Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.
Journal article, 2011
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.
pharmacology
Knockout
drug effects
Mice
deficiency
genetics
drug effects
genetics
Hand Strength
RNA
drug effects
Body Weight
Prolactin
physiology
Ovary
Receptors
drug effects
deficiency
Mice
metabolism
Male
physiology
Viscera
genetics
drug effects
Enzyme Activation
Testosterone
drug effects
genetics
Bone and Bones
Animals
Organ Size
Female
Gene Expression Profiling
Membrane Proteins
pathology
Bone Density
genetics
physiology
Forelimb
metabolism
physiology
Isoenzymes
3-Oxo-5-alpha-Steroid 4-Dehydrogenase
physiology
metabolism
physiopathology
metabolism
pathology
metabolism
drug effects
Messenger
Muscle Strength
drug effects
metabolism
blood
Androgens
Orchiectomy
Author
Sara H Windahl
University of Gothenburg
Niklas Andersson
University of Gothenburg
Anna E Börjesson
University of Gothenburg
Charlotte Swanson
University of Gothenburg
Johan Svensson
University of Gothenburg
Sofia Movérare-Skrtic
University of Gothenburg
Klara Sjögren
University of Gothenburg
Ruijin Shao
University of Gothenburg
Jerker Fick
University of Gothenburg
Claes Ohlsson
University of Gothenburg
PLoS ONE
1932-6203 (ISSN) 19326203 (eISSN)
Vol. 6 6 e21402-Subject Categories
Endocrinology and Diabetes
DOI
10.1371/journal.pone.0021402
PubMed
21731732