Effects of a high-glucose environment on the pituitary growth hormone-releasing hormone receptor: type 1 diabetes compared with in vitro glucotoxicity

Autor: Pierrette Gaudreau, Julie Bédard, Karine Bédard, Christelle Veyrat-Durebex, Julie Strecko, Karyne Theriault
Rok vydání: 2008
Předmět:
Male
Receptors
Neuropeptide
endocrine system
medicine.medical_specialty
Pituitary gland
Physiology
Endocrinology
Diabetes and Metabolism
Stimulation
Apoptosis
Biology
In Vitro Techniques
Growth Hormone-Releasing Hormone
Diabetes Mellitus
Experimental
Iodine Radioisotopes
Rats
Sprague-Dawley
Necrosis
Radioligand Assay
Anterior pituitary
Receptors
Pituitary Hormone-Regulating Hormone
Pituitary Gland
Anterior
Physiology (medical)
Internal medicine
medicine
Cyclic AMP
Animals
RNA
Messenger
Insulin-Like Growth Factor I
Receptor
Cells
Cultured
Diminution
Growth hormone–releasing hormone
Fluoresceins
Rats
Oxidative Stress
Endocrinology
medicine.anatomical_structure
Diabetes Mellitus
Type 1
Glucose
Hypothalamus
Hormone receptor
Lipid Peroxidation
hormones
hormone substitutes
and hormone antagonists
Zdroj: American journal of physiology. Endocrinology and metabolism. 294(4)
ISSN: 0193-1849
Popis: The present study investigated the effects of diabetes and high glucose on GHRH receptor (GHRH-R) mRNA and protein levels in the pituitary of diabetic rats 2, 21, and 60 days post-streptozotocin (post-STZ) administration. Two days post-STZ, the 2.5-kb GHRH-R mRNA transcript was increased. Twenty-one days post-STZ, both the 2.5- and 4-kb transcripts and a 72-kDa 125I-GHRH-GHRH-R complex were elevated. Sixty days post-STZ, the 4-kb transcript remained increased and the 45-kDa 125I-GHRH-GHRH-R complex (functional receptor) was decreased. Hypothalamic GHRH mRNA and serum total IGF-I levels were reduced at all three time points. To better understand the role of high glucose on GHRH-R regulation, time-course effects of 33 compared with 6 mM d-glucose (DG) were examined in cultured anterior pituitary cells from 2-mo-old healthy rats. Membrane lipoperoxidation was present in 33 mM DG, and GHRH-R mRNA levels were diminished after 24 h, Fluo-GHRH internalization was marginal after 16–24 h, and GHRH-induced cAMP levels were decreased after 24 and 48 h. Altogether, these results indicate that the increase of the 2.5-kb GHRH-R mRNA transcript in vivo could be a consequence of a decrease of hypothalamic GHRH mRNA levels in STZ rats. Since it does not affect primarily functional GHRH-R levels, the initial diminution of circulating IGF-I levels could result from a decreased GHRH-R stimulation by GHRH. Thus, the effect of glucotoxicity would be related to a decrease of functional GHRH-R protein, as observed in rats 60 days post-STZ and in cultured pituitary cells from healthy rats exposed to a high-glucose environment.
Databáze: OpenAIRE
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