Growth-stimulating effect of dienogest, a synthetic steroid, on rodent, canine, and primate mammary glands

We observed hyperplasia of the mammary gland in female beagle dogs, but not in female rats and monkeys, in 91-day toxicity studies on dienogest. In or der to elucidate a possible mechanism for its development and to account fo r this species difference, rye determined the plasma level of growth hormon e (GH in dogs, rats, and monkeys treated orally with dienogest for 91 days. As a result, dogs with mammary hyperplasia showed a prominent, dose-depend ent increase in their GH level; acid, contrarily, rats and monkeys without the hyperplasia of this organ failed to show any such increase. These resul ts were supported by evidence from immunohistochemical and morphometric ana lysis of the pituitary gland. In addition, dienogest and medroxyprogesteron e acetate (MPA) stimulated the growth of canine mammary epithelial cells in the presence of estradiol in vitro, but had no effect on rat and human mam mary epithelial cells incubated under the same conditions. In conclusion, d ienogest with progestational activity caused proliferation of the mammary g land in beagle dogs by increasing the secretion of GH, as do other progesta tional compounds. This change may be partially dependent on the direct effe ct of the drug. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.