Liver and kidney growth hormone (GH) receptors are regulated differently in diabetic GH and GH antagonist transgenic mice.
Elevated GH levels are frequently seen in poorly controlled type I diabetics and have been implicated in diabetic complications. Studies of GH and GH antagonist (GHA) transgenic mice with streptozotocin (STZ)-induced diabetes have revealed that GH has a permissive effect for diabetic nephropathy, and that expression of a GHA gene protected mice against diabetic kidney lesions. To investigate whether kidney GH receptor (GHR) and/or GH-binding protein may play a role in diabetic nephropathy, we evaluated GH-specific binding and messenger RNA levels for GHR/GH-binding protein in mouse livers and kidneys from bovine (b) GH or bGHA transgenic (Tg) mice and their nontransgenic (NTg) littermates with or without STZ-induced diabetes. We found that liver-specific GH binding is significantly higher in both bGH- and bGHA-Tg mice compared to that in their NTg controls. In contrast, kidney GH binding is significantly lower in bGH-Tg mice compared to that in NTg littermates. These results indicate that regulation of mouse GHR expression is tissue specific. STZ-induced diabetes decreased GH-specific binding in both liver and kidney of NTg and GHA-Tg mice, but not in bGH-Tg mice. The lowered GHR binding in diabetic NTg and GHA-Tg mice suggests the involvement of insulin in the regulation of GHR expression. The down-regulation of kidney GHR in GHA-Tg mice in combination with the presence of GHA may partially explain the protective mechanism of GHA against diabetic kidney lesions.
Chen
N Y
NY
Department of Clinical Research, Ohio University College of Osteopathic Medicine, Athens 45701, USA.
Chen
W Y
WY
Kopchick
J J
JJ
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics*
D002352:Carrier Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D013006:Growth Hormone; C051815:somatotropin-binding protein