Abstract
We have previously shown by immunocytochemistry and autoradiography the presence of estrogen receptors (ER) in rhesus monkey ovary. Intense chromogen staining showed specific binding for ER in nuclei of germinal epithelium and granulosa cells of antral follicles; and radiolabeled ligand bound specifically to functional corpora lutea (CL). Although it is accepted that the germinal epithelium of the primate ovary contains ER, some controversy still persists regarding the intraovarian localization of this molecule. In addition, no data exist that localize the aromatic hydrocarbon (dioxin) receptor (AHR), which is known to modulate ER, to the primate ovary. In the present study, we show the presence of ER using Western blot analysis, and ER capable of binding DNA within intraovarian compartments in two species of the genusMacaca (rhesus macaque,Macaca mulatta and stumptail macaque,Macaca arctoides); extend these findings to human ovarian granulosa cells (GC) using Western blot, reverse transcription-polymerase chain reaction (RT-PCR), and gel mobility-shift analysis; and localize the AHR to intraovarian compartments of the macaque ovary by Western blots and gel-shift assays. These experiments strongly suggest that estrogens can exert effects on follicle development directly at the ovary, and provide the first direct evidence that AHR-mediated toxicity may be manifested at the ovary to induce possible antifertility effects.
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References
Barsotti, D. A., Abrahamson, L. J., and Allen, J. R. (1979). Hormonal alterations in female rhesus macaques fed a diet containing 2,3,7,8-tetrachlorodibenzo-p-dioxin.Bull. Environ. Contam. Toxicol. 21, 463–469.
Best, C. L., Pudney, J., Anderson, D. J., and Hill, J. A. (1994). Modulation of human granulosa cell steroid production in vitro by tumor necrosis factor alpha: implications of white blood cells in culture.Obstet. Gynecol. 84, 121–127.
Bettini, E., Pollio, G., Santagati, S., and Maggi, A. (1992). Estrogen receptor in rat brain: presence in the hippocampal formation.Neuroendocrinology 56, 502–508.
Billiar, R. B., Loukides, J. A., and Miller, M. M. (1992). Evidence for the presence of the estrogen receptor in the ovary of the baboon (Papio anubis).J. Clin. Endocrinol. Metabol. 75, 1159–1165.
Blankenship, A. L., Suffia, M. C., Matsumura, F., Walsh, K. J., and Wiley, L. M. (1993). 2,3,7,8-tetrachlrodibenzo-p-dioxin (TCDD) accelerates differentiation of murine preimplantation embryos in vitro.Reprod. Toxicol. 7, 255–261.
Chaffin, C. L. and Hutz, R. J. (1995). Tissue-specific regulation of the aromatic hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in peripubertal female rats.Proc. Endocr. Soc. Washington DC (abstract).
Chaffin, C. L., Roman, B., Peterson, R. E., and Hutz, R. J. (1994). Prenatal exposure to low-dose TCDD alters levels of ovarian estrogen- and dioxin-receptor mRNA in peripubertal rats.Toxicologist 14, 197.
Chaffin, C. L., Peterson, R. E., and Hutz, R. J. (1996).In utero and lactational exposure of female Holtzman rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): modulation of the estrogen signal.Biol. Reprod. 55, 62–67.
Chandrasekher, Y. A., Melner, M. H., Nagalla, S. R., and Stouffer, R. L. (1994). Progesterone receptor, but not estradiol receptor, messenger ribonucleic acid is expressed in luteinizing granulosa cells and the corpus luteum in rhesus monkeys.Endocrinology 135, 307–314.
Cohen, J. H. M., Danel, L., Cordier, G., Saez, S., and Revillard, J.-P. (1983). Sex steroid receptors in peripheral T cells: absence of androgen receptors and restriction of estrogen receptors to OKT8-positive cells.J. Immunol. 131, 2767–2771.
DeVito, J. M., Thomas, T., Umbreit T. H., and Gallo, M. A. (1992). Multi-site regulation of estrogen receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin. In:Relevance of Animal Studies to the Evaluation of Human Cancer Risk. D'Amato, R., Slaga, T. J., Farland, W. H., and Henry, C. (eds.). Wiley-Liss: New York, pp. 321–336.
Dierschke, D. J., Chaffin, C. L., and Hutz, R. J. (1994). Role and site of estrogen action in follicular atresia.Trends Endocrinol. Metab. 5, 215–219.
Dierschke, D. J., Hutz, R. J., and Wolf, R. C. (1985). Induced follicular atresia in rhesus monkeys: strength-duration relationships of the estrogen stimulus.Endocrinology 117, 1397–1403
Dolwick, K. M., Schmidt, J. V., Carver, L. A., Swanson, H. I., and Bradfield, C. A. (1993). Cloning and expression of a human Ah receptor cDNA.Mol. Pharmacol. 44, 911–917.
Giavani, E., Prati, M., and Vismara, C. (1983). Embryonic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin administered to female rats before mating.Environ. Res. 31, 105–110.
Gray, L. E., Jr. and Ostby, J. S. (1995).In utero 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters reproductive morphology and function in female rat offspring.Toxicol. Appl. Pharmacol. 133, 285–294.
Hild-Petito, S. X., Stouffer, R. L., and Brenner, R. M. (1988). Immunocytochemical localization of estradiol and progesterone receptors in the monkey ovary throughout the menstrual cycle.Endocrinology 123, 2896–2905.
Horie, K., Takakura, K., Fujiwara, H., Suginami, H., Liao, S., and Mori, T. (1992). Immunocytochemical localization of androgen receptor in the human ovary throughout the menstrual cycle in relation to oestrogen and progesterone receptor expression.Hum. Reprod. 7, 184–190.
Hurst, B. S., Zilberstein, M., Yang Chou, J., Litman, B., Stephens, J., and Leslie, K. K. (1995). Estrogen receptors are present in human granulosa cells.J. Clin. Endocr. Metab. 80, 229–236.
Hutz, R. J. (1989). Disparate effects of estrogens on in-vitro steroidogenesis by mammalian and avian granulosa cells.Biol. Reprod. 40, 709–713.
Hutz, R. J., Wagner, N., Krause, P., Fisher, C., Syed, N., Dierschke, D. J., Monniaux, D., and Tomanek, M. (1993). Localization of estrogen receptors in rhesus monkey ovary.Am. J. Primatol. 31, 299–309.
Iwai, T., Nanbu, Y., Iwai, M., Fujii, S., and Mori T. (1990). Immunocytochemical localization of oestrogen receptors and progesterone receptors in the human ovary throughout the menstrual cycle.Virchows Arch. Pathol. Anat. 417, 369–375.
Kim, I. and Greenwald, G. S. (1987). Effect of estrogens on follicular development and ovarian and uterine receptors in the immature rabbit, guinea pig, and mouse.Endocr. Jpn. 34, 871–878.
Kuiper, G. G. J. M., Enmark, E., Pelto-Huikko, M., Nilsson, S. and Gustafsson, J.-A. (1996). Cloning of a novel estrogen receptor expressed in rat prostate and ovary.Proc. Natl. Acad. Sci. USA 93, 5925–5930.
Murray, F. J., Smith, F. A., Nitschke, K. D., Humiston, C. G., Kociba, R. J., and Schwetz, B. A. (1979). Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet.Toxicol. Appl. Pharmacol. 50, 241–252.
Peters, L. M. and Wiley, L. M. (1995). Evidence that murine preimplantation embryos express aryl hydrocarbon receptor.Toxicol. Appl. Pharmacol. 134, 214–221.
Poland, A. and Knutson, J. C. (1982). 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity.Ann. Rev. Pharmacol. Toxicol. 22, 517–554.
Rier, S. E., Martin, D. C., Bowman, R. E., Dmowski, W. P., and Becker, J. L. (1993). Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.Fund. Appl. Toxicol. 21, 433–441.
Romkes, M., Piskorska-Pliszczynska, J., and Safe, S. (1987). Effects of 2,3,7,8-tetrachlrodibenzo-p-dioxin on hepatic and uterine estrogen receptor level in rats.Toxicol. Appl. Pharmacol. 87, 306–314.
Schoonmaker, J. N., Bergman, K. S., Steiner, R. A., and Karsch, F. J. (1982). Estradiol-induced luteal regression in the rhesus monkey: evidence for an extraovarian site of action.Endocrinology 110, 1708–1715.
Stouffer, R. L. (1988). Perspectives on the corpus luteum of the menstrual cycle and early pregnancy.Semin. Reprod. Endocrinol. 6, 103–113.
Stouffer, R. L. and Duffy, D. M. (1995). Receptors for sex steroids in the primate corpus luteum.Trends Endocrinol. Metab. 6, 83–89.
Umbreit, T. H. and Gallo, M. A. (1988). Physiological implications of estrogen receptor modulation by 2,3,7,8-tetrachlorodibenzo-p-dioxin.Toxicol. Lett. 42, 5–14.
Westerlind, K. C., Sarkar, G., Bolander, M. E., and Turner, R. T. (1995). Estrogen receptor mRNA is expressed in vivo in rat calvarial periosteum.Steroids 60, 484–487.
White, T. E. K., Rucci, G., Liu, Z., and Gasiewicz, T. A. (1995). Weanling female Sprague-Dawley rats are not sensitive to the antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).Toxicol. Appl. Pharmacol. 133, 313–320.
Wu, T.-C. J., Wang, L., and Wan, Y. Y.-J. (1993). Detection of estrogen receptor messenger ribonucleic acid in human oocytes and cumulus-oocyte complexes using reverse transcriptase-polymerase chain reaction.Fertil. Steril. 59, 54–59.
Zelinski-Wooten, M. B. and Stouffer, R. L. Steroid receptors and action in the primate follicle.Trends Endocrinol. Metab., in press.
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Chaffin, C.L., Heimler, I., Rawlins, R.G. et al. Estrogen receptor and aromatic hydrocarbon receptor in the primate ovary. Endocr 5, 315–321 (1996). https://doi.org/10.1007/BF02739065
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DOI: https://doi.org/10.1007/BF02739065