Hyperadrenocorticism is one of the most common endocrine diseases in dogs. In about 85% of cases, the disease is associated with a pituitary tumor, producing excess ACTH. Trilostane, a competitive inhibitor of 3-beta hydroxysteroid dehydrogenase (3[beta]-HSD), has become the medical treatment of choice in Europe for dogs with a pituitary lesion. 3[beta]-HSD is the main enzyme in the metabolism pathway from pregnenolone (P5) to progesterone or dehydroepiandrosterone (DHEA) to androstendione. It is generally known that in various species, like humans, rats and mice there are different types of 3[beta]-HSD present. According to literature the effect of trilostane in different species is contradictory. Although trilostane is frequently used as therapy in dogs, the mechanism of trilostane on the canine steroidogenesis is still unknown.
Thus the goal of the study was to examine the precise and isolated steroid hormone metabolism in canine adrenal glands and corpora lutea under the influcence of trilostane in an in vitro model to improve the medication (therapy) in dogs.
The 3[beta]-HSD activity was studied using radioactive P5 or DHEA as substrate, in order to determine the metabolism of P5 and DHEA in the two types of tissue under the influence of trilostane. Thin layer chromatography was used for separation. And autoradiography for identification of the radioactive metabolites. Furthermore we measured the glucocorticoid metabolites in the tissue supernatant by using enzymimmunoassay (EIA).
The adrenal glands and corporae lutea showed high metabolic activity and a multitude of metabolites were formed. Trilostane decreased the pregnenolone metabolism in vitro dose and time dependently, while DHEA metabolism and hormone metabolism in the corporae lutea stayed uninfluenced. However, in the EIA we could not show any statistical influence of trilostane on the canine adrenal steroidogenesis. A reason therefore could be the low number of cases. Therefore we conclude that there are at least two isoforms also present in dogs. We could show in the in vitro study that there are at least two types of 3[beta]-HSD also in dogs. Further research is need based on these findings.