The interaction between stem cell factor (SCF), a ligand produced by Sertol
i cells, and its c-kit receptor on germ cells is necessary for successful s
permatogenesis in animal models. SCF can be alternatively spliced into solu
ble and transmembrane forms, and it is the transmembrane form that is requi
red for spermatogenesis in rodents. c-Kit receptors are also present on Ley
dig cells, and soluble SCF has been implicated in the regulation of testost
erone production. This study had two goals: To test the hypothesis that the
extent of germ cell production in human males is correlated with the expre
ssion of transmembrane SCF, and to examine the relationship between testost
erone production and the expression of soluble SCF in humans. Reverse trans
criptase polymerase chain reaction was used to determine the ratio of trans
membrane-to-soluble SCF in testicular tissue. Clinical analysis, hormonal m
easurements, and histological methods were used to evaluate the causes of i
nfertility and to seek correlations with the pattern of SCF expression. SCF
was preferentially expressed as the transmembrane type in all testicular s
amples, regardless of the state of germ cell production. Furthermore, the p
ercent of transmembrane SCF expression was independent of clinical and hist
opathological diagnosis (r(s) = -0.111, n = 28) and unrelated to the extent
of spermatogenesis. This contrasts with rat models of testicular injury th
at exhibit a decreased proportion of transmembrane SCF with atrophy. A sign
ificant correlation (r(s) = 0.685, P < .02, n = 16) was found between testo
sterone levels and percent soluble SCF, which suggests that, in humans, the
re may be a regulatory interaction between soluble SCF and testosterone.