Abstract
The highly conserved polo-like kinases (Plks) are potent regulators of multiple functions in the cell cycle before and during mitotic cell division. We investigated the expression pattern of Plk genes and their potential role(s) in the rat ovary during the periovulatory period. Plk2 and Plk3 were highly induced both in intact ovaries and granulosa cells in vivo after treatment with the luteinizing hormone (LH) agonist, human chorionic gonadotropin (hCG). In vitro, hCG stimulated the expression of Plk2 in granulosa cells, but not Plk3. This induction of Plk2 expression was mimicked by both forskolin and phorbol 12 myristate 13-acetate (PMA). Moreover, Plk2 expression was reduced by inhibitors of prostaglandin synthesis or the EGF pathway, but not by progesterone receptor antagonist (RU486) treatment. At the promoter level, mutation of the Sp1 binding sequence abolished the transcriptional activity of the Plk2 gene. ChIP assays also revealed the interaction of endogenous Sp1 protein in the Plk2 promoter region. Functionally, the over-expression of Plk2 and Plk3 arrested granulosa cells at the G0/G1 phase of the cell cycle. In contrast, the knockdown of Plk2 expression in granulosa cells decreased the number of cells in the G0/G1 stage of the cell cycle, but increased granulosa cell viability. In summary, hCG induced Plk2 and Plk3 expression in the rat ovary. Prostaglandins and the EGF signaling pathway are involved in regulating Plk2 expression. The transcription factor Sp1 is important for Plk2 transcriptional up-regulation. Our findings suggest that the increase in Plk2 and Plk3 expression contributes to the cell cycle arrest of granulosa cells which is important for the luteinization of granulosa cells during the periovulatory period.
Highlights
In females, an acute rise of luteinizing hormone (LH) released from the pituitary triggers ovulation and induces terminal differentiation of preovulatory granulosa cells to become luteal cells
The results showed that human chorionic gonadotropin (hCG) induced a similar pattern of Plk2 mRNA expression in cultured granulosa cells (Fig. 3A) comparable to its expression in vivo (Fig. 2A), with the exception that the highest expression was observed at 4 h after hCG in vitro
In response to the LH surge, proliferating granulosa cells undergo an irreversible exit from the cell cycle and differentiate to luteal cells
Summary
An acute rise of luteinizing hormone (LH) released from the pituitary (called the LH surge) triggers ovulation and induces terminal differentiation of preovulatory granulosa cells to become luteal cells. The LH surge terminates granulosa cell proliferation and initiates a program of luteinization in which the cells stop their division and differentiate into luteal cells [1]. The cell cycle progression of periovulatory granulosa cells is controlled by a delicate balance between positive and negative regulators. Members of the family of polo-like kinases (Plks) were reported to be major cell cycle regulators in differentiated cells [2]. Plk was first reported to associate with mitotic spindle poles in the Drosophila melanogaster polo mutation [3]. Five mammalian Plks family members have been characterized in murine and human, including Plk (Xenopus Plx1), Plk2/Snk (Xenopus Plx2), Plk3/Prk/FnK (Xenopus Plx3), Plk4/Sak and Plk5 [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
