Influence of simultaneous gonadotropin-releasing hormone agonist and testosterone treatment on spermatogenesis and potential fertilizing capacity in male monkeys.
We examined the effect of continuous sc infusion of a GnRH agonist (Ag) and testosterone (T) supplementation on spermatogenesis and the potential fertilizing capacity of sperm in 15 rhesus monkeys. The monkeys were divided into 3 groups of 5 animals each. Groups 1 and 2 received 25 micrograms/day Ag for 44 weeks. Group 2 also received T replacement therapy [sufficient to maintain serum T values within the normal range; 4-5 ng/mL (13.9-17.3 nmol/L)]. Group 3 received a low dose of the Ag (5 micrograms/day for 24 weeks and then 10 micrograms/day for 20 weeks) to prolong the oligospermic phase before the onset of azoospermia. In groups 1 and 3, there was an initial transient (1 week) rise in serum LH and T levels which then fell below pretreatment value where they remained throughout the treatment period. The serum LH and T levels were lower in the group treated with 25 micrograms/day Ag. Similar changes in serum LH levels occurred in group 2, but T supplementation maintained serum T in the physiological range. The decline in serum LH levels was associated with reduced sensitivity to GnRH, since the responses of serum LH and T to GnRH were either abolished or greatly reduced in the 2 groups treated with 25 micrograms/day Ag and were less than 50% of the pre-Ag responses in monkeys treated with 5-10 micrograms/day Ag. Four of five monkeys treated with 25 micrograms/day Ag alone became azoospermic within 21 weeks. All five animals receiving Ag and T supplementation became azoospermic (mean time to onset, 12.6 weeks). Four of five monkeys treated with 5-10 micrograms/day Ag also had azoospermic ejaculates during the late treatment and early recovery period. Sperm counts recovered to the pretreatment levels in most monkeys by 10 weeks of the recovery period. The quality of semen samples taken from oligospermic monkeys was greatly reduced. The percentage of motile and percentage of live sperm per ejaculate, the net negative surface charge on sperm, and the scores of sperm in the hamster oocyte penetration test were subnormal. T supplementation did not improve these measures of semen quality. Testicular biopsies taken at the end of the Ag administration period from monkeys given 25 micrograms/day Ag showed diffuse atrophy of the seminiferous tubules, which contained primarily Sertoli cells and a few spermatogonia and spermatocytes, but no spermatids. The tubular atrophy and the suppression of spermatogenesis did not appear to be influenced by T replacement.(ABSTRACT TRUNCATED AT 400 WORDS)
Mann
D R
DR
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia 30310.
Gould
K G
KG
Smith
M M
MM
Duffey
T
T
Collins
D C
DC
D000818:Animals; D006224:Cricetinae; D004357:Drug Synergism; D005260:Female; D005298:Fertility / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D009845:Oligospermia / Q000139:chemically induced; D012661:Semen / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects; D013084:Sperm-Ovum Interactions / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; C030741:lutrelin acetate