Protection of spermatogenesis by α_2u globulin in rats treated with oestrogen

Abstract

α_2u GLOBULIN is an androgen-dependent rat urinary protein with a molecular weight of about 23,800 (ref. 1). In the male rat, starting from puberty until senescence, α_2u globulin is synthesised and secreted by the hepatic tissue and is rapidly cleared by the kidneys into the urine^2–4. In addition to its urinary concentration α_2u globulin has been found to be concentrated by the salivary glands and released into the saliva (A.K.R., and J.G.B., in preparation). Synthesis of this protein could be induced in the spayed female rat by androgen, and oestrogenic compounds completely inhibited α_2u synthesis in the mature male rat⁵. But α_2u globulin does not bind testosterone, oestradiol-17β or any of their metabolites (unpublished results of A.K.R.). Pretreatment of mature male rats with oestrogen induces a dose-dependent temporary lag period within which α_2u globulin is not synthesised even under androgenic stimulation. With a daily oestradiol dose of 50 µg per 100g body weight a lag period extending up to 3–4 weeks has been established⁶. Although the adult male rat synthesises 20–30 mg of α_2u globulin per day, no physiological role of this protein has yet been established. The close parallel between the male reproductive capability and the production of α_2u globulin^4,5 prompted us to look into the possible reproductive role of this protein. The discovery of the oestrogen-mediated lag period in the mature male rats also provided an opportunity to look into the spermatogenic abnormalities within this lag period and any reparative effects which α_2u globulin may have on such damage. The results reported here demonstrate considerable protection of spermatogenesis by α_2u globulin against potential damage by oestrogen.