Abstract：
The neuroendocrine marker genes Ptprn and Ptprn2 encode protein tyrosine phosphatase receptors N and N2, two members of protein tyrosine phosphatase receptors void of enzymatic activity, and whose function and mechanism of action have not been elucidated. To explore the role(s) of Ptprn and Ptprn2 on the hypothalamic-pituitary-adrenal axis, we used mice in which both genes were knocked out (DKO). The focus in study was on corticotrophs and melanotrophs from the anterior and intermediate lobes of the pituitary gland, respectively. In both sexes, DKO caused an increase in the expression of the corticotroph/melanotroph genes Pomc and Tbx19 and the melanotroph-specific gene Pax7. We also found in vivo and in vitro increased synthesis and release of beta-endorphin, alpha-MSH, and ACTH in DKO mice, which was associated with increased serum corticosterone levels and adrenal mass. DKO also increased the expression of other melanotroph-specific genes, but not corticotroph-specific genes. The dopaminergic pathway in the hypothalamus and dopaminergic receptors in melanotrophs were not affected in DKO mice. However, hyperplasia of the intermediate lobe was observed in DKO females and males, accompanied by increased POMC immunoreactivity per cell. These results indicate that PTPRNs contribute to hypothalamic-pituitary-adrenal function by being involved in processes governing postnatal melanotroph development and Pomc expression.
摘要：
神经内分泌标记基因Ptprn和Ptprn2编码蛋白酪氨酸磷酸酶受体N和N2，蛋白酪氨酸磷酸酶受体的两个成员没有酶活性，其功能和作用机制尚未阐明。探讨Ptprn和Ptprn2对下丘脑-垂体-肾上腺轴的作用,我们使用了两个基因都被敲除的小鼠（DKO）。研究的重点是来自脑垂体前叶和中叶的皮质营养因子和黑素营养因子，分别。在两性中，DKO引起促肾上腺皮质激素/黑色素营养基因Pomc和Tbx19以及黑色素营养特异性基因Pax7的表达增加。我们还发现在体内和体外增加β-内啡肽的合成和释放，阿尔法-MSH,和ACTH在DKO小鼠中，这与血清皮质酮水平和肾上腺质量增加有关。DKO还增加了其他黑色素特异性基因的表达，但不是促肾上腺皮质激素特异性基因.在DKO小鼠中，下丘脑中的多巴胺能途径和黑养动物中的多巴胺能受体没有受到影响。然而,在DKO女性和男性中观察到中间叶增生，伴随着每个细胞POMC免疫反应性的增加。这些结果表明，PTPRN通过参与控制出生后黑色素营养发育和Pomc表达的过程来促进下丘脑-垂体-肾上腺功能。
