Alcohol alters insulin-like growth factor-1 activated oct 2 POU domain gene expression in the immature female hypothalamus.
OBJECTIVE
The Oct 2 POU homeodomain gene has been shown to increase during late juvenile development; the upstream control of Oct 2 is not known, however. The insulin-like growth factor-1 (IGF-1) is known to act centrally to stimulate luteinizing hormone (LH)-releasing hormone (LHRH) release and advance female puberty. We therefore sought to determine if this peptide induces transcription of Oct 2 genes as an early pubertal event. Furthermore, as alcohol (ALC) blocks IGF-1-induced LHRH and LH release acutely, we aimed to determine if it could affect the ability of IGF-1 to stimulate Oct 2 gene expression.


METHODS
Female rats, 25 days old, were administered saline or IGF-1 (rat IGF-1 20 ng/3 microI) in the third ventricle at 0900 hours and killed 2, 4 and 6 hours later for assessment of Oct 2 gene expression in the preoptic area (POA) and the medial basal hypothalamus (MBH). In another experiment, we determined whether ALC (3 g/kg) could block IGF-1-induced Oct 2 gene expression.


RESULTS
In the POA, IGF-1 did not affect the expression of Oct 2a, but it increased the Oct 2c mRNA levels at 2 hours. In the MBH, both transcripts were elevated 4 hours after IGF-1 stimulation. ALC did not alter basal expression of either of the Oct 2 gene isoforms. In both regions, however, ALC blocked IGF-1-induced gene expression.


CONCLUSIONS
IGF-1 induced Oct 2 genes prior to the normal increase during the late juvenile period, indicating this IGF- 1 induction may be an early event in the activation of the LHRH secretory pathway. ALC blocks this action, suggesting the Oct 2 POU gene is a likely target by which ALC can interfere with glial-neuronal interactions and interrupt LHRH secretion during prepubertal development.
Dees
W Les
WL
Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4458, USA. ldees@cvm.tamu.edu
Srivastava
Vinod K
VK
Hiney
Jill K
JK
D000199:Actins / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000235:genetics*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D050813:Octamer Transcription Factor-2; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics*
D000199:Actins; D004268:DNA-Binding Proteins; D050813:Octamer Transcription Factor-2; C489205:Pou2f2 protein, rat; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone