NDLI: Lymphosarcoma-induced alterations in hepatic adrenergic receptors: Implications to the hypoglycemia of cancer cachexia

Content Provider	Springer Nature Link
Author	Hemmings, Susan J. Wilson, Thomas R.
Copyright Year	2003
Abstract	A highly malignant transplantable rat lymphosarcoma was studied to determine the involvement of hepatic adrenergic receptors in the development of the hypoglycemia of cancer cachexia. Following inoculation of Fischer 344 rats with lymphosarcoma cells, rats were examined at 2 and 4 weeks, at the pre-cachexic stage; 6 weeks, at the transitional stage; and 7 weeks, at the cachexic hypoglycemic stage of lymphosarcoma progression. Death occurred by the 8th week. Blood glucose levels in lymphosarcoma-bearing rats relative to control rats were: unaffected at week 2; significantly reduced 8% at weeks 4 and 6; and reduced 24% at week 7. α$_{1}$ adrenergic receptor binding to plasma membranes isolated from the livers of lymphosarcoma-bearing rats was: 114, 89, 67 and 30% of control at weeks 2, 4, 6, and 7, respectively. Kinetic analysis indicated that the lymphosarcoma-induced decrease at week 7 was due to a decrease in numbers of receptors with no change in affinity: Bmax$_{control}$: 1411.1 fmol/mg; Kd$_{control}$: 0.44 nm; Bmax$_{lympho}$: 345.5 fmol/mg; Kd$_{lympho}$: 0.50 nm. α$_{2}$ adrenergic receptor binding to plasma membranes isolated from the livers of lymphosarcoma-bearing rats was: 130, 137, 243 and 212% of control at weeks 2, 4, 6, and 7, respectively. The pattern of changes in hepatic α$_{1}$, α$_{2}$ and β adrenergic receptors at week 6 was comparable to that of 17 day fetal liver: a decrease in α$_{1}$ and β and an increase in α$_{2}$. Hepatic adrenergic receptor changes occurred in the absence of liver damage and were not due to contamination of the liver plasma membrane fractions with lymphosarcoma cells. Plasma insulin levels displayed modest (10–15%), but not statistically significant, increases post-inoculation after week 4. Plasma glucagon levels fluctuated post-inoculation until week 7 where they were significantly increased: 202% of control. Plasma T$_{3}$ and T$_{4}$ levels displayed an early and steady decline after lymphosarcoma inoculation: T$_{3}$: unchanged at week 2 and significantly decreased 14, 44 and 50% at weeks 4, 6 and 7, respectively. T$_{4}$ increased 20% at week 1; decreased 9% at week 4 and significantly decreased thereafter: 55 and 49% at weeks 6 and 7, respectively. We propose that the development of the hypoglycemia of cancer cachexia in this lymphosarcoma model is due primarily to an early and progressive thyroid hormone dependent decrease in the number of hepatic α$_{1}$ adrenergic receptors, compounded by an increase and decrease, respectively, in the hepatic β and α$_{2}$ adrenergic receptors.
Starting Page	167
Ending Page	177
Page Count	11
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	250
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2003-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cardiology Medical Biochemistry Oncology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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