Gonadotropic regulation of circadian clockwork in rat granulosa cells

May 8, 2007Molecular and cellular biochemistry

Hormones that control reproduction influence the daily biological clock in rat ovarian cells

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Abstract

PER1 protein was constantly abundant across the daily cycle in granulosa cells of immature ovaries.

The circadian clock in the ovary shows dynamic regulation by gonadotropins.
PER1 protein levels exhibit a cyclic pattern in luteal cells of pubertal ovaries.
FSH and LH induce Per1 expression in cultured immature and mature granulosa cells, respectively.
Per1 expression is mediated by a specific protein that responds to cAMP signals.
FSH and LH induce circadian oscillation of Per2 in cultured granulosa cells, but their effects differ over time.

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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.

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Gonadotropic regulation of circadian clockwork in rat granulosa cells

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