Failure of ethanol to induce changes in gonadotropin gene expression in selectively bred ethanol-sensitive rats.
The recent availability of genetically altered rat lines differing in sensitivity to ethanol (EtOH) has allowed deeper investigation into the mechanisms of EtOH-induced cellular toxicity in several systems. Since the male central reproductive axis has been demonstrated to be exquisitely sensitive to EtOH, studies were undertaken to determine if the gonadotropin suppression reported earlier could be duplicated in one of these selected rat lines. Castrated high alcohol sensitivity (HAS), low alcohol sensitivity (LAS) and control alcohol sensitivity (CAS) rats were given EtOH or saline acutely. Castrated non-selectively bred Sprague Dawley rats were treated similarly and used as an additional control. At sacrifice, serum and pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were obtained and the mRNA levels for both gonadotropins assessed. In the selectivity bred animal there was essentially no change in serum or pituitary LH or FSH levels between EtOH and saline treated animals. The mRNA levels for both LH and FSH similarly were unaffected by EtOH, in striking contrast to the non-selectively bred Sprague Dawley rats where serum LH, FSH and beta-LH mRNA levels are markedly suppressed after EtOH exposure. The selectively bred lines of rats genetically manipulated for high or low EtOH sensitivity, as well as their non-selected controls, appeared to have a hypothalamic-pituitary reproductive unit that is resistant to EtOH. This is in contrast to Sprague-Dawley rats, where suppression of this axis previously has been consistently demonstrated.
Halloran
M M
MM
Department of Molecular and Cellular Biochemistry, Loyola University of Chicago, Stritch School of Medicine, Maywood, IL 60153.
Emanuele
M A
MA
Draski
L
L
Tentler
J J
JJ
Emanuele
N V
NV
Kelley
M R
MR
D000818:Animals; D004342:Drug Hypersensitivity / Q000235:genetics*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000032:analysis / Q000097:blood / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006062:Gonadotropins / Q000032:analysis / Q000097:blood / Q000235:genetics*; D007986:Luteinizing Hormone / Q000032:analysis / Q000097:blood / Q000235:genetics; D008297:Male; D010902:Pituitary Gland / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood
D006062:Gonadotropins; D012333:RNA, Messenger; D000431:Ethanol; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone