Summary
The effects of short-term (8 weeks) treatment with different doses of cyproterone acetate (CPA), levonorgestrel (LN) and progesterone (PRO) on the adrenal gland, ovary, uterus and vagina were studied in cycle-synchronised beagle bitches (first anoestrus). The same organs from non-treated primiparous beagle bitches at the 6th and 9th weeks of pregnancy were also included. In the animals treated with the highest doses of CPA (4.0 mg/kg/day orally) and PRO (42.5mg/kg/day subcutaneously), as well as in pregnant bitches (9th week of pregnancy), a decrease in adrenal weight and cortex width and also an apparent loss of cells in the zona fasciculata and zona reticularis were observed. A marked increase in ovarian weight was recorded only in pregnant bitches (6th week of pregnancy). This was reflected by the presence of multiple well-developed corpora lutea. The ovaries of virgin control and progestagen-treated bitches revealed ovarian atrophy. Progestagen treatment caused marked stimulation of the uterus, resulting in dose-related oedematous and hyperplastic changes. Comparable findings were also observed during pregnancy. The vaginal epithelium of the progestagen-treated and pregnant bitches showed marked mucification as compared with control bitches. These structural responses indicate that progestagen treatment stimulates a pseudopregnancy-like condition in the adrenal glands, uterus and vagina of the beagle bitch.
Abbreviations
- ACTH:
-
Adrenocorticotropin
- CRH:
-
Corticotropin Releasing Hormone
- FSHβ :
-
Follicle Stimulating Hormone Beta Subunit
- LHβ :
-
Luteinizing Hormone Beta Subunit
- MSH:
-
Melanocyte Stimulating Hormone
References
Andersen, A.C., Simpson, M.E.: The ovary and reproductive cycle of the dog (beagle). Los Altos, California: Geron-X, Inc., 1973
Anderson, R.K., Gilmore, C.E., Schnelle, G.B.: Uteroovarian disorders associated with use of medroxyprogesterone in dogs. J. Am. Vet. Med. Assoc. 146, 1311–1316 (1965)
Briggs, M.H.: The beagle dog and contraceptive steroids. Life Sciences 21, 275–284 (1977)
Brodey, R.S., Fidler, I.J.: Clinical and pathological findings in bitches treated with progestational compounds. J. Am. Vet. Med. Assoc. 149, 1406–1415 (1966)
Capel-Edwards, K., Hall, D.E., Fellowes, K.P., Vallance, D.K., Davies, M.J., Lamb, D., Robertson, W.B.: Long-term administration of progesterone to the female beagle dog. Toxicol. Appl. Pharmacol. 24, 3, 474–488 (1973)
El Etreby, M.F., Fath El Bab, M.R.: Effect of cyproterone acetate on cells of the pars distalis of the adenohypophysis in the beagle bitch. Cell Tissue Res. 183, 177–189 (1977)
El Etreby, M.F., Fath El Bab, M.R.: Effect of cyproterone acetate, d-norgestrel and progesterone on cells of the pars distalis of the adenohypophysis in the beagle bitch. Cell Tissue Res. 191, 205–218 (1978)
El Etreby, M.F., Gräf, K.-J.: Effect of contraceptive steroids on mammary gland of beagle dog and its relevance to human carcinogenicity. In: “Pharmacological Methods in Toxicology” (G. Zbinden and F. Gross, eds.) Oxford: Pergamon Press, 1979
El Etreby, M.F., Wrobel, K.-H.: Effect of cyproterone acetate, d-norgestrel and progesterone on the canine mammary gland. Cell Tissue Res. 194, 245–267 (1978)
El Etreby, M.F., Gräf, K.-J., Günzel, P., Neumann, F.: Evaluation of effects of sexual steroids on the hypothalamic-pituitary system of animals and man. Arch. Toxicol. Suppl 2, 11–39 (1979)
