This proposal deals with the synthesis of pregnenolone, the precursor to progesterone and its inhibition in vitro and in vivo. The in vitro studies will involve the purification and characterization of corpus luteum cytochrome P-450. The interactions at the active site will be studied by equilibrium binding, optic and paramagnetic spectral techniques with radioactive and spin-labeled substrate and inhibitor analogs. Other studies will deal with the target effects of the progesterone molecule including its binding energies and those of monosubstituted congeners. Appropriate substances of potential pharmacologic significance will be assessed further by bioassay. Purification of placental aromatase will also be undertaken and characteristics of the purified protein and its substrate and inhibitor sites will be studied.
| Seeley, D; Schleyer, H; Kashiwagi, K et al. (1987) Studies of the active site of cytochrome P-450scc with a high-affinity spin-labeled inhibitor. Biochemistry 26:1270-5 |
| Seeley, D H; Wolfson, A J; Hourihan, J et al. (1985) Inhibition of iron-sulfur protein-mediated reduction of cytochrome P-450SCC by specific antibodies. Endocrinology 116:2008-12 |
