Dalton J T, Mukherjee A, Zhu Z, Kirkovsky L, Miller D D
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Biochem Biophys Res Commun. 1998 Mar 6;244(1):1-4. doi: 10.1006/bbrc.1998.8209.
Nonsteroidal androgens have not been reported. During studies to identify affinity ligands for the androgen receptor in our laboratory, we synthesized several electrophilic nonsteroidal ligands for the androgen receptor and examined their receptor binding affinity and ability to stimulate receptor-mediated transcriptional activation. We found that three of these ligands (1) bound the androgen receptor with affinity similar to that of dihydrotestosterone (the endogenous ligand) and (2) mimicked the effects of dihydrotestosterone on receptor-mediated transcriptional activation (i.e., they were receptor agonists). These studies demonstrate that nonsteroidal ligands can be structurally modified to produce agonist activity. These ligands thus represent the first members of a novel class of androgens with potential therapeutic applications in male fertility and hormone replacement therapy.
尚未有非甾体雄激素的相关报道。在我们实验室进行的旨在鉴定雄激素受体亲和配体的研究过程中，我们合成了几种用于雄激素受体的亲电非甾体配体，并检测了它们的受体结合亲和力以及刺激受体介导的转录激活的能力。我们发现其中三种配体：（1）与雄激素受体结合的亲和力与二氢睾酮（内源性配体）相似；（2）模拟了二氢睾酮对受体介导的转录激活的作用（即它们是受体激动剂）。这些研究表明，非甾体配体可以通过结构修饰产生激动剂活性。因此，这些配体代表了一类新型雄激素的首批成员，在男性生育和激素替代疗法中具有潜在的治疗应用价值。
