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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.