Knowledge Gap in Understanding the Steroidogenic Acute Regulatory Protein Regulation in Steroidogenesis Following Exposure to Bisphenol A and Its Analogues

Nur Erysha Sabrina Jefferi; Asma' 'Afifah Shamhari; Zariyantey Abd Hamid; Siti Balkis Budin; Adam Muhammad Zackry Zulkifly; Fatin Norisha Roslan; Izatus Shima Taib

doi:10.3390/biomedicines10061281

Knowledge Gap in Understanding the Steroidogenic Acute Regulatory Protein Regulation in Steroidogenesis Following Exposure to Bisphenol A and Its Analogues

Biomedicines. 2022 May 30;10(6):1281. doi: 10.3390/biomedicines10061281.

Authors

Nur Erysha Sabrina Jefferi¹, Asma' 'Afifah Shamhari¹, Zariyantey Abd Hamid¹, Siti Balkis Budin¹, Adam Muhammad Zackry Zulkifly¹, Fatin Norisha Roslan¹, Izatus Shima Taib¹

Affiliation

¹ Centre of Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.

Abstract

The use of bisphenols has become extremely common in our daily lives. Due to the extensive toxic effects of Bisphenol A (BPA), the industry has replaced this endocrine-disrupting chemical (EDC) with its analogues, which have been proven to decrease testosterone levels via several mechanisms, including targeting the steroidogenic acute regulatory (StAR) protein. However, when exposed to BPA and its analogues, the specific mechanism that emerges to target StAR protein regulations remains uncertain. Hence, this review discusses the effects of BPA and its analogues in StAR protein regulation by targeting cAMP-PKA, PLC-PKC, EGFR-MAPK/ERK and Ca²⁺-Nur77. BPA and its analogues mainly lead to decreased LH in blood and increased ERK expression and Ca²⁺ influx, with no relationship with the StAR protein regulation in testicular steroidogenesis. Furthermore, the involvement of the cAMP-PKA, PLC-PKC, and Nur77 molecules in StAR regulation in Leydig cells exposed to BPA and its analogues remains questionable. In conclusion, although BPA and its analogues have been found to disrupt the StAR protein, the evidence in connecting the signaling pathways with the StAR regulations in testicular steroidogenesis is still lacking, and more research is needed to draw a solid conclusion.

Keywords: BPA analogues; Ca2+; ERK; MAPK; Nur77; PKA; cAMP; testicular steroidogenesis.

Publication types

Review

Grants and funding

This work was funded by the Fundamental Research Grant Scheme (FRGS), FRGS/1/2021/STG03/UKM/02/3, from the Ministry of Higher Education (MOHE), Malaysia. This work was also supported by the Centre for Diagnostic, Therapeutic and Investigative Studies (CODTIS), Faculty of Health Sciences, (UKM).