title: Specific accumulation of 17 alpha-hydroxyprogesterone in microsomal membranes during the process of cytochrome P-450(C-17)-catalysed androgen biosynthesis. A dynamic study of intermediate formation and turnover.
abstract: A complete dynamic analysis of cytochrome P-450(C-17)-catalysed androgen biosynthesis from a single dose of progesterone and 17 alpha-hydroxyprogesterone in a double-label double-substrate experiment was performed in order to elucidate the controversial intermediacy of 17 alpha-hydroxyprogesterone. Label distribution within the steroid fractions as well as in the membrane and buffer compartments yields direct evidence that the endogenously formed 17 alpha-hydroxyprogesterone (which is in an 'intermediate state') accumulates to a higher degree in microsomal membranes than does the exogenously added 17 alpha-hydroxyprogesterone (which is in a 'substrate state') under certain conditions. It is also demonstrated that endogenously formed 17 alpha-hydroxyprogesterone may partly leave the membrane compartment (in terms of a 'leakage' or 'overflow' phenomenon) and is then able to equilibrate with the pool of exogenously added 17 alpha-hydroxyprogesterone. Since only the label distribution in the membrane-associated (but not always in the aqueous) 17 alpha-hydroxyprogesterone pool corresponds to the label distribution in the androgen fraction, it is concluded that only the membrane-associated 17 alpha-hydroxyprogesterone pool is directly accessible to cytochrome P-450(C-17)-catalysed conversion into androgens.
authors.affiliation: Institut für Physiologische Chemie II, Universität Düsseldorf, Federal Republic of Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kühn-Velten
authors.forename: M
authors.initials: M
authors.lastname: Lessmann
authors.forename: M E
authors.initials: ME
authors.lastname: Förster
authors.forename: W
authors.initials: W
authors.lastname: Staib
mesh_terms: D019326:17-alpha-Hydroxyprogesterone; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D002250:Carbon Radioisotopes; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006908:Hydroxyprogesterones / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008954:Models, Biological; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000378:metabolism*; D014316:Tritium
chemical_list: D000728:Androgens; D002250:Carbon Radioisotopes; D006908:Hydroxyprogesterones; D014316:Tritium; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D003577:Cytochrome P-450 Enzyme System