Kelly P A, Djiane J, Postel-Vinay M C, Edery M
Laboratory of Molecular Endocrinology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Endocr Rev. 1991 Aug;12(3):235-51. doi: 10.1210/edrv-12-3-235.
PRL and GH are hormones with a wide spectrum of actions. Specific receptors are widely distributed in a number of classical target organs, but other tissues that are not known targets also contain measurable binding sites or receptor mRNA. The most likely explanation is that PRL and GH cause effects that have not yet been characterized in certain tissues. Cloning of the cDNAs encoding PRL and GH receptors has led to the discovery that the receptors, like the hormones themselves, form a gene family. Multiple receptor forms have been identified, including a short form, which for PRL is a membrane-bound receptor or for GH is a soluble BP, and a long form, which for both PRL and GH is a membrane-bound receptor. PRL and GH receptors, and the mRNAs encoding them, can be up- and down-regulated. GH induces an up-regulation of both GH and PRL receptors, whereas PRL stimulates an increase of only its own receptor. High concentrations of either hormone induce a homologous down-regulation of receptor expression. An assay has been developed to measure the functional activity of different forms of PRL receptor by cotransfecting a milk protein fusion gene specific to PRL coupled to a reporter-gene along with the cDNA of the PRL receptor. Although the short form represents the major form present in rat mammary gland, only the long form of receptor is able to stimulate milk protein gene transcription. For GH, increased expression of the receptor in some target cells is accompanied by a modest enhancement of the response to GH. No single second messenger mediating the action of either PRL or GH has been identified. Several potential components of the signal transduction pathways have been identified, but as yet none has clearly been shown to be able to mimic the effect of PRL or GH. Because of the wide range of biological actions associated with PRL, and the existence of various forms of PRL receptors, it is doubtful that one unifying mechanism of action will be found for this hormone. No human or animal model of a genetic defect of the PRL receptor has thus far been published. Mutations in the GH receptor gene have been demonstrated in Laron type dwarfism. Different exon deletions or point or nonsense mutations resulting in modifications in the extracellular, GH binding region of the GH receptor have been reported.(ABSTRACT TRUNCATED AT 400 WORDS)
催乳素（PRL）和生长激素（GH）是具有广泛作用的激素。特异性受体广泛分布于许多经典靶器官中，但其他未知的靶组织也含有可测量的结合位点或受体信使核糖核酸（mRNA）。最可能的解释是，PRL和GH在某些组织中产生了尚未被描述的效应。编码PRL和GH受体的互补脱氧核糖核酸（cDNA）的克隆已导致发现这些受体与激素本身一样，形成了一个基因家族。已鉴定出多种受体形式，包括一种短形式，对于PRL而言是一种膜结合受体，对于GH而言是一种可溶性结合蛋白（BP），以及一种长形式，对于PRL和GH而言都是一种膜结合受体。PRL和GH受体以及编码它们的mRNA可以上调和下调。GH诱导GH和PRL受体的上调，而PRL仅刺激其自身受体的增加。两种激素的高浓度都会诱导受体表达的同源下调。已开发出一种检测方法，通过将与报告基因偶联的PRL特异性乳蛋白融合基因与PRL受体的cDNA共转染来测量不同形式PRL受体的功能活性。虽然短形式是大鼠乳腺中存在的主要形式，但只有长形式的受体能够刺激乳蛋白基因转录。对于GH，某些靶细胞中受体表达的增加伴随着对GH反应的适度增强。尚未确定介导PRL或GH作用的单一第二信使。已鉴定出信号转导途径的几个潜在成分，但到目前为止，还没有一个被明确证明能够模拟PRL或GH的作用。由于与PRL相关的广泛生物学作用以及各种形式PRL受体的存在，怀疑是否能找到这种激素的一种统一作用机制。迄今为止，尚未发表PRL受体基因缺陷的人类或动物模型。生长激素受体基因的突变已在拉伦型侏儒症中得到证实。已报道了不同的外显子缺失或点突变或无义突变，这些突变导致生长激素受体细胞外GH结合区域发生改变。（摘要截断于400字）
