NEURAL AND ENDOCRINE CONSEQUENCES OF PARITY

大多数成年雌性哺乳动物都有生殖能力，生育一次或多次。令人惊讶的是，很少有人注意到，然而，以前的生殖经验对成年女性的内分泌和神经功能可能产生的长期影响。目前的建议借鉴的发现，奇偶产生长期的改变，循环催乳素（PRL）和雄激素的妇女，类似的减少PRL分泌的生殖经验丰富的大鼠，并增加多巴胺能紧张的妇女和大鼠。本提案的总体目标是描述先前产次引起的内分泌和神经变化的程度和基础。第一系列研究将描述产次对经产和未经产雌性大鼠垂体RL和雌二醇分泌的影响。然后将研究产次对雌激素受体的影响以及产次是否会减少雌激素对PRL的反馈调节。接下来，将测量泌乳期间升高的PRL对成年期后期自身分泌的贡献。第二个系列的实验将确定如何奇偶性可能会增加多巴胺能功能，增加这可能是减少PRL分泌的经产动物。将测量产次对多巴胺受体、介导多巴胺作用的第二信使以及下丘脑和下丘脑外区域中多巴胺释放的雌激素调节的影响（使用体内微透析系统结合HPLC）。然后将评估作为先前产次的结果的多巴胺神经元对PRL调节的敏感性的可能降低。第三组研究将检查产次对PRL分泌的影响是否具有年龄依赖性。首次产次年龄对成年晚期循环雌激素水平的影响以及雌激素对PRL分泌的调节将被确定。总体而言，这些研究将确定导致成年雌性先前产次产生的内分泌和神经功能改变的潜在机制，这些改变可能影响广泛的生物学过程，包括行为，生殖生育力，免疫功能和激素分泌，在雌性的整个生命周期内。

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.