Effect of age and sex on plasma cortisol and dehydroepiandrosterone concentrations in the dog (Canis familiaris).

Limited data exist on age-related physiological variations in plasma concentrations of cortisol and dehydroepiandrosterone (DHEA) in dogs, despite their potential role in the pathophysiology of ageing. This study examined plasma cortisol and DHEA concentrations and cortisol/DHEA ratio variations, according to age and sex in 311 dogs, aged from two months to 16 years. Before adulthood, DHEA concentrations were higher in peri-pubertal males. During adulthood, cortisol and DHEA were higher in males than females. Among females, DHEA was lower in older dogs, but the decrease was observed at an older age in intact than ovariectomised females. Variations in the cortisol/DHEA ratio inversely reflected those of DHEA. Results indicate that testicles are an important source of DHEA in males, and that DHEA is mainly secreted by the adrenal glands in females. The ovaries' contribution to circulating DHEA appears to be limited, although it may partially compensate an age-related decrease in adrenal secretion.

Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility.

CONTEXT: Mutations in the androgen receptor (AR) gene can cause the androgen insensitivity syndrome (AIS). For complete and severe partial AIS, well-characterized in vitro functional assays can be used for genotype-phenotype correlation; however, for mild forms of AIS, as associated with male infertility, experimental evidence is scarce or lacking. In particular, optimal in vitro functional tests informative about the genotype-phenotype relation have not been described. OBJECTIVE: The objective of this study was to investigate the association among genotype and phenotype for AR mutations found in infertile males by conventional functional assays and additional in-depth studies performed with several gene reporters. DESIGN: To this aim, we selected four AR missense mutations associated with isolated male infertility (L547F and two novel mutations A474V and S650G) or partial AIS (Y571H). After introduction of the specific mutations in AR expression plasmid, we performed classical in vitro studies (Western immunoblotting, electrophoretic mobility shift assay, hormone-response curves) and transactivation assays with different reporter constructs (MMTV, Sc-ARU-TK, TAT-GRE- 2X, Slp-ARU-TK and PEM). RESULTS AND CONCLUSIONS: Our results showed that standard functional tests provide sufficient information only for severe AR mutations, whereas for AR mutations found in mild AIS patients with male infertility, only an extensive analysis with different in vitro systems, and in particular with PEM promoter, can give information on the functionality of the AR and therefore on the pathogenicity of the mutations and on genotype-phenotype correlation.