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Alcohol alters insulin-like growth factor-1-induced transforming growth factor beta1 synthesis in the medial basal hypothalamus of the prepubertal female rat.

Authors: Hiney, JK  Srivastava, VK  Volz, CE  Dees, WL 
Citation: Hiney JK, etal., Alcohol Clin Exp Res. 2014 Oct;38(10):2572-8. doi: 10.1111/acer.12534. Epub 2014 Oct 21.
Pubmed: (View Article at PubMed) PMID:25335926
DOI: Full-text: DOI:10.1111/acer.12534

BACKGROUND: Insulin-like growth factor-1 (IGF-1) and transforming growth factor beta1 (TGFbeta1) are produced in hypothalamic astrocytes and facilitate luteinizing hormone-releasing hormone (LHRH) secretion. IGF-1 stimulates release by acting directly on the LHRH nerve terminals and both peptides act indirectly through specific plastic changes on glial/tanycyte processes that further support LHRH secretion. Because the relationship between these growth factors in the hypothalamus is not known, we assessed the ability of IGF-1 to induce TGFbeta1 synthesis and release and the actions of alcohol (ALC) on this mechanism prior to the onset of puberty. METHODS: Hypothalamic astrocytes were exposed to medium only, medium plus IGF-1 (200 ng/ml), or medium plus IGF-1 with 50 mM ALC. After 18 hours, media were collected and assayed for TGFbeta1. For the in vivo experiment, prepubertal female rats were administered either ALC (3 g/kg) or water via gastric gavage at 07:30 hours and at 11:30 hours. At 09:00 hours, saline or IGF-1 was administered into the third ventricle. Rats were killed at 15:00 hours and the medial basal hypothalamus (MBH) was collected for assessment of TGFbeta1, IGF-1 receptor (IGF-1R), and Akt. RESULTS: IGF-1 induced TGFbeta1 release (p < 0.01) from hypothalamic astrocytes in culture, an action blocked by ALC. In vivo, IGF-1 administration caused an increase in TGFbeta1 protein compared with controls (p < 0.05), an action blocked by ALC as well as a phosphatidylinositol 3 kinase/Akt inhibitor. IGF-1 stimulation also increased both total (p< 0.01) and phosphorylated (p)-IGF-1R (p < 0.05) protein levels, and phosphorylated (p)-Akt levels (p < 0.01), which were also blocked by ALC. CONCLUSIONS: This study shows that ALC blocks IGF-1 actions to stimulate synthesis and release of hypothalamic TGFbeta1, total and p-IGF-1R, and p-Akt levels further demonstrating the inhibitory actions of ALC on puberty-related events associated with hypothalamic LHRH release.


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CRRD Object Information
CRRD ID: 11073673
Created: 2016-05-03
Species: All species
Last Modified: 2016-05-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.