1. Interaction of ovarian steroidogenesis and clock gene expression modulated by bone morphogenetic protein-7 in human granulosa cells
- Author
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Nahoko Iwata, Takaaki Takiguchi, Tamami Aokage, Satoko Nagao, Fumio Otsuka, Toru Hasegawa, Takahiro Nada, Yoshiaki Soejima, Yuka Kozato, and Yasuhiro Nakano
- Subjects
endocrine system ,3-Hydroxysteroid Dehydrogenases ,Bone Morphogenetic Protein 7 ,Endocrinology, Diabetes and Metabolism ,CLOCK Proteins ,Gene Expression ,030209 endocrinology & metabolism ,Positive correlation ,03 medical and health sciences ,chemistry.chemical_compound ,Aromatase ,0302 clinical medicine ,Endocrinology ,Downregulation and upregulation ,Cell Line, Tumor ,Humans ,Progesterone ,Gene knockdown ,Messenger RNA ,Granulosa Cells ,Forskolin ,Estradiol ,Colforsin ,Cell biology ,PER2 ,Bone morphogenetic protein 7 ,CLOCK ,chemistry ,030220 oncology & carcinogenesis ,Female - Abstract
A functional link between clock gene expression and ovarian steroidogenesis was studied using human granulosa KGN cells. Similarities between changes in the mRNA and protein expression levels of Bmal1 and Clock and those of Per2 and Cry1 were found in KGN cells after treatment with forskolin. Among the interrelationships between the expression levels of clock and steroidogenic factors, Clock mRNA had a strongly positive correlation with P450arom and a negative correlation with 3βHSD. Knockdown of Clock gene by siRNA resulted in a significant reduction of estradiol production by inhibiting P450arom expression, while it induced a significant increase of progesterone production by upregulating 3βHSD in KGN cells treated with forskolin. Moreover, BMP-7 had an enhancing effect on the expression of Clock mRNA and protein in KGN cells. Thus, the expression levels of Clock, being upregulated by forskolin and BMP-7, were functionally linked to estradiol production and progesterone suppression by human granulosa cells.
- Published
- 2019