title: Hydroxysteroid (17β)-dehydrogenase 1-deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production.
abstract: Hydroxysteroid (17β)-dehydrogenase type 1 (HSD17B1) catalyzes the conversion of low active 17-ketosteroids, androstenedione (A-dione) and estrone (E1) to highly active 17-hydroxysteroids, testosterone (T) and E2, respectively. In this study, the importance of HSD17B1 in ovarian estrogen production was determined using Hsd17b1 knockout (HSD17B1KO) mice. In these mice, the ovarian HSD17B enzyme activity was markedly reduced, indicating a central role of HSD17B1 in ovarian physiology. The lack of Hsd17b activity resulted in increased ovarian E1:E2 and A-dione:T ratios, but we also observed reduced progesterone concentration in HSD17B1KO ovaries. Accordingly with the altered steroid production, altered expression of Star, Cyp11a1, Lhcgr, Hsd17b7, and especially Cyp17a1 was observed. The ovaries of HSD17B1KO mice presented with all stages of folliculogenesis, while the corpus luteum structure was less defined and number reduced. Surprisingly, bundles of large granular cells of unknown origin appeared in the stroma of the KO ovaries. The HSD17B1KO mice presented with severe subfertility and failed to initiate pseudopregnancy. However, the HSD17B1KO females presented with normal estrous cycle defined by vaginal smears and normal puberty appearance. This study indicates that HSD17B1 is a key enzyme in ovarian steroidogenesis and has a novel function in initiation and stabilization of pregnancy.
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Janne
authors.initials: J
authors.lastname: Hakkarainen
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Heli
authors.initials: H
authors.lastname: Jokela
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Pakarinen
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Heikelä
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Laura
authors.initials: L
authors.lastname: Kätkänaho
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Vandenput
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Fu-Ping
authors.initials: FP
authors.lastname: Zhang
authors.affiliation: *Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Turku, Finland; and Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden matti.poutanen@utu.fi.
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis / Q000235:genetics; D030762:Estrous Cycle; D005260:Female; D007247:Infertility, Female / Q000201:enzymology* / Q000235:genetics; D034461:Luteinization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis* / Q000235:genetics; D012741:Sexual Maturation / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D015067:17-Hydroxysteroid Dehydrogenases; C532640:PRAP protein, mouse; C576264:hydroxysteroid (17-beta) dehydrogenase 1, mouse; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme
keywords: HSD17B enzymes; estrogen; fertility; ovary