Direct Action through the Sertoli Cells Is Essential for Androgen Stimulation of Spermatogenesis

TLDR

Androgens stimulate spermatogenesis through androgen receptors on Sertoli and peritubular myoid cells, and loss of AR in either cell type severely disrupts spermatogenesis. The study sought to determine whether androgen stimulation of spermatogenesis requires direct action on Sertoli cells or can occur via peritubular myoid cells alone. Researchers treated hpg.ARKO and hpg.SCARKO mice with testosterone or dihydrotestosterone for seven days and assessed testicular morphology and cell counts. Androgen treatment did not change Sertoli cell numbers; testosterone and dihydrotestosterone increased spermatogonia and spermatocytes in hpg mice, but only testosterone raised germ cells in AR‑deficient mice through FSH stimulation, showing that direct androgen action on Sertoli cells is essential for spermatogenesis.

Abstract

Androgens act to stimulate spermatogenesis through androgen receptors (ARs) on the Sertoli cells and peritubular myoid cells. Specific ablation of the AR in either cell type will cause a severe disruption of spermatogenesis. To determine whether androgens can stimulate spermatogenesis through direct action on the peritubular myoid cells alone or whether action on the Sertoli cells is essential, we crossed hypogonadal (hpg) mice that lack gonadotrophins and intratesticular androgen with mice lacking ARs either ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). These hpg.ARKO and hpg.SCARKO mice were treated with testosterone (T) or dihydrotestosterone (DHT) for 7 d and testicular morphology and cell numbers assessed. Androgen treatment did not affect Sertoli cell numbers in any animal group. Both T and DHT increased numbers of spermatogonia and spermatocytes in hpg mice, but DHT has no effect on germ cell numbers in hpg.SCARKO and hpg.ARKO mice. T increased germ cell numbers in hpg.SCARKO and hpg.ARKO mice, but this was associated with stimulation of FSH release. Results show that androgen stimulation of spermatogenesis requires direct androgen action on the Sertoli cells.