Protein tyrosine kinase activity of lavendustin A and the phytoestrogen genistein on progesterone synthesis in cultured rat ovarian cells

Objective: To compare the effects of two protein tyrosine kinase inhibitors, lavendustin A and the phytoestrogen genistein, on progesterone synthesis in cultured rat ovarian cells. Design: Experimental animal study. Setting: Medical school laboratory. Animal(s): Porton Wistar rats. Intervention(s): Ovaries from estrous rats were used to establish cell cultures of granulosa-luteal cells from freshly ruptured follicles, granulosa-luteal cells cocultured with peritoneal macrophages, and whole ovarian dispersates. Main Outcome Measure(s): Progesterone and nitrite concentrations in the culture medium. Result(s): The protein tyrosine kinase inhibitors suppressed steroid synthesis in a dose-dependent manner and completely inhibited the steroidogenic response to both FSH and the adenyl cyclase stimulator forskolin. The inhibitory action of cocultured macrophages on basal and forskolin-stimulated progesterone production in granulosa-luteal cells was not reversed by genistein, nor was the inhibitory effect of interleukin-1 beta in cultures of ovarian dispersates. Conclusion(s): Genistein and the nonestrogenic protein tyrosine kinase inhibitor lavendustin A exert potent inhibitory effects on steroidogenesis that are independent of cytokines. The toxic effects of genistein on sexual development and reproduction may be attributed not only to its estrogenic action but also to its action as a protein tyrosine kinase inhibitor. (C) 2000 by American Society for Reproductive Medicine.