Castration prolongs tolerance of young male rats to pulmonary O2 toxicity.

We tested the hypothesis that the normal loss of tolerance of neonatal rats to prolonged hyperoxic exposure at around 1 mo of age might be related to the marked increase in sex hormones occurring around this period. Male rats castrated at 20 days of age demonstrated significantly increased survival in greater than 95% O2 compared with sham-operated rats when exposed to high O2 at various ages greater than 45 days [castrated, 115 of 166 (69%) vs. sham, 59 of 156 (38%) (P less than 0.001)]. Testosterone replacement led to survival rates comparable with sham-operated rats [30 of 87 (34%)]. No such protective effect was observed in female rats [survival: ovariectomy, 16 of 33 (48%) vs. sham, 14 of 28 (50%)]. The improved survival in the older castrated males was not associated with an increase in lung antioxidant enzymes, which is normally seen in O2-tolerant neonatal rats. Castration did result in marked morphological lung changes, including significantly enlarged lung volumes (4.54 +/- 0.72 vs. 3.76 +/- 0.29 ml/100 g) and terminal air spaces [mean linear intercept (LM) = 51.6 +/- 5.0 vs. 46.3 +/- 4.1 micron (P less than 0.001)]. Testosterone replacement also prevented these morphological changes. The altered lung growth 1) may be related to the influence of other endocrine imbalances after castration and 2) may be an important factor in the relative O2 tolerance of the castrated male rats beyond the neonatal period.