Shah G V, Shyr S W, Grosvenor C E, Crowley W R
Department of Physiology, University of Tennessee College of Medicine, Memphis 38163.
Endocrinology. 1988 May;122(5):1883-9. doi: 10.1210/endo-122-5-1883.
Previous findings from this laboratory suggest a role for milk-borne PRL in the development of the inhibitory neuroendocrine controls over PRL secretion. Thus, rats that consumed milk deficient in PRL on days 2-5 postpartum show reduced concentrations and turnover of DA in the median eminence and elevated serum levels of PRL at 30-35 days of age. The present experiments were undertaken to investigate whether these consequences of neonatal PRL deficiency persist beyond puberty, and whether alterations in pituitary responsiveness to hypothalamic hormones may be involved. Lactating rats received sc injections of either saline or the dopamine (DA) agonist bromocriptine (125 micrograms/rat.day) on each of days 2-5 postpartum, a treatment that reduces the amount of PRL in milk without abolishing lactation. Blood samples were obtained from male and female offspring at various postnatal ages, and PRL concentrations were determined by RIA. Serum PRL concentrations in offspring from both groups were low until after weaning, but the female offspring of bromocriptine-treated mothers showed significantly elevated serum PRL between days 30 and 90 postpartum. Male offspring of bromocriptine-treated mothers also had transiently increased serum PRL levels, which returned to control levels by day 40. The turnover rate of DA in the median eminence, calculated from the rate of decline after synthesis inhibition, was reduced on day 35 in neonatally PRL-deficient offspring, as shown previously. However, no differences in DA turnover between the two groups were apparent on day 60, indicating a recovery of normal dopaminergic activity. Anterior pituitary cells of 100-day-old control and neonatally PRL-deficient animals were dispersed, cultured for 3 days, and then exposed to either TRH, to stimulate PRL release, or to the DA agonist bromocriptine, which inhibits PRL release. Pituitary cells of neonatally PRL-deficient offspring were almost completely unresponsive to bromocriptine with regard to suppression of PRL release and cytoplasmic PRL mRNA levels. In contrast, pituitary cells of neonatal PRL-deficient offspring were somewhat more responsive to TRH in stimulating PRL release and increasing the levels of PRL mRNA. These results suggest that a brief period of PRL deficiency during the neonatal period may result in long-lasting alterations in control of PRL secretion. The resultant hyperprolactinemia may be initiated by a reduction in the release of DA from the hyothalamus, perhaps reflecting a role for milk-derived PRL in the functional development of this neurosecretory system, and maintained in part by a reduction in pituitary responsiveness to DA.
该实验室先前的研究结果表明，乳汁中的催乳素在催乳素分泌的抑制性神经内分泌控制的发育中起作用。因此，在产后第2 - 5天食用催乳素缺乏牛奶的大鼠，在30 - 35日龄时，其正中隆起中多巴胺（DA）的浓度和周转率降低，血清催乳素水平升高。本实验旨在研究新生儿催乳素缺乏的这些后果是否会持续到青春期之后，以及垂体对下丘脑激素的反应性改变是否与之有关。在产后第2 - 5天，给泌乳大鼠皮下注射生理盐水或多巴胺（DA）激动剂溴隐亭（125微克/大鼠·天），这种处理可减少乳汁中催乳素的量而不影响泌乳。在不同的出生后年龄从雄性和雌性后代采集血样，并用放射免疫分析法测定催乳素浓度。两组后代的血清催乳素浓度在断奶前都很低，但溴隐亭处理的母亲的雌性后代在产后30至90天血清催乳素显著升高。溴隐亭处理的母亲的雄性后代血清催乳素水平也有短暂升高，到第40天恢复到对照水平。如先前所示，从合成抑制后的下降速率计算得出，在出生时催乳素缺乏的后代中，正中隆起中DA的周转率在第35天降低。然而，在第60天，两组之间的DA周转率没有明显差异，表明多巴胺能活性恢复正常。将100日龄对照动物和出生时催乳素缺乏动物的垂体前叶细胞分散，培养3天，然后用促甲状腺激素释放激素（TRH）刺激催乳素释放，或用抑制催乳素释放的DA激动剂溴隐亭处理。出生时催乳素缺乏的后代的垂体细胞在抑制催乳素释放和细胞质催乳素mRNA水平方面对溴隐亭几乎完全无反应。相反，出生时催乳素缺乏的后代的垂体细胞在刺激催乳素释放和增加催乳素mRNA水平方面对TRH的反应性略高。这些结果表明，新生儿期短暂的催乳素缺乏可能导致催乳素分泌控制的长期改变。由此产生的高催乳素血症可能是由下丘脑DA释放减少引发的，这可能反映了乳汁来源的催乳素在这个神经分泌系统功能发育中的作用，并且部分是由垂体对DA的反应性降低维持的。
