Transmembrane Versus Soluble Stem Cell Factor Expression in Human Testis

Abstract

ABSTRACT: The interaction between stem cell factor (SCF), a ligand produced by Sertoli cells, and its c‐kit receptor on germ cells is necessary for successful spermatogenesis in animal models. SCF can be alternatively spliced into soluble and transmembrane forms, and it is the transmembrane form that is required for spermatogenesis in rodents. c‐Kit receptors are also present on Leydig cells, and soluble SCF has been implicated in the regulation of testosterone production. This study had two goals: To test the hypothesis that the extent of germ cell production in human males is correlated with the expression of transmembrane SCF, and to examine the relationship between testosterone production and the expression of soluble SCF in humans. Reverse transcriptase polymerase chain reaction was used to determine the ratio of transmembrane‐to‐soluble SCF in testicular tissue. Clinical analysis, hormonal measurements, and histological methods were used to evaluate the causes of infertility and to seek correlations with the pattern of SCF expression. SCF was preferentially expressed as the transmembrane type in all testicular samples, regardless of the state of germ cell production. Furthermore, the percent of transmembrane SCF expression was independent of clinical and histopathological diagnosis (rs = −0.111, n = 28) and unrelated to the extent of spermatogenesis. This contrasts with rat models of testicular injury that exhibit a decreased proportion of transmembrane SCF with atrophy. A significant correlation (rs = 0.665, P < .02, n = 16) was found between testosterone levels and percent soluble SCF, which suggests that, in humans, there may be a regulatory interaction between soluble SCF and testosterone.