FUNCTIONS OF 17ß-HYDROXYSTEROID DEHYDROGENASE TYPE 4

Five types of 17β-hydroxysteroid dehydrogenases catalyzing the conversion of estrogens and androgens at position C17 have been identified so far. The porcine peroxisomal 17β-hydroxysteroid dehydro-genase type 4 (17ß-HSD 4) catalyzes the oxidation of estradiol with high preference over the reduction of estrone. The 17ß-HSD 4 reveals only 25 % amino acid similarity with 17ß-HSD 1, 2, 3 and 5 enzymes. The highest levels of 17ß-HSD 4 mRNA transcription and specific activity are found in liver and kidney followed by ovary and testes. In porcine gonads the immunofluorescence assigned the 17ß-HSD 4 to granulosa cells, Leydig and Sertoli cells. A 2.9 kb mRNA codes for an 80 kDa (737 amino acids) protein featuring domains which are not present in the other 17βHSDs. Although five Asn-Xaa-Ser/Thr (Xaa- unspecified amino acid) sites are found in the 80 kDa protein the enzyme is not glycosylated.The 80 kDa protein is N-terminally cleaved to a 32 kDa enzymatically active fragment. Both the 80 kDa and the N-terminal 32 kDa (amino acids 1-323) protein are the first enzymes that are able to perform the dehydrogenase reaction not only with steroids at the C17 position but also with 3-hydroxyacyl-CoA. The central part of the 80 kDa protein (amino acids 324-596) catalyzes the 2-enoyl-acyl-CoA hydratase reaction with high efficiency. The C-terminal part of the 8