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Published on: October 2, 2018
Cyclin-dependent kinase 5 regulates steroidogenic acute regulatory protein and androgen production in mouse Leydig
Ho Lin1, Mei-Chih Chen, Chien-Te Ku
1Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan. hlin@dragon.nchu.edu.tw
Abstract:
The roles of cyclin-dependent kinase 5 (Cdk5) in central nervous system and neurodegenerative diseases have been intensely investigated in recent decades. Because protein expressions of Cdk5 and its regulator, p35, have been identified in Leydig cells, it is informative to further explore the novel function of Cdk5/p35 in male reproduction. Here we show that Cdk5/p35 protein expression and kinase activity in mouse Leydig cells are regulated by human chorionic gonadotrophin (hCG) in both dose- and time-dependent manners. Blocking of Cdk5 by molecular inhibitors or small interfering RNA resulted in reduction of testosterone production by Leydig cells. cAMP, a second messenger in LH signaling, was identified as a factor in hCG-dependent regulation of Cdk5/p35. Importantly, Cdk5 protein and kinase activity could support accumulation of steroidogenic acute regulatory (StAR) protein, a crucial component of steroidogenesis. We additionally addressed the protein interaction between Cdk5/p35 and StAR. The Cdk5-dependent serine phosphorylation of StAR indicated a possible mechanism by which Cdk5 induced accumulation of StAR protein. In conclusion, Cdk5 modulates hCG-induced androgen production in mouse Leydig cells, possibly through regulation of StAR protein levels. These results indicate that Cdk5 may play an important role in male reproductive endocrinology and is a potential therapeutic target in androgen-related diseases.
Insights
Cyclin-dependent kinase 5 (Cdk5) regulates testosterone production in mouse Leydig cells. Cdk5/p35 activity, influenced by hCG, impacts steroidogenic acute regulatory (StAR) protein, crucial for male reproduction.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Biology
Background:
- Cyclin-dependent kinase 5 (Cdk5) is known for its roles in the central nervous system.
- Cdk5 and its regulator p35 are expressed in Leydig cells, suggesting a role in male reproduction.
Purpose of the Study:
- To investigate the function of Cdk5/p35 in male reproduction.
- To explore the regulation and effects of Cdk5/p35 in mouse Leydig cells.
Main Methods:
- Investigated Cdk5/p35 expression and activity in mouse Leydig cells.
- Utilized molecular inhibitors and small interfering RNA to block Cdk5.
- Analyzed the role of cAMP in hCG-dependent regulation.
- Examined the interaction between Cdk5/p35 and steroidogenic acute regulatory (StAR) protein.
Main Results:
- Human chorionic gonadotrophin (hCG) regulates Cdk5/p35 expression and kinase activity in a dose- and time-dependent manner.
- Cdk5 inhibition reduced testosterone production.
- cAMP is involved in hCG-mediated Cdk5/p35 regulation.
- Cdk5 activity promotes StAR protein accumulation through serine phosphorylation.
Conclusions:
- Cdk5 modulates hCG-induced androgen production in mouse Leydig cells, likely via StAR protein regulation.
- Cdk5 is important in male reproductive endocrinology and a potential therapeutic target for androgen-related diseases.
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