Characterization of New Members of the Steroid Receptor Super-Family

Abstract

SummaryWe have isolated and characterized new members of the steroid receptor super-family. The cDNA of one member, called TR2 receptor, was isolated from a human testis λgt11 cDNA library utilizing the homology of oligonucleotide probes to the DNA-binding domain common to members of the steroid receptor super-family. Expression of TR2 receptor cDNA produced a 52 kd DNA-binding protein that did not bind significantly to any known steroids. Based on Northern blot analysis, TR2 receptor mRNA is 2.5 kb in length and is relatively abundant in androgen-sensitive organs such as ventral prostate. Dot blot hybridization analysis showed that TR2 receptor mRNA levels increased after castration of rats. The increase was reversed by 5α-dihydrotestosterone injection, suggesting that the levels of TR2 receptor mRNA are negatively controlled by androgen in the rat ventral prostate. The cDNA of another member, called TR3 receptor was isolated from a human prostate λgt11 cDNA library. Nucleotide sequences showed that TR3 receptor may be closely related to NUR/77, the cDNA for which was isolated from a mouse fibroblast λgt10 cDNA library as one in a set of genes whose expression is rapidly activated by serum growth factors. Sequence analysis showed that NUR/77 cDNA contained two regions of sequence homology which correspond to the DNA- and hormone-binding domains of the steroid receptor super-family. Expression of NUR/ 77 mRNA yielded two detectable proteins with molecular weights of 64 kd and 58 kd.