Abstract:
Androgen receptor function is required for male embryonic sexual
differentiation, pubertal development and the regulation of
spermatogenesis in mammals. During spermatogenesis, this requirement is
thought to be mediated by Sertoli cells and its genetic and
pharmacological disruption is manifested in spermatocytes as meiotic
arrest. Through studies of a hypomorphic and conditional allele of the
androgen receptor (Ar) gene, we have uncovered a dual post-meiotic
requirement for androgen receptor activity during male germ cell
differentiation. Observations in Ar hypomorphic animals demonstrate that
terminal differentiation of spermatids and their release from the
seminiferous epithelium is AR dependent and maximally sensitive to AR
depletion within the testis. Cell-specific disruption of Ar in Sertoli
cells of hypomorphic animals further shows that progression of late-round
spermatids to elongating steps is sensitive to loss of Sertoli cell AR
function, but that progression through meiosis and early-round spermatid
differentiation are surprisingly unaffected.
