Gender-dependent hypoxic tolerance mediated via gender-specific mechanisms

Abstract

Primary hypoxic tolerance and preconditioning are gender dependent and modulated in females during the estrus cycle. The underlying mechanisms, however, remain to be determined. mRNA of estrogen receptor-alpha (EAR), progesterone receptor (PR), and adenosine receptor subtypes A1 and A3 (A1R and A3R) were investigated with reverse transcriptase-PCR in hippocampi from control male and female mice and animals treated in vivo with a single i.p. injection of 20 mg/kg body weight 3-nitropropionate (3NP) 1 or 24 hr prior to preparation. Results were analyzed relative to expression in hippocampi from untreated males. mRNA levels of EAR and A1R were alike in males and females and unaltered by preconditioning with 3NP. In contrast, PR mRNA levels were alike in males and females during proestrus but lower during estrus and diestrus (85% +/- 15%, P < 0.05; and 80% +/- 10%, P < 0.05, respectively). Upon preconditioning, PR mRNA decreased to 67% +/- 19% (P < 0.05) and 56% +/- 13% (P < 0.05) during proestrus and diestrus, respectively, but was unaltered during estrus and in males. On preconditioning, A3R mRNA decreased from 115% +/- 16% to 86% +/- 29% (P < 0.05) during diestrus but remained at the control level during proestrus and estrus. With low-level expression of PRs, as achieved upon preconditioning, hypoxic tolerance is increased. Other than in males, adenosine A3 receptors are not up-regulated upon preconditioning in females. Thus, not only is net hypoxic tolerance gender dependent but mechanisms conferring hypoxic tolerance are gender specific.