Discovery of a spermatogenesis stage-specific ornithine decarboxylase antizyme: Antizyme 3

Previous studies with mice overproducing ornithine decarboxylase have demon strated the importance of polyamine homeostasis for normal mammalian sperma togenesis. The present study introduces a likely key player in the maintena nce of proper polyamine homeostasis during spermatogenesis. Antizyme 3 is a paralog of mammalian ornithine decarboxylase antizymes. Like its previousl y described counterparts, antizymes 1 and 2, it inhibits ornithine decarbox ylase, which catalyzes the synthesis of putrescine. Earlier work has shown that the coding sequences for antizymes 1 and 2 are in two different, parti ally overlapping reading frames. Ribosomes translate the first reading fram e, and just before the stop codon for that frame, they shift to the second reading frame to synthesize a trans-frame product. The efficiency of this f rameshifting depends on polyamine concentration, creating an autoregulatory circuit. Antizyme 3 cDNA has the same arrangement of reading frames and a potential shift site with definite, although limited, homology to its evolu tionarily distant antizyme 1 and 3 counterparts. In contrast to antizymes 1 and 2, which are widely expressed throughout the body, antizyme 3 transcri ption is restricted to testis germ cells. Expression starts early in spermi ogenesis and finishes in the late spermatid phase. The potential significan ce of antizyme 3 expression during spermatogenesis is discussed in this pap er.