Prenatal exposure to testosterone induces cardiac hypertrophy in adult female rats through enhanced Pkcδ expression in cardiac myocytes

• Published in: Journal of molecular and cellular cardiology Vol. 128; pp. 1 - 10
• Main Authors: Hou, Min, Gu, Hang-Chao, Wang, Hui-Hui, Liu, Xin-Mei, Zhou, Cheng-Liang, Yang, Qian, Jiang, Zi-Ru, Lin, Jing, Wu, Yi-Mei, Wu, Yan-Ting, Sheng, Jian-Zhong, Huang, He-Feng
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2019
• Subjects: Androgen receptor; Cardiac hypertrophy; Dihydrotestosterone; PKCδ; Cardiac hypertrophy; PKCδ; Dihydrotestosterone; Androgen receptor
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2019.01.008

High circulating androgen in women with polycystic ovary syndrome (PCOS) may increase the risk of cardiovascular disease in offspring. The aim of the present study is to investigate whether maternal androgen excess in the rat PCOS model would lead to cardiac hypertrophy in offspring. Maternal testosterone propionate (maternal-TP)–treated adult female offspring displayed cardiac hypertrophy associated with local high cardiac dihydrotestosterone (DHT). The molecular markers of cardiac hypertrophy along with androgen receptor (AR) and PKCδ, were increased in the Maternal-TP group. Treatment of primary neonatal rat ventricular cardiomyocytes (NRCMs) and H9c2 cells with DHT significantly increased cell size and upregulated PKCδ expression, which could be attenuated by AR antagonist. Treatment with phorbol 12-myristate 13-acetate (PMA), a PKC activator, significantly increased cell size and upregulated myh7 level. Rottlerin, that may inhibit PKCδ, significantly reduced the hypertrophic effect of DHT and PMA on NRCMs and H9c2 cells. Chromatin immunoprecipitation revealed that AR could bind to Pkcδ promoter. Our results indicate that prenatal exposure to testosterone may induce cardiac hypertrophy in adult female rats through enhanced Pkcδ expression in cardiac myocytes. •Maternal-TP–treated adult female offspring displayed cardiac hypertrophy associated with local high cardiac DHT level.•Androgen regulates PKCδ transcription in cardiomyocytes hypertrophy.•PKCδ may regulate cardiomyocyte growth in vitro.