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Alcohol Alters Insulin‐Like Growth Factor‐1‐Induced Transforming Growth Factor β1 Synthesis in the Medial Basal Hypothalamus of the Prepubertal Female Rat
Author(s) -
Hiney Jill K.,
Srivastava Vinod K.,
Volz Claire E.,
Dees William L.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12534
Subject(s) - endocrinology , medicine , hypothalamus , growth factor , insulin like growth factor , transforming growth factor , in vivo , chemistry , biology , receptor , microbiology and biotechnology
Background Insulin‐like growth factor‐1 (IGF‐1) and transforming growth factor β1 (TGFβ1) 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 TGFβ1 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 TGFβ1. 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 TGFβ1, IGF‐1 receptor (IGF‐1R), and Akt. Results IGF‐1 induced TGFβ1 release ( p < 0.01) from hypothalamic astrocytes in culture, an action blocked by ALC. In vivo, IGF‐1 administration caused an increase in TGFβ1 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 TGFβ1, 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.