title: Binding specificity of medroxyprogesterone acetate and proligestone for the progesterone and glucocorticoid receptor in the dog.
abstract: The use of the synthetic progestin medroxyprogesterone acetate (MPA) for estrus prevention in the dog can result in overproduction of growth hormone, suppression of plasma glucocorticoid levels, and the induction of mammary tumors. Proligestone (PROL) was claimed to be devoid of these unwanted side effects. In the present study, the binding characteristics of MPA and PROL for the canine progesterone receptor (PR) and glucocorticoid receptor (GR) were investigated. The apparent inhibition 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 order for displacement of the binding of the PR ligand [3H]ORG 2058 from the canine uterine receptor was: MPA approximately ORG 2058 > PROL > progesterone >> cortisol, dexamethasone, and spironolactone. The rank order for displacement of the specific binding of the GR ligand [3H]dexamethasone from the canine liver receptor was: dexamethasone > cortisol > MPA > PROL > progesterone >> aldosterone approximately spironolactone. The apparent inhibition constants of PROL for both the PR and the GR were approximately 10 times higher than those of MPA. The ratios of the inhibition constants for the GR and PR appeared to be equal for PROL and MPA. It is concluded that although MPA has higher affinities for the PR and GR than PROL, both progestins have a similar in vitro 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.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Utrecht University, Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Selman
authors.forename: J
authors.initials: J
authors.lastname: Wolfswinkel
authors.forename: J A
authors.initials: JA
authors.lastname: Mol
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000378:metabolism; D004285:Dogs; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000378:metabolism*; D011374:Progesterone / Q000031:analogs & derivatives* / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D014316:Tritium
chemical_list: D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D014316:Tritium; D011374:Progesterone; C017677:proligestone; D003907:Dexamethasone; D017258:Medroxyprogesterone Acetate; D006854:Hydrocortisone