Hormonal regulation of apolipoprotein AI

Abstract

Apolipoprotein AI (apo AI) is the major protein component of the serum high-density lipoprotein (HDL) particles. The antiatherogenic properties of apo AI alone or as part of HDL and their inverse correlation with the incidence of coronary heart disease underlie the clinical importance of the protein. A detailed understanding of the mechanisms by which apo AI is regulated will help us develop new and better ways to manipulate expression of the protein. Although there are many factors that influence apo AI expression, endogenous hormones are attractive because simple changes in abundance of these compounds will alter gene activity. Hormones belonging to the thyroid/steroid family that influence activity of the gene include thyroid hormone, glucocorticoids, gender-specific steroids and retinoic acid. Whereas thyroid, glucocorticoid and estradiol enhance activity of the gene, retinoic acid and androgens decrease it. The mechanisms that mediate the effects of the hormones include direct effects of the ligand and nuclear receptor complex on gene activity. However, indirect means involving the participation of transcription factors other than the hormone receptors are also possible. In summary, members of the same hormone family may have different mechanisms that mediate their activities on apo AI gene activity.