Age-related changes in the responsiveness of apolipoprotein a1 to
thyroid hormone.
Mooradian, Arshag D., Norman C. W. Wong, Gul N. Shah.
St. Louis V.A. Medical Center and the Division of Endocrinology,
Department of Internal Medicine, St. Louis University School of
Medicine, St. Louis, MO and from the Department of Medicine and
Medical Biochemistry University of Calgary, Calgary, Alberta
APStracts 3:0230R, 1996.
To determine the age-related changes in the effect of thyroid hormone
on ApoA1 gene expression, male Fischer 344 rats at 4 (young), and 26
(aged) months of age were studied. Hyperthyroidism was induced with
daily intraperitoneal injections of L-triiodothyronine (15 _g/100)
for 10 days. Hypothyroidism was induced with 0.025% methimazole in
drinking water for 4 weeks. Hyperthyroidism was associated with
increases serum ApoA1 levels in young rats (7.52 +/- 0.41 O.D. vs.
3.67 +/-0.30 O.D.; p<0.01). The increase in aged rats (6.5 +/-
0.87 O.D. vs. 5.14 +/- 0.09 O.D.) did not reach statistical
significance. Hypothyroidism was not associated with significant
changes in serum ApoA1 levels in either young or aged rats.
Hyperthyroidism was associated with 2.5 fold increase in ApoA1 mRNA
in young rats and 1.7 fold increase in aged rats. Hypothyroidism was
associated with 3.6 fold reduction in ApoA1 mRNA in young rats but
there was no significant change in aged hypothyroid rats. Mobility
shift assays indicated that the binding of transacting factors to
ApoA1 promoter increased in hyperthyroid young rats but not in
hyperthyroid aged rats. It is concluded that aging in rats is
associated with reduced ApoA1 responsiveness to thyroid hormones.
This altered responsiveness could partly be the result of changes in
the binding activity of nuclear factors to the ApoA1 promoter.
Received 26 February 1996; accepted in final form 6 June 1996.
APS Manuscript Number R112-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96