Increased mRNA for low density lipoprotein receptor in livers of rabbits treated with 17 alpha-ethinyl estradiol.

Patrick, T. S.; Yamamoto, Tokuo; Goldstein, Joseph L.; Brown, Michael S.

doi:10.1073/pnas.83.3.792

Cited by 181 publications

(69 citation statements)

References 29 publications

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“…It has been shown that induction of hepatic LDL-R activity is the major mechanism responsible for the hypocholesterolemic effects of estrogen (38,39). In rats, estrogen induces expression of hepatic LDL-R (40).…”

Section: Discussionmentioning

confidence: 99%

Retrograded Tapioca Starch Prevents Ovarian Hormone Deficiency-Induced Hypercholesterolemia

Liu

Sawauchi

Ogawa

et al. 2006

J Nutr Sci Vitaminol

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SummaryThe purpose of this study was to examine whether retrograded tapioca starch (RS3-tapioca) prevents ovarian hormone deficiency-induced hypercholesterolemia. Sixmonth-old Wistar female rats were subjected to sham-operation or ovariectomy, and fed a cholesterol-free purified diet with or without RS3-tapioca (150 g/kg diet) instead of digestible cornstarch for 28 d. Body weight gain and food intake increased in ovariectomized rats (OVX-rats). Plasma total cholesterol concentration was lowered by RS3-tapioca in OVX rats, but not in sham-operated rats. Liver lipids increased in OVX-rats, but liver cholesterol concentration was not affected by ovariectomy and RS3-tapioca. CYP7A1 activity, small intestinal and cecal bile acid content, and fecal bile acid excretion were increased by RS3-tapioca. The ratio of cholic acid groups to chenodeoxycholic acid groups in the bile acid of the small intestine was increased by RS3-tapioca. Thus, the preventive effect of RS3-tapioca on the ovarian hormone deficiency-associated increase in plasma cholesterol concentration appears to be mediated by accelerated fecal excretion of bile acid and an increase in the intestinal pool of bile acid. Key Words retrograded tapioca starch (RS3-tapioca), ovariectomized rats, plasma cholesterol Resistant starch (RS) is, by definition, the sum of starch and the products of starch degradation not absorbed in the small intestine of healthy individuals ( 1 ). RS is now organized into four categories: physically inaccessible starch (RS1), resistant granules and high amylose starches (RS2), retrograded starches (RS3) and chemically modified starches (RS4) ( 2 ). RS appears to have various physiological effects, such as a decrease in postprandial glycemic and insulinemic responses, reduction of plasma cholesterol and triglyceride concentrations, an improvement in whole body insulin sensitivity, an increase in satiety, and a reduction in fat storage ( 3 ).Menopause, whether natural or surgically induced, is associated with elevated concentrations of circulating total cholesterol and low-density lipoprotein-cholesterol, Placing postmenopausal women at greater risk of coronary heart disease (CHD) ( 4 -7 ). Estrogen replacement therapy (ERT) in postmenopausal women reduces the risk of CHD, in part, by modulating plasma cholesterol; however ERT and cholesterol-lowering pharmacological agents may have side effects.Starch consists of a mixture of two polymers, amylose and amylopectin. Different starches have different relative ratios of amylose and amylopectin. The properties of a starch are highly influenced by the structure of its components. The different properties depend on the crystalline ultra-structure, which differs according to the origin of the starch. X-ray diffraction has been used to characterize the crystalline/amorphous nature of starches. The X-ray diffraction pattern of tapioca starch is C type, while that of corn, potato and rice starch is A, B and A type, respectively. The physical and chemical properties of RS3-tapioca may differ from t...

