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Reduced bone mass a...
Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.
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- Windahl, Sara H, 1971 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,University of Gothenburg
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- Andersson, Niklas, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg
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- Börjesson, Anna E (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,University of Gothenburg
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- Swanson, Charlotte, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,University of Gothenburg
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- Svensson, Johan, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,University of Gothenburg
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- Movérare-Skrtic, Sofia (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,University of Gothenburg
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- Sjögren, Klara, 1970 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,University of Gothenburg
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- Shao, Linus Ruijin, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg
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- Lagerquist, Marie (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,University of Gothenburg
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- Fick, Jerker (author)
- Göteborgs universitet,University of Gothenburg
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(creator_code:org_t)
- 2011-06-22
- 2011
- English.
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Abstract
Subject headings
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- Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05) and cortical bone mineral content (-15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
- deficiency
- genetics
- metabolism
- Androgens
- metabolism
- Animals
- Body Weight
- drug effects
- physiology
- Bone Density
- drug effects
- physiology
- Bone and Bones
- pathology
- physiopathology
- Enzyme Activation
- drug effects
- Female
- Forelimb
- drug effects
- physiology
- Gene Expression Profiling
- Hand Strength
- physiology
- Isoenzymes
- genetics
- metabolism
- Male
- Membrane Proteins
- deficiency
- genetics
- metabolism
- Mice
- Mice
- Knockout
- Muscle Strength
- drug effects
- physiology
- Orchiectomy
- Organ Size
- drug effects
- Ovary
- drug effects
- pathology
- RNA
- Messenger
- genetics
- metabolism
- Receptors
- Prolactin
- blood
- genetics
- Testosterone
- pharmacology
- Viscera
- drug effects
- metabolism
- pharmacology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Windahl, Sara H, ...
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Andersson, Nikla ...
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Börjesson, Anna ...
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Swanson, Charlot ...
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Svensson, Johan, ...
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Movérare-Skrtic, ...
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Sjögren, Klara, ...
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Shao, Linus Ruij ...
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Lagerquist, Mari ...
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Ohlsson, Claes, ...
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Fick, Jerker
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Endocrinology an ...
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PloS one
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University of Gothenburg
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Chalmers University of Technology