EFFECT OF LONG-TERM TREATMENT WITH AROMATASE INHIBITOR ON TESTICULAR FUNCTION OF ADULT MALE BONNET MONKEYS (M-RADIATA)

The role/need for estrogen in regulating testicular function of adult male bonnet monkeys (M. radiata) has been investigated by dosing orall y a group of five normal males 2.5 mgs of CGP 47645, a long-acting non steroidal aromatase inhibitor (AI), once every 5 days for over 150 day s. Such treatment resulted in a 10-fold increment in nocturnal serum t estosterone (T) levels, which were sustained for 85 days of treatment, and a twofold increment in basal serum T levels was present throughou t the 150 days of treatment. Analysis of ejaculated semen showed a mar ked reduction (similar to 90%) in sperm counts in four out of five mon keys between Days 55-85 of treatment. During this period, the motility scare also was markedly reduced from a normal score of 3-5 to 0-2. Fl ow cytometric analysis of testicular germ cells obtained from biopsy t issue taken on Days 63 and 120 indicated a marked reduction only in el ongating/elongated spermatid population (compared to Day 0 values), su ggesting inhibition in spermiogenic process. Epididymal sperm maturati on also seemed effected as sperm chromatin, on flow cytometric analysi s for decondensability following exposure to 5 mM dithiotreitol, showe d to be in a hypercondensed state. This study thus indicates that estr ogen has an important role in providing normal testicular and sperm fu nction in the primate. (C) 1996 by Elsevier Science Inc.