Effect of thiouracil-induced hypothyroidism on time course of adrenal response in 15 day old rats

Previous investigations have supported the suggestion that perinatal induction of hypothyroidism, using the goitrogen thiouracil, completely prevents elevation of circulating corticosterone levels 15 min after ether stress in 15 day old rats. The present study used radioimmunoassay (RIA) to evaluate the effect of chemical hypothyroidism on response of circulating corticosterone to ether stress, or to exogenous corticotropin releasing factor (CRF), at 15, 30, or 45 min after stimulation. Fifteen day old hypothyroid rat pups responded to ether stress with a linear increase in circulating corticosterone over the time course of the study, and with the levels at 30 and 45 min significantly greater than unstimulated. However, the slope of the increase was markedly subnormal, as was corticosterone level at each time point after stress. On the other hand, CRF injection resulted in elevations of corticosterone along the time course that were similar for normal and thiouracil exposed rats. The results of this study do not support the previous conclusion that chemical hypothyroidism entirely abolishes adrenal axis response in 15 day old rats. Instead, thiouracil depresses the response at a number of post-stimulation time points, rather than causing a time-dependent delay in a normal corticosterone elevation. This is likely the result of thiouracil-induced functional deficits in all components of the neuroendocrine axis regulating corticosterone secretion, with particularly severe effects at the hypothalamus.