A ROLE FOR NOCTURNAL SERUM TESTOSTERONE SURGE IN REGULATING SPERMATOGENESIS IN THE ADULT NONHUMAN PRIMATE

Adult male bonnet monkeys exhibit nychthemeral rhythms in testosterone (T) secretion but the precise role of this heightened level of T secr etion in regulating spermatogenesis is not known. Intranasal administr ation of microdoses (500 mu g or 250 mu g/day) of Norethisterone (IN-N ET) to adult monkeys (n = 6) at 1600 h each day selectively and comple tely suppressed the nocturnal surge levels of serum T. Concomitant wit h this was a significant reduction (P<0.01) in serum LH but not FSH le vels. DNA flow cytometric analysis of testicular biopsy tissue showed by week 10 of IN-NET treatment an arrest in meiotic transformation of primary spermatocytes (4C) to round/elongate (1C/HC) spermatids and by week 20 there was a complete absence of 4C, 1C and HC cells (with a r elative accumulation in 2C cells). The accumulated meiotic (4C) cells at week 10 showed an increase (>80%, P<0.01) in coefficient of variati on and a decrease in intensity of DNA-bound ethidium bromide fluoresce nce, parameters characteristic of degenerating 'apoptotic' subpopulati on of germ cells. While two monkeys exhibited acute oligozoospermia 4 became azoospermic by 20 weeks of IN-NET treatment. A complete, qualit ative reversal in the regressive changes in spermatogenesis and near-n ormal sperm output were apparent at the end of a 20-week recovery phas e. These data demonstrate that prolonged, selective suppression of noc turnal surge levels of serum T secretion exerts a primary effect on me iosis in spermatogenesis leading to oligo/azoospermic status in adult bonnet monkeys.