PGF2alpha Inhibits 20alpha-HSD Expression by Suppressing CK1alpha-induced ERK and SP1 Activation in the Corpus Luteum of Pregnant Mice.
Qiao GaoDi ZhangJing-Lin ZhangBing-Jie WangChen-Yang LuSheng CuiPublished in: Reproductive sciences (Thousand Oaks, Calif.) (2023)
Prostaglandin F2α (PGF2α) is a luteolytic hormone that promotes parturition in mammals at the end of pregnancy by reducing progesterone secretion from the corpus luteum (CL). In rodents and primates, PGF2α rapidly converts progesterone to 20α-hydroxyprogesterone (20α-OHP) by promoting 20α-hydroxysteroid dehydrogenase (20α-HSD) expression. However, the specific mechanism of 20α-HSD regulation by PGF2α remains unclear. Casein Kinase 1α (CK1α) is a CK1 family member that regulates a variety of physiological functions, including reproductive development. Here, we investigated the effects of CK1α on pregnancy in female mice. Our experiments showed that CK1α is expressed in mouse CL, and its inhibition enhanced progesterone metabolism, decreased progesterone levels, and affected mouse embryo implantation. Further, CK1α mediated the effect of PGF2α on 20α-HSD in mouse luteal cells in vitro. Our results are the first to show that CK1α affects the 20α-HSD mRNA level by affecting the ERK signalling pathway to regulate the expression of the transcription factor SP1. These findings improve our understanding of PGF2α regulation of 20α-HSD.
Keyphrases
- protein kinase
- poor prognosis
- preterm birth
- transcription factor
- signaling pathway
- binding protein
- estrogen receptor
- induced apoptosis
- cell proliferation
- pregnant women
- pregnancy outcomes
- high fat diet induced
- type diabetes
- long non coding rna
- high resolution
- oxidative stress
- diabetic rats
- high glucose
- atomic force microscopy
- tyrosine kinase
- high speed
- single molecule