Departments of Pharmacology and Physiology and Biophysics, University of Tennessee, Memphis, College of Medicine, Memphis, Tennessee 38163, USA.
J Neuroendocrinol. 1990 Feb 1;2(1):19-24. doi: 10.1111/j.1365-2826.1990.tb00387.x.
Abstract Previous results from this laboratory indicate that female rats who consume milk deficient in prolactin (PRL) during the neonatal period subsequently display hyperprolactinemia, associated with decreased activity in the tubero-infundibular dopamine (DA) system and decreased lactotrope responsiveness to DA receptor stimulation. The present studies tested whether these neuroendocrine consequences of neonatal PRL deficiency can be mimicked by exposure of neonatal rats to estradiol. Female rats were injected sc with 1 mUg estradiol benzoate or oil vehicle on postpartum Days one to 3, while in other experiments, females were made neonatally deficient in PRL through treatment of their mothers with the DA agonist bromocriptine, a treatment that reduces the levels of PRL in milk. Females treated neonatally with estradiol benzoate, as well as offspring of the bromocriptine-treated mothers, displayed hyperprolactinemia as young adults, as compared to their respective vehicle-matched controls, and in both cases, this was abolished by ovariectomy, indicating dependence upon ovarian secretions. As reported previously in neonatal PRL-deficient females, neonatal estradiol benzoate-treated animals also exhibited reduced steady state levels and decreased turnover rates of DA in the median eminence when 35 days of age. DA levels and turnover rates in this region were still significantly reduced on postpartum Day 60. The DA agonist bromocriptine suppressed PRL release to a similar extent in cultured anterior pituitary cells from neonatal estrogen-treated and control rats, suggesting normal responsiveness of DA receptors on lactotrope cells in both groups. The present results confirm the ability of estradiol treatment or induction of a PRL deficiency during the early neonatal period to induce subsequent hyperprolactinemia in female rats, and further indicate that the hyperprolactinemic conditions resulting from either neonatal manipulation are dependent on the ovary and are associated with decreased levels and turnover of DA in the median eminence during the prepubertal period. Although these findings suggest that increased exposure to estradiol during the neonatal period may underlie the similar effects of neonatal PRL deficiency, the further observations in neonatal estrogen-treated rats that 1) decreased DA turnover in the median eminence persists at Day 60, and 2) lactotrope responsiveness to DA is normal, differ from results obtained previously in PRL-deficient rats. Thus, enhanced exposure to estrogen during the neonatal period does not appear to account for all of the neuroendocrine consequences of neonatal PRL deficiency.
本实验室之前的研究结果表明，在新生期摄入缺乏催乳素（PRL）的牛奶的雌性大鼠随后会出现高催乳素血症，这与结节漏斗多巴胺（DA）系统活性降低以及催乳素细胞对 DA 受体刺激的反应性降低有关。本研究旨在测试新生期暴露于雌二醇是否可以模拟这种新生期 PRL 缺乏的神经内分泌后果。雌性大鼠在产后第 1 至 3 天每天通过 sc 注射 1 mUg 苯甲酸雌二醇或油载体，而在其他实验中，通过用 DA 激动剂溴隐亭处理其母亲来使雌性大鼠在新生期缺乏 PRL，这种处理会降低乳汁中的 PRL 水平。与各自的载体匹配对照组相比，用苯甲酸雌二醇处理的新生雌性大鼠以及溴隐亭处理的母亲的后代在成年早期都表现出高催乳素血症，并且在这两种情况下，卵巢切除术都消除了这种情况，表明其依赖于卵巢分泌物。正如之前在新生期 PRL 缺乏的雌性大鼠中报道的那样，新生期接受苯甲酸雌二醇处理的动物在 35 天时也表现出中脑内 DA 的稳态水平降低和周转率降低。在产后第 60 天，该区域的 DA 水平和周转率仍然显著降低。DA 激动剂溴隐亭对来自新生期接受雌激素处理和对照组大鼠的培养前叶细胞的 PRL 释放的抑制作用相似，表明两组的催乳素细胞上的 DA 受体反应正常。本研究结果证实了在新生期早期用雌二醇处理或诱导 PRL 缺乏都能诱导雌性大鼠随后出现高催乳素血症，并进一步表明，无论是哪种新生期操作导致的高催乳素血症状态都依赖于卵巢，并且与青春期前时期中脑内 DA 的水平和周转率降低有关。尽管这些发现表明，在新生期暴露于雌二醇的增加可能是新生期 PRL 缺乏的类似作用的基础，但在新生期接受雌二醇处理的大鼠中进一步观察到以下结果：1）中脑内 DA 周转率的降低在第 60 天仍持续存在，2）催乳素细胞对 DA 的反应正常，这与之前在 PRL 缺乏大鼠中获得的结果不同。因此，在新生期暴露于雌激素的增加似乎并不能解释新生期 PRL 缺乏的所有神经内分泌后果。
