Most adult female mammals are reproductively active and give birth once or multiple times. Surprisingly, little attention, however, has been given to the possible long-term effects of prior reproductive experience on neural functions and the impact of possible changes in parity associated neuro endocrine functions on pituitary function in spite of the fact that parous women display reduced circulating titers of androgens and prolactin years after giving birth. In preliminary studies in the rat, we have found similar reductions in prolactin secretion in reproductively experienced females during subsequent pregnancies and lactations as well as reductions in neural sensitivity to opioid peptides, known regulators of prolactin. The present proposal draws upon these findings and examines the effects of parity on prolactin secretion and its possible regulators. An initial series of studies will delineate the conditions under which past reproductive experience alters prolactin secretion and pituitary prolactin content (measured by RIA) and message during subsequent pregnancies, lactations, and estrous cycles. The persistence (duration) and breadth (effects on other pituitary hormones, i.e. LH) of the neuroendocrine changes produced by a prior parity will also be assessed. We will then examine whether and to what extent prior parity alters neural dopaminergic and opioidergic systems, systems that inhibit and stimulate prolactin secretion, respectively. Tyrosine hydroxylase activity in neural tissues will be measured by HPLC and the endocrine responses of females to dopamine antagonists and opioid agonists will be determined. Possible parity-associated increases in CNS sensitivity to prolactin (autofeedback) and changes in sensory processing will be examined to evaluate whether these neural systems contribute to the parity-associated alterations in prolactin release. A final experiment will determine which components of a prior reproductive experience, i.e. pregnancy/lactation, bring about these changes in neural function and pituitary hormone release. Overall, these studies will identify underlying mechanisms which contribute to the alterations in neural and endocrine functions produced by a previous parity in the adult female. Moreover, these studies will tell us how the brain and endocrine system change as a result of normal reproductive events in the adult mammal. The impact of these changes may extend to a wide variety of biological processes, including the prolongation of the reproductive lifespan of the female, immune function, and behavioral processes regulated by dopaminergic, opioidergic, and lactogenic systems.
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