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 endocrine and neural functions in adult females. The present proposal draws upon the finding that parity produces long-term alterations in circulating prolactin (PRL) and androgens in women, similar reductions in PRL secretion in reproductively experienced rats, and an increase in dopaminergic tone in both women and rats. The overall aim of this proposal is to characterize the extent and basis of the endocrine and neural changes induced by prior parity. The first series of studies will characterize the effects of parity on pituitary RL and estradiol secretion in parous and nulliparous female rats. The effects of parity on estrogen receptors and whether parity produces a reduction in estrogen feedback regulation on PRL will then be investigated. Next, the contribution of elevated PRL during lactation on its own secretion later in adulthood will be measured. The second series of experiments will determine how parity may increase dopaminergic function, an increase which may underlie the reductions in PRL secretion in parous animals. The effects of parity on dopamine receptors, second messengers that mediate dopamine action, and estrogenic regulation of dopamine release both in hypothalamic and extrahypothalamic areas (using an in vivo microdialysis system combined with HPLC) will be measured. The possible decrease in sensitivity of dopamine neurons to PRL regulation as a result of prior parity will then be evaluated. The third set of studies will examine whether the effects of parity on PRL secretion are age-dependent. The effects of the age of first parity on circulating estrogen levels late in adulthood and estrogen regulation of PRL secretion will be determined. Overall, these studies will identify underlying mechanisms which contribute to the alterations in endocrine and neural functions produced by a previous parity in the adult female, alterations which may affect a wide spectrum of biological processes, including behavior, reproductive fertility, immune function, and hormone secretion, over the life span of the female.
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