Circadian clock gene regulation of steroidogenic acute regulatory protein gene expression in preovulatory ovarian follicles

Nobuhiro Nakao, Shinobu Yasuo, Atsuko Nishimura, Takashi Yamamura, Tsuyoshi Watanabe, Tsubasa Anraku, Toshiyuki Okano, Yoshitaka Fukada, Peter J. Sharp, Shizufumi Ebihara, Takashi Yoshimura*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)


It is now known that circadian clocks are localized not only in the central pacemaker but also in peripheral organs. An example of a clock-dependent peripheral organ is the ovary of domestic poultry in which ovulation is induced by the positive feedback action of ovarian progesterone on the neuroendocrine system to generate a preovulatory release of LH during a daily 6-10 h "open period" of the ovulatory cycle. It has been assumed previously that the timing of ovulation in poultry is controlled solely by a clock-dependent mechanism within the neuroendocrine system. Here, we question this assumption by demonstrating the expression of the clock genes, Per2 (Period 2) and Per3, Clock, and Bmal1 (brain and muscle Arnt-like protein 1), in preovulatory follicles in laying quail. Diurnal changes in Per2 and Per3 expression were seen in the largest preovulatory follicle (F1) but not in smaller follicles. We next sought to identify clock-driven genes in preovulatory follicles focusing on those involved in the synthesis of progesterone. One such gene was identified, encoding steroidogenic acute regulatory protein (StAR), which showed 24-h changes in expression in the F1 follicle coinciding with those of Per2. Evidence that StAR gene expression is clock driven was obtained by showing that its 5′ flanking region contains E-box enhancers that bind to CLOCK/BMAL1 heterodimers to activate gene transcription. We also showed that LH administration increased the promoter activity of chicken StAR. We therefore suggest that the timing of ovulation in poultry involves an LH-responsive F1 follicular clock that is involved in the timing of the preovulatory release of progesterone.

Original languageEnglish
Pages (from-to)3031-3038
Number of pages8
Issue number7
Publication statusPublished - 2007 Jul
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology


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