Pituitary control of cholesterol metabolism in normal and LDL receptor knock-out mice: effects of hypophysectomy and growth hormone treatment.
The pituitary is important in the control of lipid metabolism and studies of hypophysectomized (Hx) rats have shown strong effects of growth hormone (GH) on bile acid synthesis, hepatic LDL receptor (LDLR) expression and on the sensitivity to dietary cholesterol. It is unclear if mice may be used in such studies. The aim of the current study was to evaluate if Hx mice may be used to further explore how GH modulates cholesterol and bile acid metabolism, and to define the importance of the LDLR in this regulation by studying LDLR-deficient mice (LDLRko). Experiments on three mouse strains showed that, following Hx, HDL were reduced and LDL increased. Cholesterol/fat feeding of Hx mice increased serum cholesterol levels 2- to 3-fold. Serum triglycerides were reduced 50% in Hx mice; a further 30% reduction was seen after dietary cholesterol/fat. A serum marker for CYP7A1-mediated bile acid synthesis (C4) increased 2-fold in intact mice on cholesterol/fat diet. In Hx mice C4 levels were reduced by 50% as compared to intact controls, but were unexpectedly increased to levels seen in normal mice upon cholesterol/fat feeding. Hx of LDLRko mice moderately increased LDL-cholesterol and reduced triglycerides and GH treatment attenuated these effects; serum C4 levels were increased by GH treatment in all groups. In conclusion, mice can be used to explore the role of the pituitary in lipid metabolism. CYP7A1 is generally reduced in Hx mice but has a normal stimulatory response following dietary cholesterol suggesting that faulty regulation of CYP7A1 is not important for the reduced resistance to dietary cholesterol in Hx mice. Further, the LDLR is only to a minor part involved in the pituitary regulation of serum cholesterol in mice.
Matasconi
Manuela
M
Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine and Molecular Nutrition Unit, Center for Nutrition and Toxicology, NOVUM, Karolinska Institute, M63, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden.
Parini
Paolo
P
Angelin
Bo
B
Rudling
Mats
M
D000818:Animals; D002783:Cholestenones / Q000097:blood; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology; D003314:Corn Oil / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D019382:Human Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000502:physiology* / Q000601:surgery; D011973:Receptors, LDL / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D002783:Cholestenones; D002791:Cholesterol, Dietary; D008074:Lipoproteins; D011973:Receptors, LDL; D014280:Triglycerides; C030104:lipoprotein cholesterol; C030087:lipoprotein triglyceride; D019382:Human Growth Hormone; C002656:7 alpha-hydroxy-4-cholesten-3-one; D003314:Corn Oil; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; C502772:Cyp7a1 protein, mouse