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Section: Discussionmentioning

confidence: 99%

Retrograded Tapioca Starch Prevents Ovarian Hormone Deficiency-Induced Hypercholesterolemia

Liu

Sawauchi

Ogawa

et al. 2006

J Nutr Sci Vitaminol

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“…Because estrogens also affect the production of lipoproteins, we also examined the regulation of apoAI and apoB production in both species to ascertain whether any rat/mouse differences in the responses of the LDL-receptor were also applicable to apoA1 and apoB. In rats, both 17u-ethinyl estradiol and 17p-estradiol produced an almost complete disappearance of all lipoproteins from plasma [5,11,121. However, in mice, estradiol produced 2-fold increases in plasma apoB while drops in HDL-cholesterol and apoAI levels were relatively small (Tables 1 and 2, Fig.…”

Section: Discussionmentioning

confidence: 99%

In vivo regulation of low‐density lipoprotein receptors by estrogen differs at the post‐transcriptional level in rat and mouse

Srivastava

Baumann

Schonfeld

1993

European Journal of Biochemistry

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Rats and mice are frequently used in studies of the regulation of lipoprotein metabolism. Although the species are closely related, they differ dramatically in the responses of their lipoproteins to estrogen administration. In rats, estrogens produce profound decreases in the levels of all plasma lipoproteins and this is attributed largely to estrogen-induced increases of hepatic low-density lipoprotein receptor (LDL-receptor) activity. Estrogens affect mouse plasma lipoproteins to a much lesser extent. Therefore, one of our aims was to compare the regulation of LDL-receptor gene expression in rats and mice at several potential loci of regulation. To assess the specificity of the estrogen effect, we also compared the responses of apolipoprotein A1 (apoAI), apolipoprotein B (apoB), and /3-actin to the response of the LDL-receptor. In male Sprague Dawley rats given 1 7 8 estradiol or 17a-ethinyl estradiol at supraphysiological doses of 5 pg/g body masdday, plasma total cholesterol and triacylglycerols fell to = 5% and = 50%, and, plasma apoAI and apoB fell to = 12% and ~1 6 % of controls, respectively. By contrast, in male C3H/HeJ mice the above parameters dropped only to ~6 5 % of controls and apoB concentrations rose to ~2 0 0 % of controls. In rats, relative rates of LDL-receptor mRNA transcription (nuclear 'run-off' assay) and total hepatic, nuclear and polysomal LDL-receptor mRNA levels (RNase protection assay) increased by 1.5 -2-fold, while synthesis of LDL-receptor protein on hepatic polysomes (in a wheat-germ translation system) increased 8-fold and LDL-receptor protein mass in hepatic plasma membranes increased 10-fold (by immunoblotting). In mouse liver, too, LDL-receptor mRNA levels increased 1.5-fold and the LDL-receptor mRNA transcription start sites in rat and mouse were found to be the same, but mouse LDL-receptor protein mass did not change, i.e. LDL-receptors of mice were similar to rat with respect to transcriptional regulation, but differed in their post-transcriptional control mechanisms.In rats, estrogen administration increased apoAI inRNA transcription rates 1.6-fold and also apoAI mRNA levels in total liver homogenates, nuclei and polysomes, (2-fold for each) consistent with transcriptional regulation. However, apoAI synthesis on total RNA increased less than apoAI mRNA, indicating that apoAI translational control mechanisms, at least in part, also regulate hepatic rates of apoAI production. ApoB mRNA transcription rates and levels showed small increases following estrogen administration. Hepatic p-actin mRNA transcription and levels did not change. These changes in apoAI and apoB in rats were similar to those previously reported for mice, i.e. estrogen regulates apoAI and apoB gene expression both at the transcriptional and translational levels with rats and mice responding similarly. Thus, in rat liver, estrogen upregulates LDL-receptor production by transcriptional and even more so by translational mechanisms while mouse LDLreceptor remains unchanged. These interspecies differences in t...

