Testosterone is synthesised mainly if not entirely by the leydig cells and secreted episodically with a slight circadian variation. Only the free, nonprotein-bound fraction of the testosterone in the circulation is biologically active. This free testosterone passes into the target cells and is taken up by specific receptors in the muscle. In some other target tissues, testosterone is first reduced to 5alpha-dihydrotestosterone which is then taken up by specific receptors in the cytoplasm and transferred to the nucleus. Anti-androgens appear to act principally by inhibiting this uptake.