Expression of tumor necrosis factor-stimulated gene-6 in the rat ovary in response to an ovulatory dose of gonadotropin

Current evidence supports the hypothesis that the biochemical events of mam malian ovulation are analogous to an acute inflammatory reaction. This stud y reveals that tumor necrosis factor-stimulated gene-6 (TSG-6), which encod es a member of the superfamily of hyaluronan-binding proteins that is speci fically translated in inflammatory reactions, is expressed in ovarian folli cles that have been induced to ovulate. Immature Wistar rats were primed wi th 10 IU equine CG sc; and 48 h later, the 12-h ovulatory process was initi ated by 10 IU human CG (hCG), sc. Ovarian RNA was extracted at 0, 2, 4. 8, 12. and 24 h after the primed animals were injected with hCG. The RNA extra cts were used for RT-PCR differential display of amplified complementary DN As (cDNAs) that represented gene expression in the stimulated ovarian tissu e. Northern analysis of one of the differentially amplified cDNAs confirmed that it was part of a gene that was substantially up-regulated at 4-8 h af ter the ovaries had been stimulated by hCG. Subcloning and sequence analysi s revealed that the cDNA matched the gene for TSG-6. In situ hybridization indicated that the TSG-6 messenger RNA was primarily located in the cumulus mass and the antral granulosa cells of large ovarian follicles. In conclus ion, the data show that expression of TSG-6 is an integral part of the casc ade of inflammatory-like changes that occur in an ovulatory follicle in res ponse to a trophic hormone that couples with luteinizing hormone/hCG recept ors.