Green tea polyphenols inhibit testosterone production in rat Leydig cells

• Published in: Asian journal of andrology 2009-05, Vol.11 (3), p.362-370
• Main Authors: Figueiroa, Marina S, César Vieira, Juliany S B, Leite, Disleide S, Filho, Ruben C O Andrade, Ferreira, Fabiano, Gouveia, Patrícia S, Udrisar, Daniel P, Wanderley, Maria I
• Format: Article
• Language: English
• Subjects: Androstenedione - pharmacology; Animals; Camellia sinensis; Chorionic Gonadotropin - pharmacology; Cyclic AMP-Dependent Protein Kinases - metabolism; Flavonoids - pharmacology; Gonadotropin-Releasing Hormone - pharmacology; Humans; Leydig Cells - drug effects; Leydig Cells - metabolism; Male; Original; Phenols - pharmacology; Plant Extracts - pharmacology; Polyphenols; Protein Kinase C - metabolism; Rats; Rats, Wistar; Signal Transduction - drug effects; Testosterone - metabolism
• ISSN: 1008-682X; 1745-7262
• DOI: 10.1038/aja.2009.2

This study investigated the acute effects of green tea extract (GTE) and its polyphenol constituents, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EC), on basal and stimulated testosterone production by rat Leydig cells in vitro. Leydig cells purified in a Percoll gradient were incubated for 3 h with GTE, EGCG or EC and the testosterone precursor androstenedione, in the presence or absence of either protein kinase A (PKA) or protein kinase C (PKC) activators. The reversibility of the effect was studied by pretreating cells for 15 min with GTE or EGCG, allowing them to recover for 1 h and challenging them for 2 h with human chorionic gonadotropin (hCG), luteinizing hormone releasing hormone (LHRH), 22(R)-hydroxycholesterol or androstenedione. GTE and EGCG, but not EC, inhibited both basal and kinase-stimulated testosterone production. Under the pretreatment conditions, the inhibitory effect of the higher concentration of GTE/EGCG on hCG/LHRH-stimulated or 22(R)-hydroxycholesterol-induced testosterone production was maintained, whereas androstenedione-supported testosterone production returned to control levels. At the lower concentration of GTE/EGCG, the inhibitory effect of these polyphenols on 22(R)-hydroxycholesterol-supported testosterone production was reversed. The inhibitory effects of GTE may be explained by the action of its principal component, EGCG, and the presence of a gallate group in its structure seems important for its high efficacy in inhibiting testosterone production. The mechanisms underlying the effects of GTE and EGCG involve the inhibition of the PKA/PKC signalling pathways, as well as the inhibition of P450 side-chain cleavage enzyme and 17beta-hydroxysteroid dehydrogenase function.