Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective (SCARKO) or total (ARKO) ablation of the androgen receptor

Abstract

It is established that androgens and unidentified Sertoli cell (SC) -derived factors can influence development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size by ∼2-fold between 12 and 140 days of age. LC number in SCARKOs was normal at d 12 but was reduced by >40% at later ages though LC size was larger and contained more lipid droplets and mitochondria than did control LC by adulthood. ARKO LC number was reduced by up to 83% at all ages compared with controls and LC size did not increase beyond d 12. Serum LH and testosterone levels and seminal vesicle weights were comparable in adult SCARKOs and controls, whereas LH levels were elevated 8-fold in ARKOs, though testosterone levels appeared normal. Immunohistochemistry and quantitative PCR for LC-specific markers indicated steroidogenic function per LC was probably increased in SCARKOs and reduced in ARKOs. In SCARKOs, Insulin-like factor 3 and estrogen sulfotransferase (EST) mRNA expression were unchanged and increased 3-fold, respectively, compared with controls, whereas expression of both was reduced >90% in ARKOs. Changes in EST expression, coupled with reduced PDGF-A expression, are potential causes of altered LC number and function in SCARKOs. These results show that loss of androgen action on SC has major consequences for LC development and this could be mediated indirectly via PDGF-A and/or estrogens/EST. Copyright © 2005 by The Endocrine Society.