PROLONGATION OF TOLERANCE TO PULMONARY O2 TOXICITY BY CASTRATION OF YOUNG MALE RATS

Abstract

Neonatal animals of several species are relatively resistant to pulmonary O2 toxicity. Young rats progressively lose their O2 tolerance after age 30 days, which is approximately the time of pubertal sex hormone surges. We therefore castrated male (CAST) and female (OVARX) rats at age 20 days and exposed them to hyperoxia at ages 45 to 80+ days to determine whether endocrine changes are important to age-related loss of O2 tolerance. Survival results (100% O2, 72 hrs):The findings that female castration had no protective effect against hyperoxia (survival at age 55 days: SHAM=14/28 vs. OVARX=16/33), and that TESTO replacement reversed the improved survival seen in CAST male rats at all ages tested, indicate an important role for TESTO in the loss of O2 tolerance. CAST (but not OVARX) was also associated with altered lung development, including increased lung volume (4.54±.72 vs. 3.76±.29ml/100gms for SHAM controls) (p<0.01) and morphometric evidence of significantly enlarged alveoli. The post-natal role of TESTO in lung development (and tolerance/susceptibility to O2 toxicity) is a potentially fertile new area for future study.