Grape Polyphenols, Resveratrol, Piceatannol, Luteolin, and Myricetin: A Review of Their Influence on Ovarian, Testicular, and Adrenal Functions With a Focus on Steroidogenesis

The study of natural grape polyphenols with pharmacological activities is an emerging trend in nutritional and pharmacologic research because some have shown to have potentially beneficial health properties. The aim of this review was to summarize the published effects of four grape polyphenols, resveratrol, piceatannol, luteolin, and myricetin on ovarian, testicular (Leydig cells, LC), and adrenal gland function with a focus on their effects on steroidogenesis and cell proliferation. Studies show that low doses of resveratrol stimulate granulosa cell (GC) proliferation while higher doses inhibit their proliferation. GC progesterone secretion is increased by resveratrol but inhibited by myricetin and piceatannol, whereas estradiol secretion is stimulated by myricetin and inhibited by resveratrol, piceatannol, and luteolin. Moreover, resveratrol, myricetin and piceatannol may be beneficial in reducing environmental and drug-induced injury to GC. Studies with thecal cells (TC) indicate that resveratrol, myricetin and piceatannol all inhibit TC proliferation and steroidogenesis (androstenedione and progesterone); no study has evaluated luteolin effects on TC. Resveratrol is also inhibitory to LC steroidogenesis but luteolin is stimulatory to LC progesterone secretion. One study reported no effect of myricetin on LC viability or function, but more studies are needed. Resveratrol and piceatannol stimulate adrenal cortical cell aldosterone and progesterone secretion but inhibit cortisol and testosterone secretion. Studies with adrenal (medulla) cells indicate that resveratrol and piceatannol may attenuate excessive catecholamine secretion during stress. Future studies should evaluate myricetin and luteolin effects on adrenal function and focus on dose-responses and potential combined effects of these polyphenols on steroidogenic tissue function.