Progressive induction of mRNA synthesis for androgen-responsive genes in mouse kidney

A number of mRNAs present in kidney are selectively induced by the administration of androgen to mice. Using a pulse-labelling method to measure in vivo rates of mRNA synthesis, seven androgen-responsive mRNAs were tested. The time courses of induction following testosterone treatment indicated that androgen-responsive mRNA synthesis increases progressively. Depending on the mRNA examined, it took 2-10 days after the start of hormone administration for synthesis rates to reach a maximum. Even the fastest of these inductions is slow compared to response times in other steroid-responsive systems, and is very slow compared to the time required for androgen-receptor complex to accumulate in the nucleus. We conclude that gene activation in response to androgen is a prolonged and incremental process rather than a single event. Two alternative models are proposed: (1) these genes are actually responding to intermediate transcription factors that accumulate progressively in response to androgen; (2) the androgen-responsive genes contain multiple binding sites that have a cumulative effect on transcription as the number of receptor complexes bound increases.