Pituitary and ovarian expression of the endogenous follicle-stimulating hormone (FSH) subunit genes and an FSH β-subunit promoter-driven herpes simplex virus thymidine kinase gene in transgenic mice; specific partial ablation of FSH-producing cells by antiherpes treatment

Abstract

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 (tg) mice, tk functions not only as a neutral reporter that enables the study of the promoter function but also as an exogenously inducible toxigene. Reverse transcription-PCR followed by Southern blot hybridization 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 pituitary gland and ovaries of normal adult mice. We have previously detected endogenous FSH beta and tg tk mRNAs in the mouse pituitary, testis and ovary. In this study, the cellular localization of the corresponding proteins was visualized by immunocytochemistry. In normal mouse ovaries a positive reaction with FSH beta and C alpha antisera was seen in some of the corpora lutea and most prominently in the interstitial cells. A positive reaction with the tk antiserum was seen in the same cell types of tg mouse ovaries, but not in those of non-tg mice. Cell-ablation-inducing treatment (gancyclovir, 20 mg/kg per day, for 14 days) of tg female mice reduced pituitary FSH concentrations by 52% (P < 0.05) but did not affect pituitary LH or plasma gonadotropins compared with non-tg females treated in the same way. A longer period of cell ablation induction (acyclovir 400 mg/kg per day, for 21 days) reduced not only pituitary but also plasma FSH concentrations (55 and 57% respectively; P < 0.05) without affecting LH. This treatment also reduced ovarian weight by 38% (P < 0.01). In conclusion, our results show first that the endogenous FSH beta and C alpha proteins are produced in the mouse ovary. Hence, endogenously synthesized FSH or its subunits may have a role in the paracrine regulation of ovarian function. Secondly, the FSH beta promoter directs the expression of tg tk in the pituitary gonadotrope cells, as shown by specific but partial ablation of FSH-producing cells after induction by gancyclovir and acyclovir. In the ovary, tk protein was localized to the same compartments as the endogenous gonadotropin subunit proteins. This further confirms our finding of ovarian expression of the FSH subunit genes.

Transcriptome Profiling of Granulosa and Theca Cells During Dominant Follicle Development in the Horse1

“…Similarly, earlier efforts failed to detect expression of gonadotropin alpha subunit in ovine ovaries (A.S. McNeilly, unpublished results). In contrast, consistent with the present results in horses, the gonadotropin alpha subunit has reportedly been detected by microarray analyses of human follicular cells [53], and others have reported the presence of gonadotropin alpha and FSH beta subunits in ovarian luteal and interstitial cells of normal adult mice [72]. In the present study, we also sought to determine the presence of gonadotropin beta subunits in equine follicular cells using qPCR.…”

A Comprehensive Survey of the Genes Involved in Maturation and Development of the Rainbow Trout Ovary1

“…1). These findings also are supported by mammalian investigations that demonstrated FSH expression in both ovary [37] and testis [38]. Although evidence exists for the expression of both Cg␣ and LH␤ in the rat testis [39], no corresponding reports, to our knowledge, have appeared for LH␤ expression in the mammalian ovary.…”

Expression of Porcine FSH.BETA. Subunit Promoter-driven Herpes Simplex Virus Thymidine Kinase Gene in Transgenic Rats

“…Previous investigators [21,22] have also reported ectopic expression of the FSHβ subunit and/or HSV-TK gene in tissues other than the pituitary in mice. But in this study, as previously described, we did not detect the transcripts of the FSHβ subunit in the rat gonads (the testis and ovary).…”