ENDOCRINE CONTROL OF FETAL ADRENAL MEDULLA CATECHOLAMINE

点击翻译按钮获取中文摘要

The purpose of the proposed study is to investigate the role of selected hormones and the adrenal cortex in the regulation of adrenal medullary catecholamine secretion in the ovine fetus. To study the hormone effects, fetuses of 100-115 days, 120-135 days, and 135-145 days gestation, newborns at 1-5 days and 5-10 days, and the adult ewe will be studied. The adrenal medulla will be dispersed into single cells, plated and cultured in Krebs-Henseleit medium. The effects of prolactin, angiotensin II, arginine vasopressin and cortisol on the synthesis and release of the three catecholamines-dopamine, norepinephrine, and epinephrine-will be determined at 1, 3, 6, 9, 12 and 24 hours of incubation. A radioenzymatic assay will be used to measure the concentrations of the three catecholamines. Dose-response relationships will be established. The responsiveness of the adrenal medulla to each of the hormones will be compared among animals of different age groups. To study the role of the adrenal cortex in regulating medullary catecholamine secretion, the ability of the cortex to release a catecholamine stimulatory factor will be determined using adrenal tissues from fetuses of 135 to 140 days gestation. First, cortical cell incubation medium will be tested for catecholamine stimulatory activity in adrenal medullary cells. Second, the secretory pattern of this catecholamine stimulatory factor will be determined by testing the medium obtained from incubating adrenal cortical cells for periods up to 48 hours. Third, the augmentation of release of this catecholamine stimulatory factor from the cortical cells by ACTH and by the presence of adrenal medullary cells will be tested. For the latter study, fetal adrenal cortical cells will be recombined with medullary cells and coincubated. The release of the cortical factor will be correlated with morphologic changes or structural specialization as examined under the phase-contrast and electron microscope. Fourth, the isolation of this adrenal cortical catecholamine stimulatory factor will be performed using biochemical separation procedures. Finally, the presence of this cortical factor in the adrenal cortex of younger fetuses, newborns and adults will be investigated. These studies will provide the basic understanding of the endocrine factors involved in the regulation of adrenal medullary catecholamine secretion in the fetus during development. They will evaluate the significance of the role of the adrenal cortex in the control of adrenal medullary secretory function in the near-term fetus.