Acetaminophen overdose inhibits steroidogenic acute regulatory protein expression by reducing AKT-mediated SP1 expression in human granulosa-lutein cells

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.

Keywords: AKT; Acetaminophen; Granulosa cells; SP1; StAR.