Cytochrome P-450(17alpha) in beta-cells of rat pancreas and its local steroidogenesis.
We have found cytochrome P-450(17alpha) in the islets of Langerhans of rat pancreas. Its existence coincided with that of insulin and demarcated those of glucagon and somatostatin, demonstrating the localization in beta-cells. The enzyme has not only 17alpha-hydroxylase activity but also lyase one, which is a prerequisite for androgen biosynthesis. The pancreatic microsomes converted progesterone mainly to androstenedione with a minor production of 17alpha-hydroxyprogesterone. Due to a low activity of the built-in lyase, cytochrome P-450(17alpha) requires a sufficient electron-transfer from P-450 reductase or presence of an activator to promote the C-C bond cleavage. In beta-cells, P-450 reductase was abundant and could efficiently transfer electrons to P-450(17alpha). Actually, inhibition with anti-P-450 reductase or limitation of NADPH preferentially reduced the lyase activity. Androstenedione was accumulated when its further metabolism was suppressed. We also found localization of cytochrome P-450scc and 3beta-hydroxysteroid dehydrogenase in beta-cells. These results indicate that the immediate substrate for androgen formation, progesterone, is intracellularly produced and is converted mainly to androstenedione with support by an efficient electron supply from P-450 reductase. The product was supposed to be further metabolized to the reduced derivatives such as testosterone, 5alpha-androstanedione, and dihydrotestosterone, which would act as local steroids in the islets of Langerhans.
Department of Chemistry, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan. oggi@chem.kyushu-univ.jp
Tadashi
T
Ogishima
Fumiko
F
Mitani
Makoto
M
Suematsu
D000818:Animals; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010179:Pancreas / Q000166:cytology* / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013256:Steroids / Q000032:analysis / Q000096:biosynthesis*
D013256:Steroids; D013254:Steroid 17-alpha-Hydroxylase