Ghrelin treatment protects lactotrophs from apoptosis in the pituitary of diabetic rats.
Poorly controlled diabetes is associated with hormonal imbalances, including decreased prolactin production partially due to increased lactotroph apoptosis. In addition to its metabolic actions, ghrelin inhibits apoptosis in several cell types. Thus, we analyzed ghrelin's effects on diabetes-induced pituitary cell death and hormonal changes. Six weeks after onset of diabetes in male Wistar rats (streptozotocin 70 mg/kg), minipumps infusing saline or 24 nmol ghrelin/day were implanted (jugular). Rats were killed two weeks later. Ghrelin did not modify body weight or serum glucose, leptin or adiponectin, but increased total ghrelin (P<0.05), IGF-I (P<0.01) and prolactin (P<0.01) levels. Ghrelin decreased cell death, iNOS and active caspase-8 (P<0.05) and increased prolactin (P<0.05), Bcl-2 (P<0.01) and Hsp70 (P<0.05) content in the pituitary. In conclusion, ghrelin prevents diabetes-induced death of lactotrophs, decreasing caspase-8 activation and iNOS content and increasing anti-apoptotic pathways such as pituitary Bcl-2 and Hsp70 and serum IGF-I concentrations.
Granado
M
M
Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.
Chowen
J A
JA
García-Cáceres
C
C
Delgado-Rubín
A
A
Barrios
V
V
Castillero
E
E
Argente
J
J
Frago
L M
LM
D052242:Adiponectin / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology*; D054439:Ghrelin / Q000097:blood / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D052682:Lactotrophs / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D020738:Leptin / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D015430:Weight Gain / Q000187:drug effects; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D052242:Adiponectin; D015415:Biomarkers; D054439:Ghrelin; D018840:HSP70 Heat-Shock Proteins; D007328:Insulin; D020738:Leptin; D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D052247:Nitric Oxide Synthase Type II; D020169:Caspases