Seasonal and tissue-specific regulation of canary androgen receptor messenger ribonucleic acid

Natural seasonal fluctuations in androgen levels appear to cause changes in physiology and reproductive behavior, such as singing, in canaries. Little is known, however, about the cellular mechanisms underlying these changes. Because androgens act principally through nuclear receptors in other species, we have isolated and sequenced a cDNA likely to encode the canary androgen receptor and used this cDNA to examine the regulation of AR mRNA levels in the testis, kidney, and liver of the canary. The sequence corresponds to most of the coding portion of seven of the eight exons found in the homologous mammalian gene, including the domains that bind to DNA and androgen and affect transcription. Its mRNA is approximately 8 kilobases in length and is encoded by a single gene. In the testis, the transcript is expressed specifically in the Sertoli cells. The androgen receptor antagonist flutamide represses AR mRNA levels in kidney, but induces them in liver, indicating that androgen regulates its receptor, but does so in a tissue-specific manner, as is seen for the estrogen receptor in rodents. In addition, there are natural seasonal fluctuations in AR mRNA levels in testis and liver correlated with seasonal differences in the levels of circulating androgens. This is the first evidence of natural feedback regulation of AR mRNA levels.