Spermatogenesis is thought to critically depend on the high intratesticular
testosterone (T) levels induced by gonadotropic
hormones. Strategies for hormonal
male contraception are based on disruption of this regulatory mechanism through blockage of
gonadotropin secretion. Although exogenous T or T plus
progestin treatments efficiently block
gonadotropin secretion and suppress testicular T production, only approximately 60% of treated Caucasian men reach
contraceptive azoospermia. We now report that in
luteinizing hormone receptor knockout mice, qualitatively full spermatogenesis, up to elongated spermatids of late stages 13-16, is achieved at the age of 12 months, despite absent
luteinizing hormone action and very low intratesticular T (2% of control level). However, postmeiotic spermiogenesis was blocked by the
antiandrogen flutamide, indicating a crucial role of the residual low testicular T level in this process. The persistent
follicle-stimulating hormone action in
luteinizing hormone receptor knockout mice apparently stimulates spermatogenesis up to postmeiotic round spermatids, as observed in
gonadotropin-deficient rodent models on
follicle-stimulating hormone supplementation. The finding that spermatogenesis is possible without a
luteinizing hormone-stimulated high level of intratesticular T contradicts the current dogma. Extrapolated to humans, it may indicate that only total abolition of testicular
androgen action will result in consistent
azoospermia, which is necessary for effective
male contraception.