Expression and distribution of androgen-binding protein/sex hormone-binding globulin in the female rodent reproductive system.

Abstract

Androgen-binding protein (ABP)/sex hormone-binding globulin gene expression has been described in the rat testicular Sertoli cell and brain. The extracellular protein is thought to regulate the bioavailability of sex steroids, but may have a more complex function as a hormone or growth factor. Transgenic mice were developed with a 5.5-kilobase (kb) rat DNA fragment containing the ABP gene with all 8 exon sequences and 1.5 kb upstream of the transcription start site. Expression of the gene was observed in the testis and brain, but not in other examined tissues of the transgenic mice. In this paper we describe ABP gene expression in ovaries of transgenic mice that contain the rat gene; a lower level of ABP mRNA was also detected in the transgenic uterus. Northern blot analysis also detected ABP mRNA in rat ovary. The hybridizing species in the rat and transgenic mouse ovaries and uteri were the size of testicular ABP mRNA (1.7 kb). Except in the transgenic mouse brain, there was no detectable hybridizing RNA in the other transgenic tissues examined. The plasma, ovary, and uterus of the transgenic mice all contained elevated ABP (dihydrotestosterone [DHT]-binding) activities as compared to those of wild-type littermates; other wild-type and transgenic tissues were negative for DHT binding. Immunohistochemistry revealed increased immunoreactivity in the transgenic oviduct and uterus, but not the ovary. In the oviduct, the intense immunoreactivity was associated with the epithelium, whereas in the uterus it was primarily associated with the luminal epithelium and glands. Phenotypic abnormalities of the homozygous transgenic mice included reduced fecundity resulting in small litters. We conclude that ABP may function in the female reproductive system to increase the local concentrations of sex steroids or to sequester them in key target organs. Studies in the female will aid in elucidating the functions of ABP in male and female reproduction.