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Pregnant rats were treated with 30 mg metopirone (M) each day for 2 days and autopsied on the third day in various gestational periods (Days 18-20, 19-21, and 20-22). Control rats were treated with saline alone (S). The adrenals of intact fetuses in M-treated dams were significantly heavier than those of intact fetuses in S-treated dams in every experimental period. In both M- and S-treated dams, the adrenals of encephalectomized (E) fetuses were lighter than those of intact littermates. However, in the experimental period of Days 18-20 and 19-21, the adrenals of E fetuses in M-treated dams were slightly but significantly heavier than those of similar E fetuses in S-treated dams. In contrast, in the experimental period Days 20-22, there was no significant difference in the weight of adrenals of E fetuses of M- and S-treated dams. These changes in fetal adrenal weight were reflected histologically in parallel changes in the size of adrenocortical cells. The observations suggest that the fetal adrenal hypertrophy following maternal treatment with metopirone can occur to some extent independent of the fetal brain, but that close to the end of gestation the hypertrophy occurs completely under the control of the fetal brain.

SummaryIn our experiments, both ponderal and histologic observations on the adrenal support the view that in the rat the hypophysisadrenal axis begins to function before birth. After birth, there is an hiatus of 3 days during which the function is significantly reduced.

SummaryA fetal rat given epinephrine showed a depletion of the ascorbic acid in the adrenals, but a decapitated fetus did not, nor did an intact (nondecapitated) fetus given saline instead of epinephrine. In a premature newborn obtained by Caesarean section (detached from placenta or not detached), injection of epinephrine did not cause a depletion of the ascorbic acid. These observations support the views that in the rat the hypothalamic-hypophyseal adrenal axis begins to function before birth and that after delivery this axis temporarily becomes refractory to stimulation by injected epinephrine.