生物活性

• 描述Progesterone Receptor (PGR) is a member or the steroid receptor superfamily. It mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. Progesterone Receptor is involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. Norethindrone, also termed Norethisterone (NET) is a synthetic 19-nortestosterone derivative. Norethindrone acts as a ligand that binds to progesterone receptor. According to published data, mean of relative binding affinity (RBA) values of norethisterone to the progesterone, androgen and estrogen receptor in cytosol of human breast MCF-7 cells and to the glucocorticoid receptor in that of leukemic IM-9 cells were 21.5%, 3.2%, not binding, and 0.8%, respectively. These data were all expressed as percentage of standard ligands of Org 2058, 5a-dihydrotestosterone (DHT), estradiol (E2) and dexamethasone (Dex), respectively. Mean of relative agonistic activity (RAA) values of norethisterone to the progesterone, androgen, estrogen and glucocorticoid receptor in transactivation assays with CHO cells using Org 2058, 5a-dihydro-testosterone (DHT), estradiol (E2) and dexamethasone (Dex) as standards were also measured. The data (also expressed as percentage of standard ligands) were 12.4%, and 1.1% respectively for the progesterone and androgen receptor, while no transactivation was detected for the estrogen or glucocorticoid receptor. According to cell proliferation data measured by an ATP-chemosensitivity test, norethisterone inhibited MCF-7 cells proliferation between 23% and 41% over the concentration range of 0.01 nM to 10 μM tested. In vivo, the mean active doses (MAD) of norethisterone in progestagenic (McPhail), androgenic (Hershberger), estrogenic (Allen–Doisy) tests, and in a progestagenic and estrogenic (ovulation inhibition test) were 0.063 mg/kg, 2.5 mg/kg, 4 mg/kg and 0.235 mg/kg respectively after subcutaneous administration and 0.25 mg/kg, 20 mg/kg, 8 mg/kg and 12 mg/kg respectively after oral administration.

• 动物研究
  剂量	Rat: 10 mg/kg, 50 mg/kg[3] (p.o.), 8 mg/kg[2] (p.o.); 4 mg/kg[2] (s.c.)
  给药途径	p.o., s.c.