Influence of aromatase inhibition on the bone-protective effects of testosterone.
The influence of the aromatase enzyme in androgen-induced bone maintenance after skeletal maturity remains somewhat unclear. Our purpose was to determine whether aromatase activity is essential to androgen-induced bone maintenance. Ten-month-old male Fisher 344 rats (n = 73) were randomly assigned to receive Sham surgery, orchiectomy (ORX), ORX + anastrozole (AN; aromatase inhibitor), ORX + testosterone-enanthate (TE, 7.0 mg/wk), ORX + TE + AN, ORX + trenbolone-enanthate (TREN; nonaromatizable, nonestrogenic testosterone analogue; 1.0 mg/wk), or ORX + TREN + AN. ORX animals exhibited histomorphometric indices of high-turnover osteopenia and reduced cancellous bone volume compared with Shams. Both TE and TREN administration suppressed cancellous bone turnover similarly and fully prevented ORX-induced cancellous bone loss. TE- and TREN-treated animals also exhibited greater femoral neck shear strength than ORX animals. AN co-administration slightly inhibited the suppression of bone resorption in TE-treated animals but did not alter TE-induced suppression of bone formation or the osteogenic effects of this androgen. In TREN-treated animals, AN co-administration produced no discernible effects on cancellous bone turnover or bone volume. ORX animals also exhibited reduced levator ani/bulbocavernosus (LABC) muscle mass and elevated visceral adiposity. In contrast, TE and TREN produced potent myotrophic effects in the LABC muscle and maintained fat mass at the level of Shams. AN co-administration did not alter androgen-induced effects on muscle or fat. In conclusion, androgens are able to induce direct effects on musculoskeletal and adipose tissue, independent of aromatase activity.
Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, FL, USA; Department of Kinesiology, University of Rhode Island, Kingston, RI, USA.
Darren T
DT
Beck
Joshua F
JF
Yarrow
Luke A
LA
Beggs
Dana M
DM
Otzel
Fan
F
Ye
Christine F
CF
Conover
Julie R
JR
Miller
Alexander
A
Balaez
Sarah M
SM
Combs
Alicia M
AM
Leeper
Alyssa A
AA
Williams
Stephanie A
SA
Lachacz
Nigel
N
Zheng
Thomas J
TJ
Wronski
Stephen E
SE
Borst
D045930:Anabolic Agents / Q000494:pharmacology; D000077384:Anastrozole; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D006537:Heptanoates / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology*; D009919:Orchiectomy; D010024:Osteoporosis / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013739:Testosterone / Q000494:pharmacology*; D014204:Trenbolone Acetate / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology*
D045930:Anabolic Agents; D000728:Androgens; D047072:Aromatase Inhibitors; D006537:Heptanoates; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D013739:Testosterone; D001141:Aromatase; D014204:Trenbolone Acetate
HORMONE REPLACEMENT; MICROCOMPUTED TOMOGRAPHY; PRECLINICAL STUDIES; SEX STEROIDS; SKELETAL MUSCLE