Feil P D, Miljković M, Bardin C W
Endocrinology. 1976 Jun;98(6):1508-15. doi: 10.1210/endo-98-6-1508.
The guinea pig progestin receptor appears to be unique among mammalian receptors studied to date in that it displays a low binding affinity for some biologically potent 17 alpha-substituted progestinss. [3H]Medroxyprogesterone acetate (MPA) was synthesized and used to investigate this dichotomy between binding affinity and biological activity. The comparison of cytoplasmic and nuclear receptor binding characteristics suggested that progesterone and MPA were bound to the same receptor but with different affinities. Following an intravenous injection of 3H-steroids, the plasma level of progesterone was lower than that of MPA at all time points. Correspondingly, for up to 6 hours following steroid administration, progesterone levels were lower in uterine cytoplasm and higher in nuclei than those of MPA. However, by 24 hours, MPA nuclear levels were higher than those of progesterone, in accordance with plasma levels. We conclude that the potent biological activity of MPA relative to progesterone is due in part to its slower rate of metabolism and longer nuclear retention.
豚鼠孕激素受体在迄今为止所研究的哺乳动物受体中似乎是独特的，因为它对某些具有生物活性的17α-取代孕激素显示出低结合亲和力。合成了[3H]醋酸甲羟孕酮（MPA）并用于研究这种结合亲和力与生物活性之间的二分法。细胞质和核受体结合特性的比较表明，孕酮和MPA与同一受体结合，但亲和力不同。静脉注射3H-类固醇后，在所有时间点孕酮的血浆水平均低于MPA。相应地，在给予类固醇后长达6小时，子宫细胞质中的孕酮水平低于MPA，而细胞核中的孕酮水平高于MPA。然而，到24小时时，MPA的核水平高于孕酮，这与血浆水平一致。我们得出结论，MPA相对于孕酮的强大生物活性部分归因于其较慢的代谢速率和较长的核滞留时间。
