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

• Published in: Endocrinology (Philadelphia) 2010-05, Vol.151 (5), p.2343-2348
• Main Authors: O'Shaughnessy, P. J, Verhoeven, G, De Gendt, K, Monteiro, A, Abel, M. H
• Format: Article
• Language: English
• Subjects: Ablation; Androgen receptors; Androgens; Androgens - pharmacology; Animals; Biological and medical sciences; Cell Count; Dihydrotestosterone; Dihydrotestosterone - pharmacology; Enzyme-Linked Immunosorbent Assay; Female; Follicle Stimulating Hormone - blood; Follicle-stimulating hormone; Fundamental and applied biological sciences. Psychology; Gametocytes; Gonadotropins; Immunohistochemistry; Male; Mice; Mice, Knockout; Pituitary (anterior); Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Sertoli cells; Sertoli Cells - cytology; Sertoli Cells - drug effects; Sertoli Cells - metabolism; Spermatocytes; Spermatocytes - cytology; Spermatocytes - drug effects; Spermatocytes - metabolism; Spermatogenesis; Spermatogenesis - drug effects; Spermatogonia; Spermatogonia - cytology; Spermatogonia - drug effects; Spermatogonia - metabolism; Stimulation; Testis - cytology; Testis - drug effects; Testis - metabolism; Testosterone; Testosterone - pharmacology; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2009-1333

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. Androgens must act through Sertoli cell androgen receptors to stimulate spermatogenesis.