Abstract
Crude aqueous extracts of the plant Lithospermum ruderale have been shown to have antigonadotropic activity that resides in its polyphenolic fractions. This study examined the ability of one such polyphenol, lithospermic acid (LA), and its oxidation product(s) (oxyLA) to inhibit luteinizing hormone (LH) secretion in vitro. Primary pituitary cultures were exposed for 4.5 or 6 h to either LA or oxyLA. In the presence of gonadotropin-releasing hormone (GnRH), oxyLA was at least 10 times more potent than LH in inhibiting LH release. In the absence of GnRH, oxyLA but not LA caused an increase in LH release. After washing to remove the oxyLA and LA, cultures were challenged with GnRH. Only cultures pretreated with oxyLA showed a decrease in GnRH-stimulated LH release. These results indicate that oxyLA may contain the primary antigonadotropic agents in L. ruderale. The different responses observed in the presence and absence of GnRH, and the morphologic features of the oxyLA-treated cultures, suggest that the mechanism of action may involve the cell membrane of the gonadotrope.
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