abstract
Although California sea lions are perhaps one of the best studied pinnipeds species, relatively little is known about endocrine regulation of the reproductive cycle. Reproductive tract tumors, however, are common in free-ranging subadult and adult sea lions. Approximately 18 % of subadult and adult sea lions stranding on the central California, USA coast are diagnosed with urogenital carcinomas, which arise in the vagina or cervix in females and the penis, prepuce, or urethra in males.1 Leiomyomas are most commonly diagnosed in the uterus of multiparous females. Given that urogenital tumors arise in tissues subject to continuous hormonal influence, gaining a better understanding of the cyclic hormone induced changes that occur in the reproductive tract throughout the breeding cycle is important. These studies were part of a larger investigation on the pathogenesis of sea lion urogenital carcinoma. Normal morphology and immunohistochemical expression of estrogen receptor α (ER) and progesterone receptor (PR) were defined throughout the female and male reproductive tract. In addition, immunohistochemical expression of ER α and PR were evaluated in sea lions with urogenital carcinoma, intraepithelial urogenital carcinoma ("early neoplasia"), and leiomyomas.
During large portions of the breeding cycle, ovaries contained corpora lutea (CLs) and variably developed follicles. Uterine morphology suggested estrogen influence during the summer pupping and estrus period and throughout the spring. Squamous differentiation of cervical and vaginal epithelium occurred during estrus and in the spring. Both ER and PR were expressed throughout reproductive tissues of females and male sea lions including the cervix, vagina, penis, prepuce, and distal urethra where urogenital tumors commonly develop. ER α expression highest during pupping and estrus and in the spring. Cyclic changes in PR expression were minimal.
Estrogen receptor α expression decreased significantly in intraepithelial neoplasia compared to normal genital epithelium and expression in metastatic lesions was completely absent. Expression of PR occurred in neoplastic cells in early intraepithelial neoplasia and in metastatic tumors. In leiomyomas, there was ER α expression in 5 of 8 (62.5 %) tumors and PR expression in 7 of 8 (87.5 %) tumors. These results indicate steroid hormone receptors are commonly expressed throughout male and female reproductive tissues suggesting the potential for these tissues to be responsive to endogenous hormones or chemicals that mimic steroid hormone action.
acknowledgements
We wish to thank the staff and volunteers of The Marine Mammal Center and the VMTH histology laboratory. Funding was provided by the West Coast Center for Oceans and Human Health through the NOAA Oceans and Human Health Initiative and a National Institute of Health, NRSA Environmental Pathology Post Doctoral Fellowship.
References
1. Gulland FM, Trupkiewicz JG, Spraker TR, Lowenstine LJ. 1996. Metastatic carcinoma of probable transitional cell origin in 66 free-living California sea lions (Zalophus californianus), 1979 to 1994. Journal of Wildlife Diseases 32: 250-258.
2. Lipscomb TP, Scott DP, Garber RL, Krafft AE, Tsai MM, Lichy JH, Taubenberger JK, Schulman FY, Gulland FM. 2000. Common metastatic carcinoma of California sea lions (Zalophus californianus): evidence of genital origin and association with novel gammaherpesvirus. Veterinary Pathology 37: 609-617.