Effects of Azoles on the In vitro Follicular Steroidogenesis in Amphibians

다국어 초록 (Multilingual Abstract)

Azoles are widely used antifungal agents, whichinhibit the biosynthesis of fungal cell-membrane ergosterol.In this study, using an amphibian follicle culture system, theeffects of azoles on follicular steroidogenesis in frogs wereexamined. Itraconazole (ICZ), clotrimazole (CTZ) andketoconazole (KCZ) suppressed pregnenolone (P5) productionby the follicles (ED50; 0.04M, 0.33M, and 0.91M,(FPH). However, fluconazole (FCZ), miconazole (MCZ) andeconazole (ECZ) were not effective in the suppression of P5production. Not all the azoles examined suppressed theconversion of exogenous P 5 to progesterone (P4) (by 3β-HSD) or P4 to 17α-hydroxyprogesterone (17α-OHP) (by17α-hydroxylase), or androstenedione (AD) to testosterone(T) (by 17β-HSD). In contrast, CTZ, MCZ and ECZ inα-OHP toAD (by C17-20 lyase) (ED50; 0.25M, 4.5M, and 0.7M,respectively) and CTZ, KCZ, ECZ and MCZ stronglysuppressed the conversion of exogenous T to estradiol (E2)(by aromatase) (ED50; 0.02 M, 8M, 0.07M, 0.8M,respectively). These results demonstrated that some azoleand particularly, P450scc and aromatase are more sensitiveto azoles than other steroidogenic enzymes.

참고문헌 (Reference)

1 Aoyama Y, "Sterol 14-demethylase P450 (P45014DM) is one of the most ancient and conserved P450 species" 119 : 926-933, 1996

2 Walsh LP, "Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression" 2000a

3 Ahn RS, "Roles of Theca and Granulosa cels in Follicular Steroidogenesis in Rana dybowski." 39 : 273-281, 1996

4 Muray R, "Role of anti-aromatase agents in postmenopausal advanced breast cancer." 48 : 259-265, 2001

5 Kwon HB, "Relative roles of theca andINTEGRATIVEBIOSCIENCES Vol. 10 No. 4 209Azoles on follicular steroidogenesisgranulosa cells in ovarian follicular steroidogenesis in theamphibian" 207-214, 1994

6 Pedro RRM, "Polycyclic aromatic hydrocarbons inhibit in vitro ovarian steroidogenesis in theflounder." 48 : 549-559, 2000

7 Payne AH, "Overview of steroidogenic enzymes in the pathway from cholesterol to active steroidhormones." 25 : 947-970, 2004

8 Joseph-Horne T, "Molecular mechanisms of azole resistance in fungi." 149 : 141-149, 1997

9 Conley A, "Mammalian aromatases." 121 : 685-695, 2001

10 Ahn RS, "Evidence for two-cell model of steroidogenesis in four species of amphibian." 284 : 91-99, 1999

11 Tsafriri A, "Efects ofketoconazole on ovulatory changes in the rat implications onthe role of a meiosis-activating sterol." 4 : 483-489, 1998

12 Kwon HB, "Dichotomous effects offorskolin on somatic and germ cell components of the ovarianfolicle evidence of cAMP involvement in steroid productionand action. J Exp Zool 236" 219-228, 1985

13 Espinel-Ingroff A, "Clinical relevance of antifungal resistance." 1 : 929-944, 1997

14 Petrino T, "Cholesterol mediation ofprogesterone production and oocyte maturation in culturedamphibian" 36 1219-1228, 1987

15 Kwon HB, "Changes in the activities of steroidogenic enzymesduring the development of ovarian folicles in Rananigromaculata. Gen Comp Endocrinol 92" 225-232, 1993

16 Georgopapadakou NH, "Antifungals: mechanism of action and resistance, established and novel drugs" 1 : 547-557, 1998