Background: The phytoestrogen resveratrol found in grapes and other plants has attracted considerable interest due to its proposed ability to extend lifespan, attenuate the development of metabolic syndrome in obese subjects and protect against cardiovascular disease. Among other functions resveratrol has been reported to affect the endocrine system. Self-medication with high pharmacological doses of this polyphenol with the aim to improve metabolic parameters and health cannot be excluded in some health-seeking populations of humans. Prenatal involuntary foetal exposure to resveratrol due to consumption by pregnant women may negatively influence development of endocrine homeostasis and stress responsiveness in human foetuses.
Objective and hypotheses: The aim of this project was to explore the potential of resveratrol to affect human foetal adrenal steroidogenesis and mitochondrial function at the end of the first trimester.
Method: Cells were isolated from gestational week 912 human foetal adrenals and cultured in vitro for 24 h with resveratrol, with or without stimulation with ACTH. DHEA, androstenedione, progesterone, 17OH-progesterone, cortisol and testosterone were analysed by ELISA. Expression of steroidogenic enzymes was measured by qPCR and Western Blotting. Cell proliferation and mitochondrial function were also analysed.
Results: Resveratrol significantly suppressed the production of DHEA and androstenedione but elevated the release of progesterone and 17OH-progesterone by primary cultures of ACTH stimulated human foetal adrenocortical cells. These alterations of steroidogenesis were associated with down-regulation of CYP17A1 expression. No significant effects of resveratrol on cell proliferation and mitochondrial function were found.
Conclusion: Resveratrol has potential to disrupt steroidogenesis in human foetal adrenals at the end of the first trimester. Since this is a critical period for the development of many steroid-dependent organs, our data constitute a warning for self-medication with resveratrol especially during pregnancy.
Funding: This work was supported by the Swedish Research Council; the Finnish Academy; the Childrens Cancer Fund; Frimurare Barnhuset Foundation; Kronprinsessan Lovisas Foundation; the Sällskapet Barnavård; the Stiftelsen Samariten; the Stiftelsen Olle Engkvist Byggmästare and the Stiftelsen Gunvor och Josef Anérs.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology