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* Department of Morphology, Laboratory of Cellular Biology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, 31270-901 Brazil; and
Departments of Pharmacology and
Internal Medicine-Geriatrics Research, Southern Illinois University School of Medicine, Springfield, Illinois 62794
To whom requests for reprints should be addressed at 1 Laboratory of Cellular Biology, Avenue Antonio Carlos 6627, Pampulha Belo Horizonte, MG 31270-901, Brazil. E-mail: jsrocha21{at}bio-cel.dout.ufmg.br
The hypothalamic-pituitary-gonadal (HPG) axis and the somatotropic axis are influenced by nutritional factors. Calorie restriction (CR) extends lifespan but suppresses both the HPG and the somatotropic axes. Since most CR studies use a fairly severe (40%–60%) reduction of calorie intake, we hypothesized that a milder CR (20%) might not be deleterious to reproduction in male mice. To test this hypothesis, we evaluated the effects of 20% CR on testicular testosterone content and on testicular expression of genes that are relevant to testicular function and reproductive competence, including insulin-like growth factor-I, cytochrome P450 aromatase (Cyp19a1), androgen receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor, cytochrome P450c17 and 3-ß-hydroxysteroid dehydrogenase/isomerase. To relate CR effects to the activity of the somatotropic axis, we have used growth hormone–resistant GHR knockout mice as well as transgenic mice overexpressing GH. Mild CR did not affect testosterone levels in testis homogenates and had little effect on expression of the examined genes in the reproductive organs. Altered activity of the GH/insulin-like growth factor–1 axis had a major impact on the parameters analyzed. The results also suggest that expression of several key genes involved in the control of testicular function is preserved under conditions of mild CR and encourage speculation that mild regimens of CR can produce longevity benefits without impairing reproduction.
Key Words: calorie restriction testicular testosterone levels steroidogenesis-related genes growth hormone mutant mice
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