Cytochrome P-45017α in β-cells of rat pancreas and its local steroidogenesis

Tadashi Ogishima, Fumiko Mitani, Makoto Suematsu

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11 Citations (Scopus)

Abstract

We have found cytochrome P-45017α 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 β-cells. The enzyme has not only 17α-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 17α-hydroxyprogesterone. Due to a low activity of the built-in lyase, cytochrome P-45017α requires a sufficient electron-transfer from P-450 reductase or presence of an activator to promote the C-C bond cleavage. In β-cells, P-450 reductase was abundant and could efficiently transfer electrons to P-45017α. 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 3β-hydroxysteroid dehydrogenase in β-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, 5α-androstanedione, and dihydrotestosterone, which would act as local steroids in the islets of Langerhans.

Original languageEnglish
Pages (from-to)80-86
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume111
Issue number1-2
DOIs
Publication statusPublished - 2008 Jul 1

Keywords

  • Androgens
  • Androstenedione
  • Cytochrome P-450
  • Islets of Langerhans
  • Local steroids
  • Pancreas
  • β-cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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