The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein might play a role in neurogenesis in the central nervous system.
The B Cell Translocation Gene (BTG) Family in the Rat Ovary: Hormonal Induction, Regulation, and Impact on Cell Cycle Kinetics. Li F et al. The B Cell Translocation Gene (BTG) family regulates gene transcription, cellular differentiation, and inhibits proliferation. The present study investigated the spatiotemporal expression pattern of BTG members and their potential role in the rat ovary during the periovulatory period. Immature female rats (22-23 days old) were injected with PMSG to stimulate follicular development. Ovaries or granulosa cells were collected at various times after hCG administration (n=3/time point). Real-time PCR analysis revealed that mRNA for Btg1, Btg2, and Btg3 were highly induced both in intact ovaries and granulosa cells by 4 to 8 h after hCG treatment although their temporal expression patterns differed. In situ hybridization analysis demonstrated that Btg1 mRNA expression was highly induced in theca cells at 4 h after hCG, primarily localized to granulosa cells at 8 h, and decreased at 24 h. Btg2 and Btg3 mRNA was also induced in granulosa cells, however, Btg2 mRNA was observed in newly forming corpora lutea. Inhibition of progesterone action and the EGF pathway did not change Btg1 and Btg2 mRNA expression, whereas inhibition of prostaglandin synthesis or RUNX activity diminished Btg2 mRNA levels. Overexpression of BTG1 or BTG2 arrested granulosa cells at the G0/G1 phase of the cell cycle and decreased cell apoptosis. In summary, hCG induced Btg1, Btg2 and Btg3 mRNA expression predominately in the granulosa cell compartment. Our findings suggest that the induction of the BTG family may be important for theca and granulosa cell differentiation into luteal cells by arresting cell cycle progression.
Identification of Genes Involved in Apoptosis and Dominant Follicle Development During Follicular Waves in Cattle.
Evans AC, et al 2004 hypothesize that granulosa and theca cells from growing dominant follicles, with relatively high intrafollicular concentrations of estradiol, have a greater expression of genes involved in inhibiting apoptosis pathways and lower expression of genes involved in apoptosis pathways than growing subordinate follicles with lower estradiol concentrations. Using the well-characterized bovine dominant follicle model, they collected granulosa and theca cells from individual dominant and the largest subordinate follicle 3 days after initiation of a follicular wave in four animals. Based on ultrasound analysis, both follicle types were in the growth phase at the time of ovariectomy. However, dominant follicles were larger (9.8+/-1.0 versus 7.6+/-0.6 mm in diameter, P<0.05) and had greater intrafollicular concentrations of estradiol ( P<0.05) compared with the largest subordinate follicles. They used bovine cDNA microarrays, which contained a total of 1400 genes including a subset of 53 genes known to be involved in apoptosis pathways, to determine which apoptosis and marker genes from each of the four dominant versus subordinate follicles were potentially differentially expressed. Using a low stringency-screening criterion, 22 genes were identified. Quantitative real-time PCR confirmed that 16 of these genes were differentially expressed. The high intrafollicular concentrations of estradiol in growing dominant follicles were positively associated with enhanced expression of mRNAs in granulosa cells for aromatase, LH receptor, estradiol receptor beta, DICE-1 and MCL-1 compared with granulosa cells from subordinate follicles (all survival-associated genes). In contrast, the relatively low intrafollicular concentrations of estradiol in growing subordinate follicles were positively associated with enhanced expression of mRNAs in granulosa cells for beta glycan, COX-1, TNFalpha, CAD and DRAK-2, and in theca cells for beta glycan, caspase 13, P58(IPK), Apaf-1, BTG-3, and TS-BCLL compared with granulosa or theca cells from dominant follicles (genes that are all associated with cell death and/or apoptosis). These genes may be candidate estradiol target genes and that they may be early markers for the final stages of follicle differentiation and initiation of apoptosis and thus selection of dominant follicles during follicular waves.
Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.