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 orally a group of five normal males 2.5 mgs of CGP 47645, a long-acting nonsteroidal aromatase inhibitor (AI), once every 5 days for over 150 days. Such treatment resulted in a 10-fold increment in nocturnal serum testosterone (T) levels, which were sustained for 85 days of treatment, and a twofold increment in basal serum T levels was present throughout the 150 days of treatment. Analysis of ejaculated semen showed a marked reduction (approximately 90%) in sperm counts in four out of five monkeys between Days 55-85 of treatment. During this period, the motility score also was markedly reduced from a normal score of 3-5 to 0-2. Flow cytometric analysis of testicular germ cells obtained from biopsy tissue taken on Days 63 and 120 indicated a marked reduction only in elongating/elongated spermatid population (compared to Day 0 values), suggesting inhibition in spermiogenic process. Epididymal sperm maturation also seemed effected as sperm chromatin, on flow cytometric analysis for decondensability following exposure to 5 mM dithiotreitol, showed to be in a hypercondensed state. This study thus indicates that estrogen has an important role in providing normal testicular and sperm function in the primate.
Shetty
G
G
Department of Molecular Reproduction Development and Genetics Indian Institute of Science, Bangalore, India.
Krishnamurthy
H
H
Krishnamurthy
H N
HN
Bhatnagar
A S
AS
Moudgal
N R
NR
D000284:Administration, Oral; D000818:Animals; D047072:Aromatase Inhibitors; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D003634:DDT / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004965:Estrogen Antagonists / Q000008:administration & dosage; D005260:Female; D007275:Injections, Intravenous; D007986:Luteinizing Hormone / Q000008:administration & dosage; D008255:Macaca radiata; D008297:Male; D009570:Nitriles / Q000008:administration & dosage*; D012661:Semen / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D013739:Testosterone / Q000097:blood; D013995:Time; D014230:Triazoles / Q000008:administration & dosage*
D047072:Aromatase Inhibitors; D002843:Chromatin; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D009570:Nitriles; D014230:Triazoles; D013739:Testosterone; D007986:Luteinizing Hormone; D003634:DDT; C080901:leflutrozole