Failure of ethanol metabolites to alter gonadotropin secretion or luteinizing hormone synthesis in vitro.
The impact of ethanol on the male reproductive axis are multiple and varied, with both gonadal and control hypothalamic-pituitary pertubations being reported. There appears to be a discrepancy, however, between the in vivo and in vitro effects of ethanol on hypothalamic luteinizing hormones releasing hormone (LHRH) and the pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH). While in vivo data suggests a decrease in LHRH release after EtOH, in vitro studies find no effect on secretion. Similarly, in vivo acute EtOH profoundly diminishes LH synthesis and secretion, while in vitro impaired release with no alteration in the transcription of beta LH has been found. A potential exploration for these discrept results could be the in vivo metabolism of EtOH into acetaldehyde and acetate, or the subsequent formation of salsolinol, a product of acetate combining with dopamine. To test this possibility, a series of in vitro experiments were conducted exposing dispensed anterior pituitary cells from male rats to different doses of acetaldehyde, acetate or salsolinol for varying amounts of time for which gonadotropin secretion and beta LH mRNA levels were assessed. The results demonstrated no effect of either acetaldehyde or acetate on basal or LHRH stimulated LH release, FSH release or steady-state beta LH mRNA levels. These data suggest that the metabolites of EtOH, which occur in vivo but not in vitro, are not responsible for the discrepant gonadotropin changes reported between the in vivo and in vitro setting. Other potential mechanisms to explain this phenomenon include differences in the molarity of EtOH, hyperprolactinemia and suprapituitary influences including hypothalamic LHRH, catecholamines, excitatory amino acids, substance P and beta endorphin.
Uddin
S
S
Department of Veteran Affairs, Edward Hines Jr. Hospital, Hines, IL 60141, USA.
Kirsteins
L
L
LaPaglia
N
N
Emanuele
N V
NV
Lawrence
A M
AM
Kelley
M R
MR
Emanuele
M A
MA
D000079:Acetaldehyde / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism*; D037201:Follicle Stimulating Hormone, beta Subunit; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D037201:Follicle Stimulating Hormone, beta Subunit; D007546:Isoquinolines; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D000431:Ethanol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C036617:salsolinol; D000079:Acetaldehyde