Vashistha, A and Khan, HR and Rudraiah, M (2021) Role of cAMP/PKA/CREB pathway and β-arrestin 1 in LH induced luteolysis in pregnant rats. In: Reproduction, 162 (1). pp. 21-31.
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Abstract
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.
| Item Type: | Journal Article |
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| Publication: | Reproduction |
| Publisher: | BioScientifica Ltd. |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | 20alpha hydroxysteroid dehydrogenase; beta arrestin 1; chorionic gonadotropin; cyclic AMP; cyclic AMP dependent protein kinase; cyclic AMP responsive element binding protein; luteinizing hormone; mitogen activated protein kinase; small interfering RNA; beta arrestin 1; CREB1 protein, rat; cyclic AMP; cyclic AMP dependent protein kinase; cyclic AMP responsive element binding protein; luteinizing hormone, animal cell; animal experiment; Article; cAMP signaling; controlled study; corpus luteum; correlation analysis; desensitization; female; in vitro study; luteal cell; luteolysis; nonhuman; pregnancy; protein analysis; protein depletion; protein expression; protein function; rat; receptor down regulation; signal transduction; animal; corpus luteum; drug effect; gene expression regulation; genetics; metabolism; Wistar rat, Animals; beta-Arrestin 1; Corpus Luteum; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Female; Gene Expression Regulation; Luteinizing Hormone; Luteolysis; Pregnancy; Rats; Rats, Wistar |
| Department/Centre: | Division of Biological Sciences > Molecular Reproduction, Development & Genetics |
| Date Deposited: | 30 Nov 2023 03:34 |
| Last Modified: | 30 Nov 2023 03:34 |
| URI: | https://eprints.iisc.ac.in/id/eprint/82975 |
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