Interactions of various 19-nor steroids with human placental microsomal cytochrome P-450 (P-450hpm)

Each of seven 19-nor steroids exhibited the capacity to facilitate the binding of carbon monoxide (CO) to human placental microsomal cytochrome P-450 although quantitative differences were shown to exist. In every case the facilitation was antagonized by androstenedione. 19-Norandrostenedione produced the most pronounced effect followed by 19-nortestosterone, nandrolone decanoate, norethandrolone, norgestrel, norethynodrel and norethindrone in that order. All steroids investigated produced typical type I binding spectra when added to placental microsomes. Scatched plots also indicated binding of each steroid to two sites--a high-affinity, low-capacity binding site and a low-affinity, high-capacity binding site. Correlations between affinity for either site and capacity to facilitate binding of CO to the cytochrome were not observed nor were there good correlations between maximal absorbance differences (approximately390-420 nm) producible and facilitation capacity. It was therefore concluded that no definitive relationships existed between facilitation capacity and qualitative or quantitative aspects of the steroid-binding spectra. The capacity to facilitate CO binding appeared to reside in the absence of a chemical group substituted at the 10 position on molecules of androgenic steroids since all investigated steroids possessing 10-methyl or other 10-substituted groups either had no effect on the CO-binding spectrum or caused a displacement of CO from ferrous heme. In contrast, all steroids studied that lacked a substitution at C-10 (19-nor steroids) produced a facilitating effect on heme-ligand binding.