THYROXINE AND PROLACTIN EFFECT TIDA NEURON ACTIVITY

多巴胺（DA）水平、儿茶酚胺组织荧光和DA生物合成 在Snell正中隆起（ME）上有明显和选择性的缺陷 和艾姆斯侏儒鼠。 儿茶酚胺，可能是DA，在 在艾姆斯侏儒小鼠中，内侧基底下丘脑（MBH）也有缺陷。 这些动物的侏儒症是继发于缺乏生长激素（GH） 和甲状腺功能减退。 此外，这些侏儒小鼠似乎没有 循环催乳素（PRL）。 最近的数据表明， 2周可增强艾姆斯侏儒型ME的DA合成， 正常水平。 有趣的是，生长激素或甲状腺素（T4）替代治疗 有效的催乳素在增加儿茶酚胺的生物合成在侏儒 MBH。 总的来说，这些观察结果导致了我们的假设， 在出生后的成熟过程中具有关键的和以前未被怀疑的作用， 结节漏斗多巴胺（TIDA）神经元通路。 神经 该通路的末端负责正常高水平的 DA在ME中发现。神经化学，重组DNA和 形态学技术将用于确定（1）是否存在 TIDA细胞体缺乏（2）如果PRL诱导DA恢复 ME中的合成需要合成新的酪氨酸mRNA 羟化酶（TH），DA合成的限速酶，（3）如果GH或T4 具有增强DA合成的有效但相对延迟的作用， （4）TIDA神经元的生后发育 在正常小鼠中，可被实验诱导的低催乳素血症破坏 或甲状腺功能减退。 TIDA神经元通路被公认为是主要的机制 参与调节垂体前叶的PRL分泌。 的 获得的结果应该提供一个新的洞察到一个独特的和以前的 PRL的未被怀疑的作用，反过来，可能对出生后的发展， TIDA神经元通路。 从更广泛的意义上说，这些结果应该提供新的 关于前叶激素一般如何在大脑中起作用的信息， 组织和发展的下丘脑机制，调节 它们在成人中的分泌以及这些机制的成熟如何可能 会因产后循环激素不足而受到干扰。

Dopamine (DA) levels, catecholamine histofluorescence and DA biosynthesis are markedly and selectively deficient in the median eminence (ME) of Snell and Ames dwarf mice. Catecholamine, possibly DA, biosynthesis in the mediobasal hypothalamus (MBH) is also deficient in the Ames dwarf mouse. Dwarfism in these animals is secondary to an absence of growth hormone (GH) and hypothyroidism. Further, these dwarf mice appear to have no circulating prolactin (PRL). Recent data suggests that PRL replacement for 2 weeks enhances DA synthesis in the Ames dwarf ME although not to the normal level. Interestingly, GH or thyroxine (T4) replacement was as effective as PRL in increasing catecholamine biosynthesis in the dwarf MBH. Collectively, these observations have led to our hypothesis that PRL has a critical and previously unsuspected role in the postnatal maturation of the tuberoinfundibular dopamine (TIDA) neuronal pathway. The nerve terminals of this pathway are responsible for the normally high levels of DA found in the ME. A combination of neurochemical, recombinant DNA and morphologic techniques will be utilized to determine (1) if there is a deficiency of TIDA cell bodies (2) if the PRL induced restoration of DA synthesis in the ME requires the synthesis of new mRNA for tyrosine hydroxylase (TH), the rate limiting enzyme in DA synthesis, (3) if GH or T4 have potent although comparatively delayed effects to enhance DA synthesis in the dwarf ME, (4) whether the postnatal development of the TIDA neurons in normal mice can be disrupted by experimentally induced hypoprolactinemia or hypothyroidism. The TIDA neuronal pathway is well recognized as the primary mechanism involved in regulating PRL secretion by the anterior pituitary. The results obtained should provide a new insight into a unique and previously unsuspected role PRL, in turn, may have on the postnatal development of the TIDA neuron pathway. In more general terms, the results should provide new information as to how the anterior hormones in general may act in the organization and development of the hypothalamic mechanisms which regulate their secretion in the adult and how the maturation of these mechanisms may be disrupted by postnatal deficiencies in circulating hormones.