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.

Serum Lipid Alterations in Early Rheumatoid Arthritis Patients on Disease Modifying Anti Rheumatoid Therapy

“…In another study by Peters et al [24] on 80 RA patients on infliximab and corticosteroids, all the lipids were at baseline levels after 48 weeks of treatment while Apo A-1 levels increased and remained elevated at 48 weeks. Glucocorticoids have been shown to induce Apo A-1 promoter activity and gene expression through proximal promoter elements situated between nucleotides -235 and -144 [25]. Thus, the increase in Apo A-1 levels found in the treatment group in our study may be explained as the effect of glucocorticoids administered to these patients.…”

HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (−629C>A) and modified by glucocorticoid treatment

“…Notably, it is likely that other mechanisms also contribute to the effects of glucocorticoids on HDL metabolism. Glucocorticoids increase hepatic synthesis of apolipoprotein A-I, the major HDL protein constituent (39,40), and reduce hepatic lipase activity (41), thereby maintaining or even increasing HDL-C. Several interdependent metabolic processes may, therefore, be involved in an effect modification of concomitant glucocorticoid treatment on the HDL-C response to GH replacement.…”

Genome-wide search for QTLs for apolipoprotein A-I level in elderly Swedish DZ twins: evidence of female-specific locus on 15q11–13

“…26 Thus, it is not surprising to observe QTLs that differ between the sexes. The most striking signal observed in this study is a female-limited QTL in the 15q11 -13 region.…”