Gonadotropic regulation of circadian clockwork in rat granulosa cells

• Published in: Molecular and cellular biochemistry 2007-08, Vol.302 (1-2), p.111-118
• Main Authors: He, Pei-Jian, Hirata, Masami, Yamauchi, Nobuhiko, Hashimoto, Seiichi, Hattori, Masa-aki
• Format: Article
• Language: English
• Subjects: Animals; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Circadian clock; Circadian rhythm; Circadian Rhythm - drug effects; Circadian rhythms; Corpus Luteum - drug effects; Corpus Luteum - metabolism; CREB; Female; Follicle Stimulating Hormone - pharmacology; Gene Expression Regulation - drug effects; gonadotropins; Gonadotropins - pharmacology; Gonadotropins, Equine - pharmacology; Granulosa Cells - cytology; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Luciferases - metabolism; Luteinizing Hormone - pharmacology; Mice; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Per1; Period Circadian Proteins; Physiology; Rats; Response Elements; Rodents; Transcription Factors - genetics; Transcription Factors - metabolism; Transgenic rat
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-007-9432-7

The circadian clock is responsible for the generation of circadian rhythms in hormonal secretion and metabolism. These peripheral clocks could be reset by various cues in order to adapt to environmental variations. The ovary can be characterized as having highly dynamic physiology regulated by gonadotropins. Here, we aimed to address the status of circadian clock in the ovary, and to explore how gonadotropins could regulate clockwork in granulosa cells (GCs). To this end, we mainly utilized the immunohistochemistry, RT-PCR, and real-time monitoring of gene expression methods. PER1 protein was constantly abundant across the daily cycle in the GCs of immature ovaries. In contrast, PER1 protein level was obviously cyclic through the circadian cycle in the luteal cells of pubertal ovaries. In addition, both FSH and LH induced Per1 expression in cultured immature and mature GCs, respectively. The promoter analysis revealed that the Per1 expression was mediated by the cAMP response element binding protein. In cultured transgenic GCs, both FSH and LH also induced the circadian oscillation of Per2. However, the Per2 oscillation promoted by FSH quickly dampened within only one cycle, whereas the Per2 oscillation promoted by LH was persistently maintained. Collectively, these findings strongly suggest that both FSH and LH play an important role in regulating circadian clock in the ovary; however, they might exert differential actions on the clockwork in vivo due to each specific role within ovarian physiology.