Walker Ameae M
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
Mol Cell Endocrinol. 2007 Sep 30;276(1-2):1-9. doi: 10.1016/j.mce.2007.06.001. Epub 2007 Jun 28.
The aims of this review are three-fold: first, to collate what is known about the production and activities of phosphorylated prolactin (PRL), the latter largely, but not exclusively, as illustrated through the use of the molecular mimic, S179D PRL; second, to apply this and related knowledge to produce an updated model of prolactin-receptor interactions that may apply to other members of this cytokine super-family; and third, to promote a shift in the current paradigm for the development of clinically important growth antagonists. This third aim explains the title since, based on results with S179D PRL, it is proposed that agents which signal to antagonistic ends may be better therapeutics than pure antagonists-hence antagonistic agony. Since S179D PRL is not a pure antagonist, we have proposed the term selective prolactin receptor modulator (SPeRM) for this and like molecules.
第一，整理关于磷酸化催乳素（PRL）的产生和活性的已知信息，后者主要（但非唯一）通过使用分子模拟物S179D PRL来说明；第二，应用这些及相关知识来生成一个更新的催乳素-受体相互作用模型，该模型可能适用于这个细胞因子超家族的其他成员；第三，推动当前临床上重要生长拮抗剂开发范式的转变。这第三个目的解释了本文标题，因为基于S179D PRL的结果，有人提出向拮抗端发出信号的药物可能比纯拮抗剂更具治疗效果——因此是拮抗激动。由于S179D PRL不是纯拮抗剂，我们为此类分子提出了选择性催乳素受体调节剂（SPeRM）这一术语。
