Circadian clock gene regulation of steroidogenic acute regulatory protein gene expression in preovulatory ovarian follicles.
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.
Nakao
Nobuhiro
N
Division of Biomodeling, Graduate School of Bioagricultural Sciences and Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Yasuo
Shinobu
S
Nishimura
Atsuko
A
Yamamura
Takashi
T
Watanabe
Tsuyoshi
T
Anraku
Tsubasa
T
Okano
Toshiyuki
T
Fukada
Yoshitaka
Y
Sharp
Peter J
PJ
Ebihara
Shizufumi
S
Yoshimura
Takashi
T
D056930:ARNTL Transcription Factors; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D056926:CLOCK Proteins; D002478:Cells, Cultured; D002940:Circadian Rhythm; D003370:Coturnix / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D010060:Ovulation / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D000098682:Steroidogenic Acute Regulatory Protein
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D000098682:Steroidogenic Acute Regulatory Protein; C538960:BMAL1 protein, human; C538943:CLOCK protein, human