This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhou, L.-Y. Articles by Nagahama, Y. Search for Related Content PubMed PubMed Citation Articles by Zhou, L.-Y. Articles by Nagahama, Y.

A Novel Type of P450c17 Lacking the Lyase Activity Is Responsible for C21-Steroid Biosynthesis in the Fish Ovary and Head Kidney

Laboratory of Reproductive Biology (L.-Y.Z., D.-S.W., T.K., A.Y., B.P.-P., A.S., F.S., Y.N.), National Institute for Basic Biology, and School of Life Science (L.-Y.Z., Y.N.), Graduate University for Advanced Studies, Okazaki 444-8585, Japan; SORST (D.-S.W., B.P.-P., A.S., F.S., Y.N.), Japan Science and Technology Corp.; School of Life Science (D.-S.W.), Southwest University, 400715 Chongqing, People’s Republic of China; and National Research Institute of Aquaculture (T.K.), Tamaki, Mie 519-0423, Japan

Address all correspondence and requests for reprints to: Professor Yoshitaka Nagahama, Laboratory of Reproductive Biology, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan. E-mail: nagahama{at}nibb.ac.jp.

Cytochrome P450c17 is the single enzyme that mediates the 17-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-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-17ß 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-17ß to the C21 steroid, 17, 20ß-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.