Serum and adrenal corticosterone was measured by competitive protein-binding radioassay in rats subjected to saline injection, ACTH administration or ether fumes. Groups of rats were tested at 5, 7, 9, 11, 13, 15, 20 and 25 days of age and measurement of hormone level was made either before treatment, to obtain basal values, or 15 min after treatment. Furthermore, the time-course of corticosterone release after ether was determined in 9- and 15-day-old rats. Neonatal rats responded to ether exposure, ACTH administration or saline injection with a significant rise in serum and adrenal corticosterone concentration above basal levels as early as 5 days of age. By 9 days of age, response to stress was qualitatively the same as that of the 25-day-old rat. The time course of adrenal responsiveness to ether stress was similar in 9- and 15-day-old rats, both age groups showing significant increases in hormone concentration by 15 min. These results contradict the concept of the ‘stress non-responsive period’ which was promoted by previous studies based on the nuorometric analysis of corticosterone.

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Previous reports suggested that the rat placenta had a rather limited capacity for steroidogenesis, particularly with respect to progesterone production. We found that the basal zone in the rat placenta, which contains the steroidogenic giant cells, can be isolated by simple surgical separation, and using them for in vitro incubations, significant conversion of pregnenolone-7 alpha-3H to progesterone-1H could be demonstrated. The 5alpha-reduced metabolites of progesterone, as well as compounds of the delta4 pathway, including 17alpha-hydroxyprogesterone, androstenedione and testosterone were also isolated and characterized. When progesterone-7alpha-3H was added as precursor, most of it remained unmetabolized, but qualitatively identical products were isolated as were found when pregnenolong-7alpha-3H was used as precursor. Incubations of the whole placenta and of labyrinth tissue yielded relatively much lower progesterone-3H from pregnenolone-7alpha-3H. Our results have thus established that the rat placenta is a steroidogenic organ, just as in many other species. Past difficulties in isolating progesterone from in vitro studies may possibly be due to the intense activity of the enzyme 5alpha-reductase when the whole placenta was used.