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Publication : Ovarian tumorigenesis in mice transgenic for murine inhibin alpha subunit promoter-driven Simian Virus 40 T-antigen: ontogeny, functional characteristics, and endocrine effects.

First Author  Rahman NA Year  2001
Journal  Biol Reprod Volume  64
Issue  4 Pages  1122-30
PubMed ID  11259258 Mgi Jnum  J:68195
Mgi Id  MGI:1932242 Doi  10.1095/biolreprod64.4.1122
Citation  Rahman NA, et al. (2001) Ovarian Tumorigenesis in Mice Transgenic for Murine Inhibin alpha Subunit Promoter-Driven Simian Virus 40 T-Antigen: Ontogeny, Functional Characteristics, and Endocrine Effects. Biol Reprod 64(4):1122-30
abstractText  We previously reported formation of ovarian granulosa cell tumors with 100% penetration in a transgenic mouse model with murine inhibin alpha subunit promoter-driven (inhalpha)/Simian Virus 40 T-antigen (Tag). The tumor-bearing inhalpha/Tag mice showed highly elevated serum levels of immunoreactive inhibin. To investigate the onset of tumorigenesis and related endocrine consequences, 6-8 female mice of two inhalpha/Tag lines and their mating control littermates were killed monthly between 1 and 6 mo of age. We also investigated tumorigenesis-related fertility aspects of these two mouse lines. The ontogeny and progression of tumors could be monitored in both inhalpha/Tag lines by alterations of ovarian weights and serum hormone levels. Serum progesterone levels increased in both inhalpha/Tag lines in an age-dependent manner as ovarian tumorigenesis progressed, and a reciprocal decrease occurred in serum LH and FSH. Neither serum estradiol (E(2)) nor uterine weights were significantly altered during tumorigenesis, suggesting that the ovarian tumors represented late stages of granulosa cell differentiation. In conclusion, the present findings show in the inhalpha/Tag TG mice a relation between endocrine consequences of granulosa cell tumorigenesis, and a connection of onset of tumor formation with aberrant steroidogenesis and gonadotropin secretion. These findings indicate that tumors are endocrinologically active and able to exert enhanced negative feedback effects on pituitary function. The tumors provide a good model for endocrinologically active hormone-dependent tumors.
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