Dermatophyte-hormone relationships: characterization of progesterone-binding specificity and growth inhibition in the genera Trichophyton and Microsporum.
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 Arthroderma benhamiae and in Microsporum canis revealed a single class of binding sites with approximately the same affinity as that in T. mentagrophytes (Kd, 1 X 10(-7) to 2 X 10(-7) M). Trichophyton rubrum had a protein with a higher binding affinity (Kd, 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 degrees 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,.
Clemons
K V
KV
Department of Medicine, Stanford University School of Medicine, California 94305.
Schär
G
G
Stover
E P
EP
Feldman
D
D
Stevens
D A
DA
D001667:Binding, Competitive; D003900:Desoxycorticosterone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D008864:Microsporum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D011397:Promegestone / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014249:Trichophyton / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D003900:Desoxycorticosterone; D011374:Progesterone; D011397:Promegestone