AGE-CHANGES IN THE ACTIVITY OF LIVER 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE IN FEMALE RATS - INFLUENCE OF MAMMARY PATHOLOGY

Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) reductase is a highly regul ated enzyme which shows a marked circadian rhythmicity. We studied the impact of aging on this rhythm as well as the degree of correlation b etween age changes in circulating pituitary hormone levels and liver r eductase activity in young (4 months) and old (33 months) Sprague-Dawl ey female rats. Lipid composition was also assessed in plasma and live r microsomes. The maximal activity (midnight) of HMG-CoA reductase fel l from 864 +/- 28 pmol mevalonate/min/mg protein in the young rats to 552 +/- 45 pmol/min/mg protein in the old animals, whereas significant change was not observed in the basal (noon) activity levels of the en zyme. Noon serum cholesterol, but not midnight values, was significant ly higher in the old rats. Liver cholesterol levels were similar in yo ung and old rats. In old rats, fatty acid composition of liver microso mes revealed an increase in linoleic acid concurrently with a signific ant decrease in arachidonic acid (AA). A significant correlation was n ot detected between the age changes in pituitary hormone (GH, PRL, TSH , FSH) serum levels and those in reductase activity. On the other hand , a significant positive correlation was found in the old rats between hepatic reductase activity and the severity of mammary pathology. We conclude that, like most biological rhythms, HMG-CoA reductase circadi an fluctuation decreases in amplitude with age. This change does not s eem to be linked to the alterations of neuroendocrine function associa ted with the aging process. The presence of growing mammary tumors see ms to stimulate liver reductase activity, which may constitute an adap tive response of the enzyme to cholesterol demand by the growing neopl astic tissue. (C) 1998 Elsevier Science Ireland Ltd.