title: Measurement of a Comprehensive Sex Steroid Profile in Rodent Serum by High-Sensitive Gas Chromatography-Tandem Mass Spectrometry.
abstract: Accurate measurement of sex steroid concentrations in rodent serum is essential to evaluate mouse and rat models for sex steroid-related disorders. The aim of the present study was to develop a sensitive and specific gas chromatography-tandem mass spectrometry (GC-MS/MS) method to assess a comprehensive sex steroid profile in rodent serum. A major effort was invested in reaching an exceptionally high sensitivity for measuring serum estradiol concentrations. We established a GC-MS/MS assay with a lower limit of detection for estradiol, estrone, T, DHT, progesterone, androstenedione, and dehydroepiandrosterone of 0.3, 0.5, 4.0, 1.6, 8, 4.0, and 50 pg/mL, respectively, whereas the corresponding values for the lower limit of quantification were 0.5, 0.5, 8, 2.5, 74, 12, and 400 pg/mL, respectively. Calibration curves were linear, intra- and interassay coefficients of variation were low, and accuracy was excellent for all analytes. The established assay was used to accurately measure a comprehensive sex steroid profile in female rats and mice according to estrous cycle phase. In addition, we characterized the impact of age, sex, gonadectomy, and estradiol treatment on serum concentrations of these sex hormones in mice. In conclusion, we have established a highly sensitive and specific GC-MS/MS method to assess a comprehensive sex steroid profile in rodent serum in a single run. This GC-MS/MS assay has, to the best of our knowledge, the best detectability reported for estradiol. Our method therefore represents an ideal tool to characterize sex steroid metabolism in a variety of sex steroid-related rodent models and in human samples with low estradiol levels.
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Maria E
authors: ME
authors: Nilsson
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Liesbeth
authors: L
authors: Vandenput
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Åsa
authors: Å
authors: Tivesten
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Anna-Karin
authors: AK
authors: Norlén
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Marie K
authors: MK
authors: Lagerquist
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Sara H
authors: SH
authors: Windahl
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Anna E
authors: AE
authors: Börjesson
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Helen H
authors: HH
authors: Farman
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Matti
authors: M
authors: Poutanen
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Anna
authors: A
authors: Benrick
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Manuel
authors: M
authors: Maliqueo
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Elisabet
authors: E
authors: Stener-Victorin
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Henrik
authors: H
authors: Ryberg
authors: Centre for Bone and Arthritis Research (M.E.N., L.V., M.K.L., S.H.W., A.E.B., H.H.F., M.P., C.O.), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research (Å.T.), Institute of Medicine, Department of Physiology (A.B., M.M., E.S.-V.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-413 45, Sweden; Department of Clinical Chemistry (M.E.N., A.-K.N., H.R.), Sahlgrenska University Hospital, Gothenburg SE-413 45, Sweden; and Department of Physiology (M.P.), Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku FI-20014, Finland.
authors: Claes
authors: C
authors: Ohlsson
mesh_terms: D000735:Androstenedione / Q000032:analysis / Q000097:blood; D000818:Animals; D003687:Dehydroepiandrosterone / Q000032:analysis / Q000097:blood; D013196:Dihydrotestosterone / Q000032:analysis / Q000097:blood; D004958:Estradiol / Q000032:analysis / Q000097:blood; D004970:Estrone / Q000032:analysis / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D012739:Gonadal Steroid Hormones / Q000032:analysis / Q000097:blood*; D051379:Mice; D011374:Progesterone / Q000032:analysis / Q000097:blood; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013739:Testosterone / Q000032:analysis / Q000097:blood
chemical_list: D012739:Gonadal Steroid Hormones; D013196:Dihydrotestosterone; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol