INDUCED ABLATION OF GONADOTROPINS IN TRANSGENIC MICE EXPRESSING HERPES-SIMPLEX VIRUS THYMIDINE KINASE UNDER THE FSH BETA-SUBUNIT PROMOTER

Suppression of gonadotropins was induced by gancyclovir or acyclovir t reatment in transgenic mice carrying 2.3 kb of bovine follicle-stimula ting hormone beta (FSH beta) promoter fused to Herpes simplex virus th ymidine kinase (tk) coding sequence. Transgenic tk and endogenous FSH beta were immunohistochemically co-localized in the same pituitary cel ls. In adult castrated transgenic males, gancyclovir treatment reduced plasma FSH (30%, P < 0.001). In intact juvenile gancyclovir treated m ice, the reduction of pituitary FSH, and in males also of plasma FSH, was greater (50-70%, P < 0.05-0.01). A concomitant suppression of lute inizing hormone (LH) (50%, P < 0.01) was observed in female pups. The most pronounced reduction of gonadotropins was observed in newborn tra nsgenic pups treated in utero with acyclovir. Both males and females h ad significantly lower pituitary levels of FSH (75-55%), LH (80-90%) o r both (P < 0.05-0.01). Less pronounced decreases (30-40%, P < 0.01) w ere observed in plasma FSH. No apparent defects were seen in the teste s of the transgenic, acyclovir treated, newborn pups. This mouse model is applied to study the dynamics of the gonadotropes and the role of gonadotropins in the maturation of the reproductive functions.