Comparison of the histological changes in the dog after treatment with the progestins medroxyprogesterone acetate and proligestone

Abstract

Administration of progestins im the dog may result in overproduction of growth hormone, suppression of the hypothalamic-pituitary-adrenocortical axis, and insulin resistance. In this paper we present a comparison of the histological findings in control dogs and dogs treated with either medroxyprogesterone acetate (MPA) or proligestone (PROL). Depot preparations of MPA or PROL were administered (SC) at 3-week intervals in two groups of seven ovario-hysterectomized beagle dogs, after which three dogs of each group were killed. After a 6-month period without hormone treatment during which recovery was studied, the remaining dogs received five additional injections at the same interval and were subsequently killed. Tissue samples of four intact female beagle dogs served as controls. Progestin treatment resulted in atrophy of the adrenal cortex. In both MPA- and PROL-treated dogs, the thickness of the combined zona fasciculata and reticularis was significantly smaller than in control animals. In the mammary glands of progestin-treated dogs there were well developed alveoli and normal ducts adjacent to foci of hyperplastic ductular epithelium. Five dogs in each treatment group had developed benign mammary tumours which varied from simple tubular and papillary adenomas to benign complex and mixed tumours, whereas no mammary tumours were observed in the control animals. In each treatment group, steroid-induced hepatopathy was observed in the liver of three dogs. Vacuolation of the cells of the islets of Langerhans and the epithelium of the intercalated ducts was present in two dogs of each treatment group and was only observed after the second series of progestin administrations. Incidental findings included chronic pyelonephritis, aspecific dermatitis, and mucinous dysplasia of the gall bladder. No abnormalities were found in sections of spleen, lung, brain, or pituitary gland. There were no significant differences in the frequencies of the various abnormalities between MPA- and PROL-treated dogs. Our findings correspond with the clinical and biochemical results after treatment of dogs with MPA and PROL. The high incidence of mammary tumours might be associated with our recent finding that in the dog progestins induce ectopic production of growth hormone in the mammary gland. The dog might be a good model for further studies on hormonally induced breast cancers.