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Updated: Jun 6, 2025

A Tissue Culture Model of Estrogen-producing Primary Bovine Granulosa Cells
Published on: September 6, 2018
Acetaminophen overdose inhibits steroidogenic acute regulatory protein expression by reducing AKT-mediated SP1
Jung-Chien Cheng1, Qian Zhang1, Lingling Zhang1
1Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Abstract:
Overdose of acetaminophen (APAP) has been shown to adversely affect the outcome of pregnancy. The steroidogenic acute regulatory protein (StAR) plays a pivotal role in steroidogenesis, but the impact of APAP on StAR expression in adult human ovarian granulosa cells remains elusive. Here, we demonstrate that APAP overdose leads to the downregulation of StAR expression in the human granulosa cell tumor cell line, KGN, and in the primary culture of human granulosa-lutein (hGL) cells. Treatment of overdose APAP inhibits the activation of the AKT signaling pathway and downregulates the expression of transcription factor SP1. Using a small molecule of AKT activator and SP1 overexpression approaches, we show that the suppressive effect of APAP on StAR expression is mediated through the inhibition of AKT-mediated upregulation of SP1 expression. This study contributes to a deeper understanding of the pharmacological actions of APAP and its impacts on female reproductive health.
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