Role of cAMP/PKA/CREB pathway and β-arrestin 1 in LH induced luteolysis in pregnant rats
| Autor: | Medhamurthy Rudraiah, H Rahaman Khan, Akshi Vashistha |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Embryology medicine.medical_specialty Luteolysis Luteal phase Biology CREB 03 medical and health sciences 0302 clinical medicine Endocrinology Desensitization (telecommunications) Corpus Luteum Pregnancy Internal medicine medicine Cyclic AMP Animals Rats Wistar Cyclic AMP Response Element-Binding Protein 030219 obstetrics & reproductive medicine Kinase Obstetrics and Gynecology Cell Biology Luteinizing Hormone Cyclic AMP-Dependent Protein Kinases Rats 030104 developmental biology medicine.anatomical_structure beta-Arrestin 1 Reproductive Medicine Gene Expression Regulation biology.protein Female Signal transduction Luteinizing hormone Corpus luteum |
| Zdroj: | Reproduction (Cambridge, England). 162(1) |
| ISSN: | 1741-7899 |
| Popis: | Luteal dysfunction in pregnant women is associated with early pregnancy loss, making the study of structure and function of the corpus luteum (CL) critical. Luteinizing hormone (LH) plays a crucial role in the mammalian female reproduction majorly by regulating luteal development. In rats, the luteotropic roles of LH have been widely investigated but its role in the process of luteolysis has received little attention. In this study, we explored the luteolytic actions of LH during different stages of pregnancy in rats. Repeated administration of LH during the late and mid-stages of pregnancy led to functional luteolysis during both stages, while structural luteolysis was observed only during the late-stage. We analyzed the involvement of cAMP/PKA/CREB pathway, MAP kinases and β-arrestins to elucidate the molecular mechanism of LH-mediated luteolysis. The results indicate that the repeated administration of LH causes LH/CGR desensitization along with an increase in β-arrestin 1 expression, while luteal expression of MAP kinases remained unaffected. Further, siRNA-mediated depletion of β-arrestin 1 in primary luteal-cell cultures prevents initiation of the luteolysis process to some extent during both the stages of pregnancy, underscoring its role in LH mediated-luteolysis. In conclusion, the luteolytic actions of LH appear to involve more than one signaling pathway and cAMP/PKA/CREB pathway appears to be the key regulator. This is the first report to show a positive correlation between β-arrestin 1 and 20α-hsd expression. These findings have implications for our understanding of the molecular pathways that regulate luteolysis. |
| Databáze: | OpenAIRE |
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