: GO
authors.lastname: Zamberlam
authors.affiliation: Centre de recherche en reproduction animale, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC, Canada.
authors.forename: Paulo D B
authors.initials: PD
authors.lastname: Gonçalves
authors.affiliation: Reproductive Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Vanselow
authors.affiliation: Centre de recherche en reproduction animale, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC, Canada. Electronic address: christopher.price@umontreal.ca.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Price
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D003338:Corpus Luteum / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006041:Goats; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D034461:Luteinization / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism; D013045:Species Specificity; D014162:Transfection
chemical_list: D051858:Forkhead Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear; D011962:Receptors, FSH; D005576:Colforsin; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Aromatase; FOXL2; Granulosa; NR5A2; Ruminant