Effects of fungal metabolites on testosterone secretion in vitro

To study the direct effect of mycotoxins belonging to different chemical classes on testicular function, dispersed interstitial cells from testes of adult gerbils were short-term cultured either in the absence or presence of mycotoxins, and testosterone secretion was measured. When interstitial cells were incubated with T-2 toxin (0.0076-38.3 nM) there was a dose-dependent decrease of testosterone production (r = -0.72, ID50 = 0.042 nM). Since neither progesteronenor DHEA-stimulated testosterone production was affected by T-2 toxin, the observed inhibition of basal secretion was apparently due to a decrease of pregnenolone production and/or conversion of pregnenolone to progesterone. Much higher concentrations of zearalenone or of ochratoxin A were necessary to induce a similar inhibition of steroidogenesis (369 microM and 1838 microM, respectively) when compared to T-2 toxin. In contrast, citrinin or cyclopiazonic acid affected testosterone secretion only slightly, values reaching significant levels at doses of 1.74 nM (citrinin) and 149 nM (cyclopiazonic acid). In the presence of kojic acid (2.63-2633 nM) a significant, though not dose-dependent inhibition of testosterone secretion was observed. From these experiments it is concluded that mycotoxins of distinct chemical structure act directly on testicular tissue, presumably by inhibiting early steps of the steroidogenic pathway.