PITUITARY AND OVARIAN EXPRESSION OF THE ENDOGENOUS FOLLICLE-STIMULATING-HORMONE (FSH) SUBUNIT GENES AND AN FSH BETA-SUBUNIT PROMOTER-DRIVENHERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE IN TRANSGENIC MICE - SPECIFIC PARTIAL ABLATION OF FSH-PRODUCING CELLS BY ANTIHERPES TREATMENT

The ovarian expression of the endogenous follicle-stimulating hormone beta-subunit (FSH beta) and common alpha-subunit (C alpha) genes, and a herpes simplex virus thymidine kinase (tk) transgene, driven by a 2. 3 kb bovine FSH beta promoter, was studied in normal and transgenic (t g) mice. tk functions not only as a neutral reporter that enables the study of the promoter function but also as an exogenously inducible to xigene, Reverse transcription-PCR followed by Southern blot hybridizat ion with a nested probe was used to show the expression of the gene at the mRNA level. Common alpha-subunit mRNA was detected in the pituita ry gland and ovaries of normal adult mice. We have previously detected endogenous FSH beta and tg tk mRNAs in the mouse pituitary, testis an d ovary. In this study, the cellular localization of the corresponding proteins was visualized by immunocytochemistry, In normal mouse ovari es a positive reaction with FSH beta and C alpha antisera was seen in some of the corpora lutea and most prominently in the interstitial cel ls. A positive reaction with the tk antiserum was seen in the same cel l types of tg mouse ovaries, but not in those of non-tg mice. Cell-abl ation-inducing treatment (gancyclovir, 20 mg/kg per day, for 14 days) of tg female mice reduced pituitary FSH concentrations by 52% (P < 0.0 5) but did not affect pituitary LH or plasma gonadotropins compared wi th non-tg females treated in the same way. A longer period of cell abl ation induction (acyclovir 400 mg/kg per day, for 21 days) reduced not only pituitary but also plasma FSH concentrations (55 and 57% respect ively; P < 0.05) without affecting LH. This treatment also reduced ova rian weight by 38% (P < 0.01). In conclusion, our results show first t hat the endogenous FSH beta and C alpha proteins are produced in the m ouse ovary. Hence, endogenously synthesized FSH or its subunits may ha ve a role in the paracrine regulation of ovarian function. Secondly, t he FSH beta promoter directs the expression of tg tk in the pituitary gonadotrope cells, as shown by specific but partial ablation of FSH-pr oducing cells after induction by gancyclovir and acyclovir. In the ova ry, tk protein was localized to the same compartments as the endogenou s gonadotropin subunit proteins. This further confirms our finding of ovarian expression of the FSH subunit genes.