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

More information

Created

10/10/2017