Dermatophyte-hormone relationships: Characterization of progesterone-binding specificity and growth inhibition in the genera Trichophyton and Microsporum

Abstract

We reported previously that Trichophyton mentagrophytes contains a cytoplasmic macromolecule which specifically binds progesterone. Progesterone is also an effective inhibitor of growth of the fungus. We report here studies which characterize more fully the specific binding properties and the functional responses of T. mentagrophytes and taxonomically related fungi to a series of mammalian steroid hormones. Scatchard analysis of [3H]progesterone binding in both the + and - mating types of Athroderma benhamiae and in Microsporum canis revealed a single class of binding sites with approximately the same affinity as that in T. mentagrophytes (K(d), 1 x 10-7 to 2 x 10-7 M), Trichophyton rubrum had a protein with a higher binding affinity (K(d), 1.6 x 10-8 M). Characterization of the [3H]progesterone-binding sites in T. mentagrophytes showed the binder to be a protein which was destroyed by trypsin and heating to 56°C. Previous examination of the steroid-binding specificity in T. mentagrophytes had demonstrated that deoxycorticosterone (DOC) and dihydrotestosterone (DHT) were effective competitors for [3H]progesterone binding. Expansion of this study to include other competitors revealed that R5020 (a synthetic progestin), androstenedione, and dehydroepiandosterone possessed relative binding affinities which were 20, 11, and 9% of that of progesterone, respectively. Other ligands tested were less effective. Competition studies for the binder in M. canis resulted in similar findings: DOC and DHT were effective competitors for [3H]progesterone binding. The growth of A. benhamiae + and -, M. canis, and T. rubrum were all inhibited by progesterone in a dose-responsive manner, with 50% inhibition achieved at concentrations of 9.8 x 10-6, 1.2 x 10-5, 1.5 x 10-5, and 2.7 x 10-6 M, respectively. In addition, in the same rank order as specific progesterone binding, DOC and DHT were less effective inhibitors of growth of M. canis and T. rubrum. In conclusion, these results indicate that specific binding of progesterone appears to be a general phenomenon in dermatophytic fungi. Moreover, other steroid hormones and analogs inhibit growth in approximately the same rank order in which they displace [3H]progesterone from the fungal binders. These results further substantiate our hypothesis that the binder acts as the molecular mediator of the inhibitory effects exerted by steroid hormones on the growth of these fungi. The significance of these responses to an aspect of the biology or pathogenesis (or both) of these organisms remains to be elucidated.