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Abstract

We have shown mouse to be an useful animal model for studies on the estrogen-mediated synthesis and secretion of lipoproteins since, unlike in rats, low density lipoprotein receptors are not upregulated in mice. This results into the elevation of plasma levels of apolipoprotein (apo) B and apoE, and lowering of apoA-1-containing particles. The mechanisms of apoB and apoE elevation by estrogen have been elucidated, but the mechanism of lowering of plasma levels of HDL is still not known. Among other factors, apoA-I, cholesterol ester transfer protein (CETP), scavenger receptor B1 (SR-B1), and hepatic lipase are potential candidates that modulate plasma levels of HDL. Since estrogen treatment increased hepatic apoA-I mRNA and apoA-I synthesis, and mouse express undetectable levels of CETP, we tested the hypothesis that estradiol-mediated lowering of HDL in mice may occur through modulation of hepatic lipase (HL). Four mouse strains (C57L, C57BL, BALB, C3H) were administered supraphysiological doses of estradiol, and plasma levels of HDL as well as HL mRNA were quantitated. In all 4 strains estradiol decreased plasma levels of HDL by 30%, and increased HL mRNA 2-3 fold. In a separate experiment groups of male C57BL mouse were castrated or sham-operated, and low and high doses of estradiol administered. We found 1.4-2.5 fold elevation of HL mRNA with concomitant lowering of HDL levels. Ten other mouse strains examined also showed estradiol-induced elevation of HL mRNA, but the extent of elevation was found to be strain-specific. Based on these studies, we conclude that hepatic lipase is an important determinant of plasma levels of HDL and that HL mRNA is modulated by estrogen which in turn may participate in the lowering of plasma levels of HDL.

Lipid Complications after Hematopoietic Stem Cell Transplantation (HSCT) in Pediatric Patients

“…Hepatic lipase in the liver-associated enzyme is responsible for the differences in HDL content between both genders [22]. The hydrolytic enzyme's expression remains under the control of estrogens [23,24]. Therefore, in female patients, the conversion of HDL3 to HDL2 is elevated [23].…”

Sex steroids mediate discrete effects on HDL cholesterol efflux capacity and particle concentration in healthy men

“…The opposing effects of testosterone and estradiol on large HDL particles may also explain the variable findings from past studies that have examined changes in HDL particle size consequent to testosterone replacement therapy. 42,43 Both testosterone and estradiol play roles in the regulation of hepatic lipase, 43,44 an effect that may prove a key mechanism whereby sex steroids contribute to the remodeling of HDL particles. Testosterone and estrogen also have been implicated in the regulation of SR-BI expression 45,46 and therefore could influence hepatic uptake of HDL-associated cholesterol as well as HDL remodeling.…”

Lifestage Sex-Specific Genetic Effects on Metabolic Disorders in an Adult Population in Korea: The Korean Genome and Epidemiology Study

“…The genetic polymorphisms of the SEC16B gene region showed significant associations with obesity; SEC16B is a well-known obesity-related genetic variant [ 24 ]. SEC16B is also a gene region associated with age at menarche and other reproductive traits [ 25 , 26 ]. Thus, given that SEC16B is related to female reproductive function, the association between this locus and general obesity later life in women may be explainable.…”