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Cited by 88Hormonal and reproductive studiesAdrenal Hormones and DisordersBone health and osteoporosis research

An Aged Rat Model of Partial Androgen Deficiency: Prevention of Both Loss of Bone and Lean Body Mass by Low-Dose Androgen Replacement1

Vanderschueren, Dirk, Vandenput, Liesbeth, Boonen, Steven, Van Herck, Erik, Swinnen, Johannes V., Bouillon, Roger·2000·Endocrinology
DOI 10.1210/endo.141.5.7472
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Abstract

The aim of this study was to evaluate the effects of different doses of androgen replacement, both on body composition and bone, in an aged male orchidectomized rat model. Testosterone was administered by 0.5, 1, and 2.5-cm sc SILASTIC implants (release of, respectively, 11.5, 23, and 55 microg/day) to aged (12 months old, +/- 550 g) male orchidectomized Wistar rats during a 15-week experimental period. T 0.5 only partially prevented decrease of ventral prostate and seminal vesicle weight, compared with an intact group that received an empty implant (Intact). The 1-cm implant (T 1) completely prevented decrease of both seminal vesicles and ventral prostate weight. The 2.5-cm implant (T 2.5) was clearly supraphysiological, as demonstrated by significant hypertrophy of both androgen-sensitive organs. Serum testosterone was lower in T 0.5 and T 1 (0.38 +/- 0.06 ng/ml and 0.92 +/- 0.06 ng/ml, respectively) and higher in T 2.5 (2.4 +/- 0.28. ng/ml), compared with both Intact (1.6 +/- 0.23 ng/ml) and the baseline group(1.6 +/- 0.11 ng/ml). As expected, orchidectomized rats that received an empty SILASTIC implant had significantly lower bone mineral content (-7.9%), apparent density (-5.7%), and lean body mass (-10.8%), as measured by dual-energy x-ray absorptiometry, without significant changes in body weight and fat mass, compared with Intact. Also, cancellous (-50.3%) and cortical (-1.8%) volumetric density, as measured by peripheral quantitative computed tomography, were decreased in the tibia. Bone turnover, as measured by serum osteocalcin and urinary deoxypyridinoline excretion, was increased in orchidectomized rats that received an empty SILASTIC implant. T 0.5 prevented all changes, not only in bone mineral content, density, and turnover but also in lean body mass. Moreover, there were no significant differences, for all these parameters, between the different doses of testosterone replacement. In conclusion, low-dose androgen replacement does not lead to lower bone mineral density, higher bone turnover, and lower lean body mass in aged male rats, whereas complete androgen deficiency does. Therefore, the threshold concentration of testosterone necessary for prevention of both bone and lean body mass loss in aged male rats is clearly lower than for prostate and seminal vesicles.

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Authors
Vanderschueren, D., Vandenput, L., Boonen, S., Van Herck, E., Swinnen, J. V., & Bouillon, R.
Affiliations
KU Leuven (BE)
Corresponding author
Vanderschueren, Dirk
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2000-05
Volume
141
Issue
5
Pages
1642-1647
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endo.141.5.7472
OpenAlex
W2071620840
Cited by
88
References
24
Citations by year
2023: 3 · 2022: 3 · 2021: 5 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 9 · 2014: 4 · 2013: 2 · 2012: 4
FWCI
4.04
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • KU Leuven
  • Vlaamse regering
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
testosterone replacement therapy, aging, orchiectomy, bone mineral density, lean body mass, body composition, bone turnover, osteocalcin, deoxypyridinoline, seminal vesicle, ventral prostate, rat model
MeSH terms
Aging, Androgens, Animals, Body Composition, Bone Resorption, Disease Models, Animal, Male, Orchiectomy, Bone Density, Body Mass Index, Rats

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