Human forkhead L2 represses key genes in granulosa cell differentiation including aromatase, P450scc, and cyclin D2.
FOXL2 is expressed in granulosa cells (GC) of small and medium ovarian follicles, functions as a repressor of the human steroidogenic acute regulatory gene, a marker of a GC differentiation, and its mutation is associated with premature ovarian failure (POF) in women with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), type I. We now report that FOXL2 also represses the transcription of aromatase, P450scc, and cyclin D2, three other key genes involved in GC proliferation, differentiation, and steroidogenesis, and that a FOXL2 mutation found in patients with BPES type I, also fails to repress aromatase transcription, further supporting a role for FOXL2 in follicle maturation.
Bentsi-Barnes
Ikuko K
IK
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics/Gynecology, Cedars-Sinai Medical Center, Los Angeles, California 90048 , USA.
Kuo
Fang-Ting
FT
Barlow
Gillian M
GM
Pisarska
Margareta D
MD
D000818:Animals; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D056742:Cyclin D2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006107:Granulosa Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D012097:Repressor Proteins / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics
C080336:CCND2 protein, human; D056742:Cyclin D2; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins; D001141:Aromatase; D002786:Cholesterol Side-Chain Cleavage Enzyme