The tumor suppressor gene Reversion-inducing cysteine-rich protein with Kazal motifs (Reck) encodes a membrane-anchored protease regulator expressed in multiple tissues in mouse embryos and is essential for embryonic development. In postnatal mice, however, physiological roles for the RECK protein remain unclear. We found in this study that Reck is abundantly expressed in growth hormone (GH)-producing cells (somatotrophs) in the anterior pituitary gland (AP). We also found that two types of viable Reck mutant mice, one with reduced RECK expression (Hypo mice) and the other with induced Reck deficiency from 10 days after birth (iKO mice treated with tamoxifen), exhibit common phenotypes including decreases in body size and plasma levels of insulin-like growth factor-1 (IGF1). To gain insights into the function of RECK in the AP, we characterized several somatotroph-associated molecules in the AP of these mice. Immunoreactivity of GH was greatly reduced in tamoxifen-treated iKO mice; in these mice, two membrane receptors involved in the stimulation of GH secretion [growth hormone secretagogue receptor (GHSR) and growth hormone releasing hormone receptor (GHRHR)] were decreased, however, their mRNAs were increased. Decrease in GHSR immunoreactivity and concomitant increase in its mRNA were also found in the other mutant line, Hypo. Furthermore, reduced immunoreactivity of growth hormone receptor (GHR) and concomitant increase in its mRNA was also found in the liver of Hypo mice. These results raise the possibility that RECK supports proper functioning of the GH/IGF1 axis in mice, thereby affecting their growth and metabolism.

中文翻译：

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膜锚定的蛋白酶调节因子RECK在垂体前叶中的大量表达及其在小鼠生长激素/胰岛素样生长因子1轴中的意义。

具有Kazal基序（Reck）的肿瘤抑制基因逆转诱导型富含半胱氨酸的蛋白质编码在小鼠胚胎的多个组织中表达的膜锚定蛋白酶调节剂，对胚胎发育至关重要。然而，在产后小鼠中，RECK蛋白的生理作用仍不清楚。我们在这项研究中发现，Reck在垂体前叶（AP）的生长激素（GH）产生细胞（somatotrophs）中大量表达。我们还发现，两种类型的可行Reck突变小鼠，一种具有降低的RECK表达（Hypo小鼠），另一种具有自出生后10天起诱导的Reck缺乏（使用他莫昔芬治疗的iKO小鼠），表现出常见的表型，包括体型减小和血浆胰岛素样生长因子-1（IGF1）的水平。要深入了解RECK在AP中的功能，我们在这些小鼠的AP中表征了几种与营养营养相关的分子。他莫昔芬治疗的iKO小鼠中GH的免疫反应性大大降低；在这些小鼠中，参与GH分泌刺激的两种膜受体[生长激素促分泌素受体（GHSR）和生长激素释放激素受体（GHRHR）]减少，但是它们的mRNA增加。在另一突变株Hypo中也发现GHSR免疫反应性降低和其mRNA随之增加。此外，还发现在Hypo小鼠的肝脏中，生长激素受体（GHR）的免疫反应性降低，并且其mRNA随之增加。这些结果提高了RECK支持小鼠GH / IGF1轴正常运作的可能性，从而影响了它们的生长和代谢。