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Ovarian Tumorigenesis in Mice Transgenic for Murine Inhibin Subunit Promoter-Driven Simian Virus 40 T-Antigen: Ontogeny, Functional Characteristics, and Endocrine Effects¹

^a Department of Physiology, University of Turku, 20520 Turku, Finland

ABSTRACT

We previously reported formation of ovarian granulosa cell tumors with 100% penetration in a transgenic mouse model with murine inhibin subunit promoter-driven (inh)/Simian Virus 40 T-antigen (Tag). The tumor-bearing inh/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 inh/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 inh/Tag lines by alterations of ovarian weights and serum hormone levels. Serum progesterone levels increased in both inh/Tag lines in an age-dependent manner as ovarian tumorigenesis progressed, and a reciprocal decrease occurred in serum LH and FSH. Neither serum estradiol (E₂) 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 inh/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.

FOOTNOTES

First decision: 15 August 2000.

¹ This work was supported by a grant from The Academy of Finland and The Finnish Cancer Society.

² Correspondence: Ilpo Huhtaniemi, Department of Physiology, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. FAX: 358 2 2502610; ilpo.huhtaniemi{at}utu.fi

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