Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice

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....

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Veröffentlicht in:	PloS one 2011, Vol.6 (6), p.e21402-e21402
Hauptverfasser:	Windahl, Sara H, Andersson, Niklas, Börjesson, Anna E, Swanson, Charlotte, Svensson, Johan, Movérare-Skrtic, Sofia, Sjögren, Klara, Shao, Ruijin, Lagerquist, Marie K, Ohlsson, Claes
Format:	Artikel
Sprache:	eng
Schlagworte:	3-Oxo-5-alpha-Steroid 4-Dehydrogenase 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - deficiency 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - metabolism Androgen receptors Androgens Androgens - metabolism Animal tissues Animals Arthritis Biology blood Body Weight Body Weight - drug effects Body Weight - physiology Bone (cortical) Bone (trabecular) Bone and Bones Bone and Bones - pathology Bone and Bones - physiopathology Bone Density Bone Density - drug effects Bone Density - physiology Bone mass Bone mineral content Bone mineral density Cancellous bone Clinical medicine Coding Cortical bone deficiency Dihydrotestosterone Drug dosages drug effects Endocrinology and Diabetes Endokrinologi och diabetes Enzyme Activation Enzyme Activation - drug effects Enzymes Estrogens Female Females Forelimb Forelimb - drug effects Forelimb - physiology Gene Expression Profiling genetics Grip strength Hand Strength Hand Strength - physiology Insulin-like growth factors Isoenzymes Isoenzymes - genetics Isoenzymes - metabolism Knockout Liver Male Males Medicine Membrane Proteins Membrane Proteins - deficiency Membrane Proteins - genetics Membrane Proteins - metabolism Messenger Metabolism Mice Mice, Knockout Muscle Strength Muscle Strength - drug effects Muscle Strength - physiology Nitric oxide Orchiectomy Organ Size Organ Size - drug effects Ovary Ovary - drug effects Ovary - pathology pathology pharmacology physiology physiopathology Polycystic ovary syndrome Prolactin Prostate Receptors Receptors, Prolactin - blood Receptors, Prolactin - genetics Regulators RNA RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Steroid 5α-reductase Testosterone Testosterone - pharmacology Viscera Viscera - drug effects Viscera - metabolism
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Zusammenfassung:	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
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0021402