Corticosterone does not cause testicular toxicopathology in the rat: relevance to methylxanthines, ACTH and stress.
1. Methylxanthines, ACTH and stress are well known to produce testicular pathology (e.g. seminiferous tubule atrophy). Methylxanthines, ACTH and stress alter hormone secretion, particularly from the pituitary-adrenocortical system. Consequently, it has recently been suggested that there may be a causal relationship between changes in endogenous physiological adrenocortical secretions, particularly corticosterone, and testicular pathology. 2. This study tested the hypothesis that corticosterone mediates the testicular effects of both methylxanthine treatment and stress. Corticosterone was administered daily by subcutaneous injection to groups of 10 male rats at dose levels of 2 or 20 mg kg-1 in propylene glycol (1 ml kg-1) for 1 month (the shortest duration of methylxanthine or ACTH exposure known to produce testicular pathology). The highest dose of corticosterone resulted in plasma concentrations that closely matched values resulting from stress (200-700 ng ml-1) compared with controls (< 25 ng ml-1). 3. The highest dose of corticosterone caused reduced body weight gain, lower thymus, adrenal, seminal vesicle and prostate weights, but did not induce any testicular pathology. 4. That a high, but physiologically relevant, dose of corticosterone did not cause testicular pathology in this experiment excludes this steroid in the direct aetiology of methylxanthine, ACTH and stress-induced testicular pathology. Other steroids secreted from the adrenal, in combination with corticosterone, may be involved.
Schering Agrochemicals Limited, Safety Evaluation Department, Chesterford Park Research Station, Saffron Walden, Essex, UK.
P W
PW
Harvey
J
J
Er
C
C
Fernandes
K C
KC
Rush
I R
IR
Major
A
A
Cockburn
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000187:drug effects* / Q000473:pathology; D013312:Stress, Physiological; D013737:Testis / Q000187:drug effects; D014970:Xanthines / Q000633:toxicity*
D014970:Xanthines; C008514:methylxanthine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone