ENDOTHELIN-1 - A NEW AUTOCRINE PARACRINE FACTOR IN RAT TESTIS

Cultured Sertoli cells of 20-day old rats were found to produce and re lease endothelin-1-like immunoreactivity (ET-1-LI) under follicle-stim ulating hormone control. The elution profile of ET-1-LI from extracts of spent Sertoli cell culture medium corresponds to that of synthetic ET-1, suggesting a testicular production of authentic ET-1. In contras t, the conditioned medium from rat Leydig cells did not contain ET-1-L I. Immunohistochemical studies confirmed that, in 20-day-old rats, the positive staining was confined to some Sertoli cells, whereas interst itial cells were negative. In the adult rat testis the positivity was not limited to the tubular compartment (Sertoli cells) but was also pr esent in the interstitium. A high concentration (13 pmol/mg protein) o f high-affinity (dissociation constant = 0.6 nM) I-125-labeled ET-1 bi nding sites was present in Leydig cells. These sites bind ET-1 and ET- 2 with 1,000-fold higher affinity than ET-3, suggesting that they corr espond to the subtype ET(A) of the ET receptors. Specific I-125-ET-1 b inding sites are present also in Sertoli cells but are 50-fold less co ncentrated than in Leydig cells. Our results suggest an autocrine/para crine role for ET-1 in rat testis.