Mechanisms of hormone-mediated carcinogenesis of the ovary in mice
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C C Capen1, W G Beamer, B J Tennent
1Jackson Laboratory, Bar Harbor, ME 04609, USA.
Abstract:
Experimental ovarian carcinogenesis has been investigated in inbred and hybrid strains of mice and induced by a diversity of mechanisms including X-irradiation, oocytotoxic xenobiotic chemicals, ovarian grafting to ectopic or orthotopic sites, neonatal thymectomy, mutant genes reducing germ cell populations, and aging. The mechanisms are briefly reviewed whereby disruptions in the function of graafian follicles results in a spectrum of ovarian proliferative lesions including tumors. The findings in mutant mice support the concept of a secondary (hormonally-mediated) mechanism of ovarian carcinogenesis in mice associated with sterility. Multiple pathogenetic factors that either destroy or diminish the numbers of graafian follicles in the ovary result in decreased sex hormone secretion (especially estradiol-17 beta) leading to a compensatory over-production of pituitary gonadotrophins (particularly luteinizing hormone), which places the mouse ovary at an increased risk to develop tumors. The intense proliferation of ovarian surface epithelium and stromal (interstitial) cells with the development of unique tubular adenomas in response to sterility does not appear to have a counterpart in the ovaries of women.
Insights
Ovarian cancer in mice can be triggered by factors that reduce ovarian follicles, leading to hormonal imbalances and tumor development. These hormonal changes, driven by pituitary gonadotropins, increase cancer risk in mice, a mechanism not observed in women.
Area of Science:
- Reproductive Biology
- Oncology
- Genetics
Background:
- Ovarian carcinogenesis research explores various induction methods in mice.
- Disruptions in graafian follicle function are linked to ovarian lesions and tumors.
- Sterility-associated hormonal changes are implicated in mouse ovarian cancer development.
Purpose of the Study:
- To review mechanisms of experimental ovarian carcinogenesis in mice.
- To investigate the role of hormonal mediation in sterility-associated ovarian tumors.
- To compare pathogenetic factors in mouse and human ovarian cancer.
Main Methods:
- Review of experimental models including X-irradiation, chemical agents, grafting, thymectomy, gene mutations, and aging.
- Analysis of hormonal feedback loops involving estradiol and pituitary gonadotropins.
- Examination of ovarian pathology in mutant mice and comparison with human cases.
Main Results:
- Factors diminishing graafian follicles lead to reduced estradiol secretion.
- Compensatory overproduction of luteinizing hormone increases ovarian tumor risk in mice.
- Proliferation of ovarian surface epithelium and stromal cells observed in sterile mice.
Conclusions:
- Hormonally-mediated carcinogenesis associated with sterility is supported by findings in mutant mice.
- Reduced ovarian follicle numbers and altered hormone secretion are key pathogenetic factors.
- Observed mouse ovarian tumors, like tubular adenomas, lack direct counterparts in human ovaries.