Selman P J, Wolfswinkel J, Mol J A
Department of Clinical Sciences of Companion Animals, Utrecht University, Netherlands.
Steroids. 1996 Mar;61(3):133-7. doi: 10.1016/0039-128x(95)00216-d.
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.
使用合成孕激素醋酸甲羟孕酮（MPA）来预防犬类发情可能会导致生长激素分泌过多、血浆糖皮质激素水平受到抑制以及诱发乳腺肿瘤。炔诺孕酮（PROL）据称没有这些不良副作用。在本研究中，对MPA和PROL与犬孕酮受体（PR）和糖皮质激素受体（GR）的结合特性进行了研究。将MPA和PROL对PR和GR的表观抑制常数与孕酮、ORG 2058以及多种皮质类固醇的表观抑制常数进行了比较。MPA和PROL对PR和GR都具有高亲和力。从犬子宫受体上置换PR配体[3H]ORG 2058结合的顺序为：MPA约等于ORG 2058 > PROL > 孕酮 >> 皮质醇、地塞米松和螺内酯。从犬肝受体上置换GR配体[3H]地塞米松特异性结合的顺序为：地塞米松 > 皮质醇 > MPA > PROL > 孕酮 >> 醛固酮约等于螺内酯。PROL对PR和GR的表观抑制常数比MPA的表观抑制常数大约高10倍。PROL和MPA的GR与PR抑制常数之比似乎相等。结论是，尽管MPA对PR和GR的亲和力高于PROL，但两种孕激素具有相似的体外结合特异性，且低于孕酮。这些发现与犬经MPA和PROL治疗后肾上腺皮质受到抑制以及乳腺中生长激素分泌增加是一致的。