Fowler, E.H., Vaughan, T., Gotczik, F., Reichhart, P., Reed, C.: Pathologic changes in mammary glands and uteri from beagle bitches receiving low levels of medroxy-progesterone acetate: an overview of research in progress. In: Pharmacology of Steroid Contraceptive Drugs (S. Garattini and H.W. Berendes eds.) New York: Raven Press, 1977
Girard, J., Baumann, J.B., Graf, S., Hees, G. van, Rosenthal, M., Zuppinger K.: Assessment of ACTH- adrenal activity after treatment with a glucocorticoid and an antiandrogenic steroid. Arch. Toxicol. Suppl., 2, 85–92 (1979)
Goyings, L.S., Sokolowski, J.H., Zimbelman, R.G., Geng, S.: Clinical, morphologic, and clinicopathologic findings in beagles treated for two years with melengestrol acetate. Am. J. Vet. Res. 38, 1923–1931 (1977)
Gräf, K.-J., El Etreby, M.F.: Endocrinology of reproduction in the female beagle dog and its significance in mammary gland tumorigenesis. Acta endocr (Kbh) 89, Suppl. 222: 1–34 (1979)
Jerusalem, C.: Eine kleine Modification der Goldner-(Masson)-Trichromfärbung. Z. wiss. Mikr. 65, 320–321 (1963)
Lubansky, J., King, T.O.: Chronic toxicity study of anapregnone in dogs. Toxicol. Appl. Pharmacol. 7, 489 (1965)
Nelson, L.W., Kelly, W.A.: Progestogen-related gross and microscopic changes in female beagles. Vet. Pathol. 13, 143–156 (1976)
Neumann, F., Bahner, F., Brotherton, J., Gräf, K.-J., Hasan, S.H., Horn, H.F., Hughes, A., Oertel, G.W., Steinbeck, H., Voss, H.E., Wagner, R.K.: Androgens II and Anti-androgens. In: Handbook of Experimental Pharmacology, Vol.XXV/2 (O. Eichler, A. Farah, H. Herken and A.D. Welch, eds.) Berlin, Heidelberg, New York: Springer-Verlag 1974
Owen, L.N., Briggs, M.H.: Contraceptive steroid toxicology in the beagle dog and its relevance to human carcinogenicity Curr. Med. Res. Opin 4, 309–329 (1976)
Sokolowski, J.H., Zimbelman, R.G.: Canine reproduction: Effects of multiple treatments of medroxyprogesterone acetate on reproductive organs in the bitch. Am. J. Vet. Res. 35, 1285–1287 (1974)
Sokolowski, J.H., Zimbelman, R.G., Goyings, L.S.: Canine reproduction: Reproductive organs and related structures of the nonparous, parous, and postpartum bitch. Am. J. Vet. Res. 34, 1001–1013 (1973)
Steiner, G.J., Kistner, R.W., Craig, J.M.: Histological effects of progestins on hyperplasia and carcinoma in situ of the endometrium — further observations. Metabolism 14, 356–386 (1965)
Weikel, J.H., Nelson, L.W.: Problems in evaluating chronic toxicity of contraceptive steroids in dogs. J. Toxicol. Environ. Health 3, 167–177 (1977)
Whitney, J.C.: The pathology of the canine genital tract in false pregnancy. J. Small Anim. Pract. 8, 247–263 (1967)
Wrobel, K.-H., El Etreby, M.F., Günzel, P.: Histochemische und histologische Untersuchungen an der Vagina der Beagle-Hündin während verschiedener Funktionszustände. Acta Histochem. (Jena) 52, 257–270 (1975)
Author information
Authors and Affiliations
Additional information
The author is grateful to Dr. Christel Schöbel and Mrs. P. Kurth for carrying out the experimental work on the animals, to Mrs. B. Schilk and Mrs. U. Tüshaus-Bußmann for their excellent technical assistance, and to Dr. P. Günzel for his advice and encouragement
Rights and permissions
About this article
Cite this article
El Etreby, M.F. Effect of cyproterone acetate, levonorgestrel and progesterone on adrenal glands and reproductive organs in the beagle bitch. Cell Tissue Res. 200, 229–243 (1979). https://doi.org/10.1007/BF00236416
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00236416