The objective of this proposal is to directly, actively immunize the baboon fetus against adrenocorticotropic hormone (ACTH) and to determine the effect of immunoneutralization of ACTH on both fetal adrenocortical function (dehydroepiandrosterone sulfate [DHEAS] and cortisol synthesis) and the length of gestation. The primate fetal adrenal cortex is the essential source of androgen for placental aromatization to estrogen. Estrogen production is integral in regulating the molecular and biophysical cascaded that leads to birth in primates. Despite the importance of the primate fetal adrenal as the source of androgen precursor for estrogen formation, the role of the primate fetus in the process of parturition remains unresolved. We propose to actively immunize fetal baboons against ACTH, the major peptide regulating cortisol and DHEA production in the primate fetus. Active immunization has been employed as a technique for examining the role of endogenous peptide and protein hormones in adults of various species. Immunization of the baboon fetus in utero provides an elegant approach to critically examine the role of the fetal hypothalamo- pituitary adrenal axis in initiating the events of normal term labor and delivery in a primate. This proposal brings together investigators with expertise in the endocrinology and biology of parturition, immunology of non human primates, and maternal fetal medicine to advance the use of active immunization of the primate fetus to directly address a critical question, namely, what is the role of fetal ACTH in regulating adrenocortical development related to parturition in a non-human primate? While advances have been made in the treatment and survival rate of preterm infants, the prevalence of preterm birth (approximately 9-10 percent) has not declined in the United States, Canada or other developed countries. Premature birth continues to be a major cause of infant mortality and is associated with increased risk o f neurological and other deficits. Identifying mechanisms that initiate the onset of normal term labor and delivery will lead to the development of better strategies for preventing premature birth.
