Impaired estrogen-induced uterine insulin-like growth factor-I gene expression in the streptozotocin diabetic rat.
Circulating somatomedin-C/insulin-like growth factor-I levels are low in the diabetic rat and unresponsive to exogenous growth hormone. However, the nature of this defect in growth hormone action remains unclear and there is little data on insulin-like growth factor-I gene expression in response to other stimuli and in non-hepatic tissues where insulin-like growth factor-I may have important paracrine and/or autocrine actions. We have previously shown that 17-beta estradiol stimulates uterine insulin-like growth factor-I expression in the ovariectomised rat. In this report uterine and hepatic insulin-like growth factor-I gene expression have been examined in the streptozotocin-diabetic rat. Serum insulin-like growth factor-I concentrations were significantly reduced in diabetic rats compared to normal rats (0.72 +/- 0.08 vs 1.23 +/- 0.05 U/ml, p less than 0.0005) and hepatic insulin-like growth factor-I mRNA abundance was similarly reduced in diabetic rats to 49 +/- 5% of that seen in non-diabetic intact rats (p less than 0.005). In contrast, uterine insulin-like growth factor-I mRNA abundance was not significantly reduced in diabetic rats compared to control rats (76 +/- 12%, p = NS). Although both diabetic and non-diabetic rats demonstrated a significant increase in uterine wet weight following a single injection of 17-beta estradiol the increase in uterine insulin-like growth factor-I expression was significantly less marked in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Murphy
L J
LJ
Department of Medicine and Physiology, University of Manitoba, Winnipeg, Canada.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005796:Genes / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013002:Somatomedins / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D013002:Somatomedins; D004958:Estradiol; D007334:Insulin-Like Growth Factor I