Actions of ethanol on epidermal growth factor receptor activated luteinizing hormone secretion.
OBJECTIVE
Activation of the epidermal growth factor receptor (EGF-R) stimulates prepubertal luteinizing hormone-releasing hormone (LHRH) release, which in turn induces luteinizing hormone (LH) secretion. Although ethanol (ETOH) diminishes LHRH secretion and delays the onset of female puberty, its actions following EGF-R activation are unknown. We therefore investigated the effects of ETOH on EGF-induced LHRH and LH release, both in vivo and in vitro.


METHODS
Basal blood samples were taken every 15 minutes from immature female rats, which then received ETOH (3 g/kg) or saline by gastric gavage. After a 90-minute ETOH absorption period, a single blood sample was drawn from each rat. Finally, EGF (200 ng/3 microl) was injected into the third ventricle of all animals and postinjection samples were drawn every 15 minutes. A similar experimental design was performed except no blood samples were taken. After ETOH exposure, EGF was administered, and 45 minutes later the animals were killed and their medial basal hypothalamus and pituitary were removed and analyzed for EGF-R and cyclooxygenase (COX) 1 and 2 by western blot analysis. For in vitro experiment, median eminence fragments from immature female rats were exposed to ETOH in a static incubation system, and prostaglandin-E, (PGE2) and LHRH were measured.


RESULTS
EGF stimulated LH release, and this release was blunted (p < .05) by ETOH. Western blot analysis revealed that ETOH did not alter the EGF-R protein levels in the hypothalamus. ETOH blocked EGF-induced PGE2 and LHRH released from isolated median eminences. EGF administration increased both COX-1 (p < .001) and COX-2 (p < .01), but both enzymes were blocked by ETOH.


CONCLUSIONS
The ETOH-induced decrease in EGF-stimulated LH release is due to a reduction in the formation of hypothalamic PGE2 and, subsequently, suppressed LHRH release.
Hiney
J K
JK
Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine, College Station, Texas 77843-4458, USA. Jhiney@cvm.tamu.edu
Dearth
R K
RK
Srivastava
V
V
Rettori
V
V
Dees
W L
WL
D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D066246:ErbB Receptors