Dataset Information

Testosterone boosts physical activity in male mice via dopaminergic pathways.

ABSTRACT: Low testosterone (T) in men, especially its free fraction, has been associated with loss of energy. In accordance, orchidectomy (ORX) in rodents results in decreased physical activity. Still, the mechanisms through which T stimulates activity remain mostly obscure. Here, we studied voluntary wheel running behavior in three different mouse models of androgen deficiency: ORX, androgen receptor (AR) knock-out (ARKO) and sex hormone binding globulin (SHBG)-transgenic mice, a novel mouse model of "low free T". Our results clearly show a fast and dramatic action of T stimulating wheel running, which is not explained by its action on muscle, as evidenced by neuromuscular studies and in a muscle-specific conditional ARKO mouse model. The action of T occurs via its free fraction, as shown by the results in SHBG-transgenic mice, and it implies both androgenic and estrogenic pathways. Both gene expression and functional studies indicate that T modulates the in vivo sensitivity to dopamine (DA) agonists. Furthermore, the restoration of wheel running by T is inhibited by treatment with DA antagonists. These findings reveal that the free fraction of T, both via AR and indirectly through aromatization into estrogens, stimulates physical activity behavior in male mice by acting on central DA pathways.

SUBMITTER: Jardi F

PROVIDER: S-EPMC5772634 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Testosterone boosts physical activity in male mice via dopaminergic pathways.

Jardí Ferran F Laurent Michaël R MR Kim Nari N Khalil Rougin R De Bundel Dimitri D Van Eeckhaut Ann A Van Helleputte Lawrence L Deboel Ludo L Dubois Vanessa V Schollaert Dieter D Decallonne Brigitte B Carmeliet Geert G Van den Bosch Ludo L D'Hooge Rudi R Claessens Frank F Vanderschueren Dirk D

Scientific reports 20180117 1

Low testosterone (T) in men, especially its free fraction, has been associated with loss of energy. In accordance, orchidectomy (ORX) in rodents results in decreased physical activity. Still, the mechanisms through which T stimulates activity remain mostly obscure. Here, we studied voluntary wheel running behavior in three different mouse models of androgen deficiency: ORX, androgen receptor (AR) knock-out (ARKO) and sex hormone binding globulin (SHBG)-transgenic mice, a novel mouse model of "lo ...[more]

PMID: 29343749

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Project description:The gut bacteria of the family Christensenellaceae are consistently associated with metabolic health, but their role in promoting host health is not fully understood. Here, we explored the effect of Christensenella minuta amendment on voluntary physical activity and the gut microbiome. We inoculated male and female germ-free mice with an obese human donor microbiota together with live or heat-killed C. minuta for 28 days and measured physical activity in respirometry cages. Compared to heat-killed, the live-C. minuta treatment resulted in reduced feed efficiency and higher levels of physical activity, with significantly greater distance traveled for males and higher levels of small movements and resting metabolic rate in females. Sex-specific effects of C. minuta treatment may be in part attributable to different housing conditions for males and females. Amendment with live C. minuta boosted gut microbial biomass in both sexes, immobilizing dietary carbon in the microbiome, and mice with high levels of C. minuta lose more energy in stool. Live C. minuta also reduced within and between-host gut microbial diversity. Overall, our results showed that C. minuta acts as a keystone species: despite low relative abundance, it has a large impact on its ecosystem, from the microbiome to host energy homeostasis.IMPORTANCEThe composition of the human gut microbiome is associated with human health. Within the human gut microbiome, the relative abundance of the bacterial family Christensenellaceae has been shown to correlate with metabolic health and a lean body type. The mechanisms underpinning this effect remain unclear. Here, we show that live C. minuta influences host physical activity and metabolic energy expenditure, accompanied by changes in murine metabolism and the gut microbial community in a sex-dependent manner in comparison to heat-killed C. minuta. Importantly, live C. minuta boosts the biomass of the microbiome in the gut, and a higher level of C. minuta is associated with greater loss of energy in stool. These observations indicate that modulation of activity levels and changes to the microbiome are ways in which the Christensenellaceae can influence host energy homeostasis and health.

Project description:ObjectiveTo compare the effect of exogenous short-acting and long-acting testosterone on male reproductive potential in mice.DesignIn vivo mouse model.SettingUniversity-based basic science research laboratory.AnimalsA total of 30 wild-type C57BL/6 male and female mice were used for this experimentation. The male mice were used for control group and testosterone supplementation, while both male and female mice were used for the breeding portion of the study.InterventionsExogenous testosterone was administered either in short-acting formulation (Monday-Wednesday-Friday dosing schedule, testosterone propionate 0.2 mg/kg), or long-acting formulation (3-month dosing schedule - testosterone pellets 150 mg) to male mice.Main outcome measuresTime to pregnancy, Luteinizing hormone (LH) levels, and testicular weight.ResultsMice treated with long-acting testosterone appear to have longer time to pregnancy when compared to wild-type (33 ± 11 vs 23 ± 2.6 days, p ≤ 0.05) and mice that received short-acting testosterone propionate (26 ± 5.9 days). Mice treated with long-acting testosterone had smaller testes weight when compared to control (0.08 ± 0.01 vs 0.11 ± 0.01g; p ≤ 0.01), while the short-acting testosterone treated mice had similar testis weight when compared to control (0.09 ± 0.02 vs 0.11 ± 0.01g; ns). The serum testosterone level was elevated in mice that received testosterone pellets (285.78 ng/dL) and testosterone propionate (122.16 ng/dL) versus control (68.4 ng/dL). In mice that received long-acting testosterone pellets, LH levels at 3 months were almost undetectable while those that received short-acting testosterone remained similar to control (0.017 ± 0.058 vs 0.348 ± 0.232 IU/L; p ≤ 0.01). Female reproductive potential parameters including litter size and pup weight were collected and observed to have no difference between groups.ConclusionThrough a mouse breeding study, mice that received short-acting testosterone were shown to have fertility potential similar to wild-type male mice. Long-acting exogenous testosterone appeared to impair male reproductive capacity and LH levels when compared to short-acting testosterone. Short-acting testosterone appeared to cause less LH suppression. Identifying strategies to increase testosterone while simultaneously preserving male fertility is important for treating young men with hypogonadism.

Dataset Information

Testosterone boosts physical activity in male mice via dopaminergic pathways.

Publications

Testosterone boosts physical activity in male mice via dopaminergic pathways.

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