title: The influence of structural modification on progesterone and androgen receptor binding of norethisterone. Correlation with nuclear magnetic resonance signals.
abstract: The relative binding affinities (RBA) of eight progestogens structurally derived from 17 alpha-ethinyl-19-nortestosterone (norethisterone) have been estimated a) for the progesterone receptor from human premenopausal endometrium and b) for the androgen receptor in human mammary carcinoma in vitro. Introduction of a methylene group at C-11, a methyl group at C-18, or a double bond between C-15 and C-16 of the norethisterone molecule increases the RBA to the progesterone receptor. As a rough approximation, the substituent effects seem to be additive. RBA to the androgen receptor follows a more complex pattern when norethisterone is structurally modified. An additional methyl at C-18 enhances affinity to the androgen receptor. The double bond between C-15 and C-16 has no effect except when introduced into desogestrel, where it reduces RBA to the lowest value in the study. The methylene group at C-11 increases androgen RBA when present as the only substituent, but reduces androgen RBA when together with any other substituent. The complete assignment of 13C-NMR signals has been achieved for all 8 steroids investigated. The 13C-resonance signal of C-17 shows a correlation with the RBA to the progesterone receptor, and with the progestogen/androgen RBA ratios.
mesh_terms: D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004717:Endometrium / Q000378:metabolism; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009640:Norethindrone / Q000031:analogs & derivatives / Q000378:metabolism*; D011869:Radioligand Assay; D011944:Receptors, Androgen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D009640:Norethindrone