title: Transgenic male mice expressing human hydroxysteroid dehydrogenase 2 indicate a role for the enzyme independent of its action on sex steroids.
abstract: Hydroxysteroid (17beta) dehydrogenase 2 (HSD17B2) has been shown to inactivate both estrogens and androgens and activate 20alpha-hydroxyprogesterone to progesterone. In the present study, we generated transgenic (TG) mice ubiquitously expressing human HSD17B2. The TG mice produced showed growth retardation and delayed eye opening at the postnatal age. Disrupted spermatogenesis was evident in the presence of normal serum and intratesticular testosterone, progesterone, and normal circulating LH concentrations. A proper androgen action in the target tissues was confirmed by normal histological appearance of the prostate and epididymis. Furthermore, quantitative RT-PCR analysis indicated only a slight decrease in androgen-dependent gene expression in the prostate. The disrupted spermatogenesis was not associated with increased germ cell apoptosis as analyzed by caspase-3 activation. However, it resulted in infertility in the HSD17B2 TG males after the age of 3 months, and at the age of 6 months the seminiferous tubules showed a Sertoli cell-only phenotype. The data indicate that the growth retardation and disrupted spermatogenesis are not due to a lack of proper estrogen or androgen action. Interestingly, the testicular phenotype and some of the other phenotypic changes described are typically observed in mice with reduced action of retinoic acid signaling. This, together with the rescue of the testis phenotype by a synthetic retinoic acid receptor agonist (4-[(E)-2-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid), suggests a role for HSD17B2 in the action of retinoids, in addition to its oxidative HSD17B activity on sex steroids.
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland.
authors.forename: Shen
authors.initials: S
authors.lastname: Zhongyi
authors.forename: Pia
authors.initials: P
authors.lastname: Rantakari
authors.forename: Tarja
authors.initials: T
authors.lastname: Lamminen
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D000199:Actins / Q000235:genetics; D000818:Animals; D001835:Body Weight; D002645:Chickens; D004960:Estradiol Dehydrogenases; D005280:Fenoterol; D005298:Fertility; D005640:Follicle Stimulating Hormone / Q000097:blood; D006130:Growth Disorders / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D011374:Progesterone / Q000097:blood*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011944:Receptors, Androgen / Q000378:metabolism; D012726:Sexual Behavior, Animal; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000201:enzymology* / Q000473:pathology; D013739:Testosterone / Q000097:blood*
chemical_list: D000199:Actins; D011944:Receptors, Androgen; D005280:Fenoterol; D013739:Testosterone; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015067:17-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human