COMPARISON OF THE HISTOLOGICAL-CHANGES IN THE DOG AFTER TREATMENT WITH THE PROGESTINS MEDROXYPROGESTERONE ACETATE AND PROLIGESTONE

Administration of progestins in the dog may result in overproduction o f growth hormone, suppression of the hypothalamic-pituitary-adrenocort ical axis, and insulin resistance. In this paper we present a comparis on 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 interval s in two groups of seven ovario-hysterectomized beagle dogs, after whi ch three dogs of each group were killed. After a 6-month period withou t hormone treatment during which recovery was studied, the remaining d ogs 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 adr enal cortex. In both MPA- and PROL-treated dogs, the thickness of the combined zona fasciculata and reticularis was significantly smaller th an in control animals. In the mammary glands of progestin-treated dogs there were well developed alveoli and normal ducts adjacent to foci o f 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 treatme nt group, steroid-induced hepatopathy was observed in the liver of thr ee dogs. Vacuolation of the cells of the islets of Langerhans and the epithelium of the intercalated ducts was present in two dogs of each t reatment group and was only observed after the second series of proges tin administrations. Incidental findings included chronic pyelonephrit is, aspecific dermatitis, and mucinous dysplasia of the gall bladder. No abnormalities were found in sections of spleen, lung, brain, or pit uitary 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 tr eatment of dogs with MPA and PROL. The high incidence of mammary tumou rs might be associated with our recent finding that in the dog progest ins induce ectopic production of growth hormone in the mammary gland, The dog might be a good model for further studies on hormonally induce d breast cancers.