Catecholamine secretion from the adrenal medulla of the fetus, regulation by hormones

In the ovine fetus, the adrenal medulla actively secretes catecholamines into the circulation under normal and stress conditions. Little is known regarding the endocrine regulation of adrenal medullary catecholamines secretion in the fetus. The present study was undertaken to investigate the direct effects of the hormones prolactin, angiotensin II and cortisol on catecholamine release from fetal adrenal medulla, and to determine whether the effect of the hormones change during development into adulthood. Adrenal medulla from fetal, newborn and adult pregnant sheep was collected, dispersed into single cells and plated. Following preincubation, the cells were treated with ovine prolactin or angiotensin II at 8, 40 and 200 μg/ml; or cortisol at 10^-8, 10^-7 and 10^-6 M for 24 h. Catecholamine release into the medium was measured at 3, 6, 12 and 24 h. Ovine prolactin at 8 to 200 μg/ml significantly stimulated the release of total catecholamines after 12 h of incubation. The effect of prolactin was dose-dependent such that the magnitude of the response increased and the response time shortened with increasing concentrations of prolactin. In addition, the release of all three catecholamines - dopamine, norepinephrine and epinephrine - was significantly elevated. In newborn cells, only the highest concentration of 200 μg/ml ovine prolactin stimulated total catecholamine release at 6 h and 12 h, with significant increases of the three catecholamines at 12 h. In maternal cells, stimulation of catecholamine release was observed also with the highest concentration of prolactin tested (200 μg/ml) and after 12 h of incubation, when only the release of epinephrine was significantly enhanced by 324%. Angiotensin II at 40 and 200 μg/ml stimulated the release of norepinephrine and epinephrine significantly at 24 h of incubation in fetal cells. Newborn and maternal cells showed no consistent response to angiotensin II during the 24 h period. Cortisol at 10^-7 and 10^-6 M enhanced the release of epinephrine alone from fetal cells at 24 h of incubation. Newborn and maternal cells did not respond to cortisol treatment. In summary, the results showed that ovine fetal adrenomedullary cells in culture can respond to prolactin, angiotensin II and cortisol by increasing the release of catecholamines. Under these in vitro conditions, the fetal cells appear more sensitive to the hormones than newborn and maternal cells. Since the concentrations of prolactin and angiotensin II required to elicit an effect of fetal cells in vitro exceed those found in normal intact fetuses, it is uncertain whether these two hormones would normally function as physiologic regulators of adrenal medullary secretion. In the case of cortisol, the in vitro effective concentration is within the physiologic range of cortisol found in the intact fetus, suggesting that cortisol may play a role in regulating adrenal medullary catecholamine secretion in the ovine fetus.