Induction of Epithelial Neoplasms in the Ovaries of Guinea Pigs by Estrogenic Stimulation

Silva, E. G.; Tornos, Carmen; Deavers, Michael T.; Kaisman, K.; Gray, Kenneth N.; Gershenson, David M.

doi:10.1006/gyno.1998.5153

Cited by 80 publications

(59 citation statements)

References 12 publications

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“…Aberrant hormonal profiles have been suggested as a mechanism for ovarian cysts by several authors [6,46,47,52]. In the present study, passive immunization against the inhibin α-subunit increased ovarian weights in a dosedependent manner.…”

Section: Discussionsupporting

confidence: 68%

Serous Cysts Are a Benign Component of the Cyclic Ovary in the Guinea Pig with an Incidence Dependent upon Inhibin Bioactivity.

et al. 2002

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ABSTRACT. Ovaries were collected from normal cycling female guinea pigs on each day of the estrous cycle (n=5 per day) for histological analysis of ovarian morphology. Three types of ovarian cysts were observed: serous cysts, follicular cysts and parovarian cysts. The most common were serous cysts (cystic rete ovarii), which were present throughout the estrous cycle with an overall incidence of 63.5% (54 out of 85 animals). Follicular cysts occurred in 22.4% of guinea pigs overall (19 out of 85). Only one parovarian cyst (1 out of 85) was observed in the present experiment. Follicular cysts always coincided with serous cysts and were less common during diestrus. The incidence of serous cysts did not vary significantly across the estrous cycle. In a second experiment, cycling female guinea pigs were arrested in a prolonged luteal phase by a progesterone implant in order to achieve ovarian synchrony. They were then treated with inhibin antiserum (0.5 or 1 ml per animal i.v.; n=6 per group) or normal goat serum (controls; n=6 per group). There was a dose dependent increase in the incidence of serous ovarian cysts following passive immunization against the inhibin α-subunit. These results suggest that serous cysts are a normal component of the cyclic guinea pig ovary and that alterations in the inhibin-follicle-stimulating hormone system appear to modulate the incidence of serous ovarian cysts in this species. KEY WORDS: guinea pig, inhibin, ovarian cyst, passive immunization, serous cyst.

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Section: Discussionsupporting

confidence: 68%

Serous Cysts Are a Benign Component of the Cyclic Ovary in the Guinea Pig with an Incidence Dependent upon Inhibin Bioactivity.

et al. 2002

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“…All of the hormones were administered for 12 months. The number of animals placed in each group was determined by our previous experience with these hormones (10,11). Larger numbers of animals were placed in the groups receiving hormones likely to induce calcifications, whereas a smaller number of animals received the hormones that were less likely to induce calcifications, or hormones that were difficult to obtain, such as prolactin and growth hormone.…”

Section: Methodsmentioning

confidence: 99%

Calcifications in Ovary and Endometrium and Their Neoplasms

et al. 2003

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In this study, we investigated the role of hormones in the pathogenesis of calcifications in ovary and in endometrium and their neoplasms of the gynecologic tract and assessed the anatomic location and incidence of these calcifications. The study consists of three parts designed to investigate the pathogenesis, the location, and the incidence of calcifications in ovary and endometrium and their neoplasms. In the first part, 79 female guinea pigs were divided into 10 groups, and different hormones, given weekly for 12 months, were administered to the guinea pigs by group. A control group of 7 guinea pigs received sterile water. Calcifications developed in 5 of 7 guinea pigs treated with prolactin, 10 of 20 treated with human chorionic gonadotropin, 5 of 11 treated with estradiol, 3 of 7 treated with estrone, 1 of 6 treated with growth hormone, and 1 of 10 treated with testosterone; in 20 of the guinea pigs, the calcifications developed in the stroma of the endometrium, and in 5 guinea pigs, they developed in the ovary. The second part of the study consisted of an evaluation of the specific location of calcifications in 43 consecutive human surgical ovaries and endometria. Calcifications were seen only in the stroma in 100% of the ovarian serous adenofibroma specimens; in ovarian serous borderline neoplasms, the stroma contained 70 to 100% of the calcifications, and the epithelium had 0 to 30% of the calcifications. In ovarian serous carcinoma specimens, the calcifications were seen in the stroma in 50 to 60% of the cases, in the epithelium in 40% of the cases, and in areas of necrosis in 10% of the cases.The third part of the study was directed to determine the frequency of calcifications in ovarian lesions. We found that all cases of endosalpingiosis and ovarian low-grade serous carcinoma had calcifications, whereas 80% of the cases of serous borderline tumor had calcifications, and only 50% of the cases of ovarian high-grade serous carcinoma contained calcifications. The results of this study indicate that the majority of the calcifications in the ovary and the endometrium and their neoplasms are present in the stroma. This is most probably secondary to metabolic changes, which could be related to hormones and not caused by degenerative changes in epithelial cells. Pathologic calcifications are classified as either metastatic (associated with hypercalcemia) or dystrophic (associated with normal calcemia) (1, 2). Traditionally, calcifications in neoplasms have been considered to be dystrophic, forming secondary to degeneration of the epithelium or in association with areas of necrosis (2-6). However, a secretory rather than a degenerative etiology has also been suggested on the basis of the absence of stainable DNA and RNA in areas with calcifications (7-9). In this study, we investigated the role of hormones in the pathogenesis of calcifications in the ovary and the endometrium and their neoplasms and assessed the anatomic site and incidence of these calcifications. A novel pathogenetic mechanism to explain the...

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“…Androgens increase cell proliferation and decrease cell death in ovarian tissue, indicating a cancer-promoting effect [43]. Women with elevated serum levels of androgens have an increased risk of ovarian cancer [44,45], and androgen administration is associated with ovarian cancer in animal models [46]. Ovarian cancer is associated with an increase in androgen production [47].…”

Section: Introductionmentioning

confidence: 99%

The androgen receptor and prostate cancer: A role for sexual selection and sexual conflict?

Summers

Crespi

2008

Medical Hypotheses

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Summary We propose and evaluate the hypothesis that the CAG repeat region of the androgen receptor represents a locus of antagonistic pleiotropy in the context of sexual selection and sexual conflict. Short repeats are associated with increased transactivation of the androgen receptor at the molecular level, and increased fertility at the phenotypic level. However, short repeats are also associated with increased risk of prostate cancer, and with more aggressive forms of the disease. The somatic evolution of cancer cell lineages also shows a repeated pattern of shortening of the CAG repeat in association with cancer progression, apparently as a result of positive selection among cell lineages. We further postulate that other genes associated with prostate cancer are likely to mediate antagonistic pleiotropy in the context of sexual selection and sexual conflict. A key prediction of this hypothesis is that the genes mediating antagonistic pleiotropy will show historical evidence of positive selection, particularly in the context of sexual conflict. Previous research on the molecular evolution of specific genes associated with prostate cancer supports this prediction, and we suggest further critical tests of the role for genomic conflicts and tradeoffs in the evolution of cancer risk.

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Induction of Epithelial Neoplasms in the Ovaries of Guinea Pigs by Estrogenic Stimulation

Cited by 80 publications

References 12 publications

Serous Cysts Are a Benign Component of the Cyclic Ovary in the Guinea Pig with an Incidence Dependent upon Inhibin Bioactivity.

Serous Cysts Are a Benign Component of the Cyclic Ovary in the Guinea Pig with an Incidence Dependent upon Inhibin Bioactivity.

Calcifications in Ovary and Endometrium and Their Neoplasms

The androgen receptor and prostate cancer: A role for sexual selection and sexual conflict?

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