Prolactin gene disruption does not compromise differentiation of tuberoinfundibular dopaminergic neurons.
Prolactin gene disruption does not compromise differentiation of tuberoinfundibular dopaminergic neurons.
复制标题
催乳素基因破坏不会损害结节漏斗部多巴胺能神经元的分化。
DOI：
10.1159/000054565
复制
发表时间：
2000
影响因子：
4.1
通讯作者：
Horseman,ND
中科院分区：
文献类型：
--
作者：
Phelps,CJ;Horseman,ND
在转录因子Prop-1或Pit-1自发突变的小鼠中，垂体不能产生催乳素（PRL）、GH和TSH，下丘脑调节PRL的多巴胺能（DA）神经元（A12区）数量减少50%以上。在这些突变体中，通过对新生儿进行PRL治疗可以维持正常的神经元群，但对成人则不然。靶向破坏小鼠PRL结构基因提供了一种分离PRL缺乏症的新模型，以检验PRL神经营养效应的特异性。本研究采用形态学方法评估了这些小鼠的垂体性结节基底多巴胺能（TIDA）神经元，并假设分离PRL缺乏也会导致TIDA神经元数量减少。采用甲醛诱导的内源性儿茶酚胺荧光和酪氨酸羟化酶（TH）免疫细胞化学方法对雌性和雄性纯合子prl缺失（- / -）小鼠和正常杂合子（+/ -）兄弟姐妹的大脑进行比较。计算机图像分析定量免疫染色强度，计数间脑DA三个脑区th免疫反应神经元总数。- / -小鼠A12核周和中隆起（ME） DA荧光强度降低；其他脑区的荧光与-和+/ -小鼠相似。A12核周- / -组TH免疫染色强度显著低于正常小鼠（p= 0.0001），但A13非垂体区（内侧无绒带）细胞体中TH免疫染色强度无显著差异。在体外ME中，PRL-null小鼠的TH免疫染色强度低于正常小鼠（p= 0.0001）。在雌性和雄性- / -小鼠中，核周和ME的TH强度均显著降低。然而，prl缺失小鼠的A12神经元数量并不低于正常的兄弟姐妹。+/和- / -小鼠在A13区和脑室周围A14区的th免疫反应细胞数量也无差异。prl缺失小鼠中存在A12 DA神经元的正常补体，尽管DA和TH大大减少，强调单个神经元的稳态含量和表型分化是非常不同的评估。结果表明，虽然缺乏刺激的PRL反馈信号会导致TIDA神经元活性降低，但这些细胞的分化并未受到不利影响。
In mice with spontaneous mutations in transcription factors Prop-1 or Pit-1, the pituitary fails to produce prolactin (PRL), GH and TSH, and numbers of hypothalamic PRL-regulating dopaminergic (DA) neurons (area A12) are reduced by more than 50%. A normal neuronal population can be maintained in these mutants by PRL treatment of neonates, but not of adults. Targeted disruption of the PRL structural gene in mice provides a new model of isolated PRL deficiency to test the specificity of the PRL neurotrophic effect. The present study used morphological methods to assess hypophysiotropic tuberoinfundibular dopaminergic (TIDA) neurons in these mice, with the hypothesis that isolated PRL deficiency also would lead to reduction in TIDA neuron number. Brains of female and male homozygous PRL-null (–/–) mice and normal heterozygous (+/–) siblings were compared using formaldehyde-induced endogenous catecholamine fluorescence and tyrosine hydroxylase (TH) immunocytochemistry. Immunostaining intensity was quantified using computerized image analysis, and total numbers of TH-immunoreactive neurons were counted in three diencephalic DA brain regions. Intensity of DA fluorescence in A12 perikarya and median eminence (ME) was reduced in–/–mice; fluorescence in other brain areas was comparable for–/–and+/–mice. Immunostaining intensity of TH was significantly lower (p= 0.0001) in–/–than in normal mice in perikarya of A12, but not in cell bodies of nonhypophysiotropic area A13 (medial zona incerta). In external ME, TH immunostaining intensity was lower (p= 0.0001) in PRL-null than in normal mice. The decrease in TH intensity in both perikarya and in ME was significant for both female and male–/–mice. However, numbers of A12 neurons in the PRL-null mice were not lower than those of normal siblings. TH-immunoreactive cell number also did not differ between+/–and–/–mice in areas A13 and periventricular A14. The presence of a normal complement of A12 DA neurons in the PRL-null mice, despite greatly reduced DA and TH, emphasizes that steady-state content and differentiation of phenotype in individual neurons are very different assessments. The results suggest that, although absence of the stimulatory PRL feedback signal results in diminished activity of TIDA neurons, differentiation of these cells is not adversely affected.