ENDOTHELIN-1 AND ITS RECEPTORS IN HUMAN TESTIS

We have previously found the presence of endothelin (ET) receptor and ET-like immunoreactivity in rat testis. We now extend our studies from rat to human testis. We found expression of a specific transcript for ET-1 and ET-1-like immunoreactivity in human testis. Positive stainin g was confined to the Sertoli cells of the tubular compartment, althou gh few peritubular and interstitial cells were also stained. We also i dentified specific ET(A) and ET(B) receptor transcripts in human testi s; ET(A) expression was more abundant than the ET(B) expression. Mathe matical analysis of multiple self-and cross-competition studies among [I-125]ET-1, [I-125]ET-3, and analogues confirmed the presence of the ET(A) and ET(B) isoreceptors. in testicular homogenates, the ET(A) rec eptor was sevenfold more concentrated than the ET(B) receptor. In orde r to localize the receptors, we performed [I-125]ET-1 autoradiography. Binding sites were mostly concentrated into the seminiferous tubules, although interstitial and peritubular myoid cells were also positive. Within the seminiferous tubules, [I-125]ET-1 binding sites were confi ned to primary and secondary spermatocytes and early spermatids, where as Sertoli cells were negative. We were unable to demonstrate the pres ence of functional ET receptors in ejaculated spermatozoa. Because ET- like immunoreactivity was present in Sertoli cells, we next asked whet her authentic ET-1 is present in human seminal fluid and represents a good index for Sertoli cell function. Reverse-phase high-performance l iquid chromatography analysis of ET-like immunoreactivity in seminal f luid indicated that most of the detected peptides correspond to the ET -1 precursor, big-ET-1. The seminal concentration of ET-like immunorea ctivity was similar in normospermic, oligospermic, azoospermic, and va sectomized men, indicating that ETs are produced in different parts of the male genital tract and that they do not represent an useful tool far the diagnosis of male reproductive diseases. In conclusion, this s tudy demonstrated, for the first time, the presence of ET-1 and its re ceptors in human testis.