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“…To investigate this possibility, several hypolipidemic agents, such as cholestyramine [10] and 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors [1 1, 12], which induce LDL receptor expression, have been used to lower serum Lp(a), but most of these attempts have failed to demonstrate any reduction. The only exception is estrogen, a hormone which elevates LDL receptors and reduces LDL-cholesterol [13,14]. Very recently, we observed a marked reduction in serum Lp(a) in a patient with familial hypercholesterolemia (FH) following estrogen therapy for prostatic cancer [15].…”

Section: Lipoproteinmentioning

confidence: 95%

“…Although the exact mechanism of estrogen's action was unknown, we previously proposed [15] that enhanced Lp(a) removal via LDL receptors might be responsible for the reduction in serum Lp(a), because the reduction in serum Lp(a) occurred in parallel with that of LDL-cholesterol, and estrogen is known to cause a significant decrease in LDL by increasing LDL-receptor expression, and hence LDL uptake in the liver [13,14]. Certainly the LDL receptor is a possible candidate, but our recent observations [24] as well as those of others [10][11][12], indicate that intervention trials with hypolipidemic agents, such as cholestyramine and HMG CoA reductase inhibitors, which induce LDL-receptor expression, do not cause a reduction in serum Lp(a), while estrogen does.…”

Section: Statistical Analysis Serum Lp(a)mentioning

confidence: 99%

Reduction of Serum Lipoprotein (a) by Estrogen in Men with Prostatic Cancer.

1993

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Abstract. The catabolism of lipoprotein(a), Lp(a), remains unclear. Very recently we observed that estrogen, a hormone known to increase low-density lipoprotein (LDL) receptor activity, reduced serum Lp(a) levels in a man with familial hypercholesterolemia (FH) (JAMA 267: 2328(JAMA 267: , 1992. In the present study, we attempted to further evaluate this Lp(a)-lowering action of estrogen in men without FH. Seven men, aged 61-84 yr, treated with estrogen for prostatic cancer were the subjects and seven men who underwent surgical treatment without estrogen therapy served as controls. Fasting blood was collected before and 1-3 months after estrogen therapy, and serum Lp(a) levels and lipoprotein profiles were determined. Estrogen treatment caused significant changes in serum lipoproteins, i.e., decreases in LDL-cholesterol, and increases in high-density lipoprotein (HDL)-cholesterol. Serum triglyceride levels tended to increase. Serum apo A-1 underwent a two-fold increase, while apo B did not change. Serum Lp(a) levels ranged from 8 to 62 mg/dl. After estrogen treatment serum Lp(a) was reduced markedly, with a mean reduction of 81% (71-95%). Serum lipids, lipoproteins and Lp(a) did not change significantly in the controls. The results demonstrated a regulating effect of estrogen on serum Lp(a) levels, and the findings further suggested that Lp(a) is removed via LDL receptors. However, previous studies have shown that maneuvers causing a decrease in LDL-cholesterol do not always cause a reduction in serum Lp(a). Thus, our findings suggested the possible presence of a receptor which is estrogen-inducible and different from the LDL receptor. [6, 7] and cerebral arteries [8]. Moreover, the serum Lp(a) level is an indicator of the presence and severity of coronary artery disease [9]. Because of its clinical significance, it is very important to evaluate attempts to lower the serum Lp(a) concentration in vivo. The serum Lp(a) concentration is the result of a balance between synthesis and elimination. Lp(a) is mostly synthesized in the liver, however, the site of catabolism of Lp(a) remains unknown [2]. The LDL-receptor is a candidate for Lp(a) removal from the circulation. To investigate this possibility, several hypolipidemic agents, such as cholestyramine [10] and 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors [1 1, 12], which induce LDL receptor expression, have been used to lower

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Increased mRNA for low density lipoprotein receptor in livers of rabbits treated with 17 alpha-ethinyl estradiol.

Cited by 181 publications

References 29 publications

Retrograded Tapioca Starch Prevents Ovarian Hormone Deficiency-Induced Hypercholesterolemia

Retrograded Tapioca Starch Prevents Ovarian Hormone Deficiency-Induced Hypercholesterolemia

In vivo regulation of low‐density lipoprotein receptors by estrogen differs at the post‐transcriptional level in rat and mouse

Reduction of Serum Lipoprotein (a) by Estrogen in Men with Prostatic Cancer.

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