PUBLICATION

A novel type of P450c17 lacking the lyase activity is responsible for C21-steroid biosynthesis in the fish ovary and head kidney

Authors
Zhou, L.Y., Wang, D.S., Kobayashi, T., Yano, A., Paul-Prasanth, B., Suzuki, A., Sakai, F., and Nagahama, Y.
ID
ZDB-PUB-100823-2
Date
2007
Source
Endocrinology   148(9): 4282-4291 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Zebrafish
  • Kidney/enzymology*
  • Animals
  • Molecular Sequence Data
  • Steroid 17-alpha-Hydroxylase/genetics*
  • Steroid 17-alpha-Hydroxylase/metabolism
  • Fish Proteins/genetics*
  • Chickens
  • Genome*
  • Fresh Water
  • Fishes
  • Steroids/biosynthesis*
  • Female
  • Ovary/enzymology*
PubMed
17569754 Full text @ Endocrinology
Abstract
Cytochrome P450c17 is the single enzyme that mediates the 17 alpha-hydroxylase and 17, 20 lyase activities during the biosynthesis of steroid hormones in the gonads and adrenal gland. However, the mechanism underlying its dual action continues to be a controversy in the field of steroidogenesis in fish. In an attempt to resolve this issue, we identified a novel type of P450c17 (P450c17-II) by an in silico analysis from the genomes of six fish species. We cloned P450c17-II from tilapia and medaka, and comparison with the conventional P450c17-I revealed that they differ in gene structure and enzymatic activity. Enzymatic assays by thin-layer chromatography revealed that P450c17-II possesses only the 17 alpha-hydroxylase activity without any 17, 20 lyase activity, unlike P450c17-I, which has both these activities. In testis, both P450c17-I and -II express in the interstitial cells. Remarkable differences, revealed by in situ hybridization, in the expression patterns of the P450c17-I and -II in the ovary and head kidney of tilapia during various stages of development strongly suggest that P450c17-I is responsible for the synthesis of estradiol-17beta in the ovary, whereas P450c17-II is required for the production of C21 steroids such as cortisol in the head kidney. More interestingly, a temporally controlled switching is observable in the expression of these two genes during the steroidogenic shift from estradiol-17beta to the C21 steroid, 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (maturation-inducing hormone of fish oocytes) in the fish ovary, revealing a role for P450c17-II in the production of hormones that induce oocyte maturation in fish.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping