BINDING-SPECIFICITY OF MEDROXYPROGESTERONE ACETATE AND PROLIGESTONE FOR THE PROGESTERONE AND GLUCOCORTICOID RECEPTOR IN THE DOG

The use of the synthetic progestin medroxyprogesterone acetate (MPA)So r estrus prevention in the dog can result in overproduction of growth hormone, suppression of plasma glucocorticoid levels, and the inductio n of mammary tumors. Proligestone (PROL) was claimed to be devoid of t hese these unwanted side effects. In the present study, the binding ch aracteristics of MPA and PROL for the canine progesterone receptor (PR ) and glucocorticoid receptor (GR) were investigated. The apparent inh ibition constants for the PR and GR of MPA and PROL were compared with those of progesterone, ORG 2058, and a number of corticosteroids. MPA and PROL had high affinities for both the PR and the GR. The rank ord er for displacement of the binding of the PR ligand [H-3]ORG 2058 from the canine uterine receptor was: MPA approximate to ORG 2058 > PROL > progesterone >> cortisol dexamethasone, and spironolactone. The rank order for displacement of the specific binding of the GR ligand [H-3]d examethasone from the canine liver receptor was: dexamethasone > corti sol > MPA > PROL > progesterone >> aldosterone approximate to spironol actone. The apparent inhibition constants of PROL far both the PR and the GR were approximately 10 times higher than those of MPA. The ratio s of the inhibition constants for the GR and PR appeared to be equal f or PROL and MPA. It is concluded that although MPA has higher affiniti es for the PR and GR than PROL, both progestins have a similar in vitr o binding specificity, which is less than that of progesterone. These findings are consistent with suppression of the adrenal cortex and the induction of growth hormone secretion in the mammary gland after MPA and PROL treatment in dogs.