The low gonadotropin-independent constitutive production of testicular testosterone is sufficient to maintain spermatogenesis

FP Zhang, T Pakarainen, M Poutanen… - Proceedings of the …, 2003 - National Acad Sciences
FP Zhang, T Pakarainen, M Poutanen, J Toppari, I Huhtaniemi
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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≈ 60% of treated
Caucasian men reach contraceptive azoospermia. We now report that in luteinizing …
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 ≈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.
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