The fetal hypothalamo-hypophyseal-adrenal axis (HHAA) is necessary for parturition and the maturation of the lung and other vital systems in sheep. However, available data do not prove that this axis triggers the processes of labor and delivery, only that it is necessary for the trigger to exert its effect. Using immunocytochemical techniques, we have shown that corticotropin-releasing factor (oCRF) is localized in the fetal paraventricular nucleus (PVN). Using stereotaxic lesions, we have shown that secretion of adrenocorticotropin (ACTH) is modified by PVN lesions.
Specific Aims : We will: I. examine histological development of oCRF-containing neurons in the fetal ovine hypothalamus. II. study both the fetal PVN's role and possible interactions of arginine vasopressin (AVP) and oCRF in regulating pulsatile secretion of fetal ACTH. III. study the effect of PVN lesions on glucocorticoid feedback following bilateral fetal adrenalectomy. IV. establish whether neurons in the fetal PVN regulate secretion of ACTH by the fetal pituitary gland in response to two clearly defined and controlled short-term stress stimuli - fetal hypoxemia and hypotension and determine if this regulatory activity is mediated by oCRF. We will use stereotaxic lesions of the PVN and a specific antagonist of oCRF and AVP to test our hypothesis that this regulatory activity is mediated by oCRF. We will also investigate AVP and oCRF interaction. V. investigate the hypothesis that neurons within the PVN are involved in the increased activity of the fetal HHAA that plays a central role in initiation of parturition. We hypothesize that this activity is mediated by oCRF. These studies are the logical continuation of systematic, controlled experiments to elucidate the regulation of increased fetal adrenal function that occurs before delivery in sheep and primates.
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