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
| Autor: | Claes Ohlsson, Fu-Ping Zhang, Matti Poutanen, Heli Jokela, Liesbeth Vandenput, Pirjo Pakarinen, Laura Kätkänaho, Janne Hakkarainen, Hanna Heikelä |
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| Rok vydání: | 2015 |
| Předmět: |
Male
endocrine system medicine.medical_specialty 17-Hydroxysteroid Dehydrogenases medicine.drug_class Estrous Cycle Estrone Ovary Dehydrogenase Biology Biochemistry HSD17B enzymes Mice chemistry.chemical_compound Pregnancy Internal medicine estrogen polycyclic compounds Genetics medicine Animals Cholesterol Side-Chain Cleavage Enzyme Sexual Maturation Androstenedione Molecular Biology Progesterone fertility Mice Knockout Normal puberty urogenital system Steroid 17-alpha-Hydroxylase Phosphoproteins Luteinization Endocrinology medicine.anatomical_structure chemistry Estrogen Female HSD17B1 Hydroxysteroid Infertility Female hormones hormone substitutes and hormone antagonists Biotechnology |
| Zdroj: | The FASEB Journal. 29:3806-3816 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.14-269035 |
| Popis: | 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.—Hakkarainen, J., Jokela, H., Pakarinen, P., Heikelä, H., Kätkänaho, L., Vandenput, L., Ohlsson, C., Zhang, F.-P., Poutanen, M. 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. |
| Databáze: | OpenAIRE |
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