Spermatic and peripheral venous plasma concentrations of dehydroepiandrosterone sulfate in prepubertal and pubertal boys

Dehydroepiandrosterone sulfate (DEAS), a major adrenal product, is quantitatively one of the most important steroids found in human testicular tissue. However, conflicting data have been reported about the testicular production of DEAS ‘in vivo’. We have measured the spermatic and peripheral concentrations of testosterone (T) and DEAS in two groups of prepubertal (Group I, N = 18) and pubertal (Group II; N = 11) boys undergoing surgery for undescended testis, inguinal hernia or varicocele. Mean (± SE) spermatic concentrations of DEAS (77 ± 16 and 113 ± 19 μg/dl in Group I and II respectively) were not significantly different from peripheral concentrations (70 ± 13 and 130 ± 16 μg/dl in Group I and II respectively). Mean spermatic concentrations of T (153 ± 101 and 7515 ± 4314 ng/dl in Group I and II respectively) were significantly different from peripheral concentrations (9 ± 1 and 149 ± 53 ng/dl; P < 0.001 in both groups). Spermatic and peripheral levels of T and DEAS found in prepubertal boys were significantly lower than those found in pubertal boys. Spermatic levels of DEAS were not significantly related with spermatic levels of T in both groups. Our data show that, as in adult subjects, no significant spermatic-peripheral DEAS gradient is present in prepubertal and pubertal boys.     

Effect of α-Lipoic Acid on Lipid Profile in Rats Fed a High-Fructose Diet

This study investigated the effect of administration of α-lipoic acid (LA) on lipid metabolism in high fructose–fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.     

青少年家族性高胆固醇血症患者血浆同型半胱氨酸和高敏C 反应蛋白水 平的临床价值及与血脂相关性研究

目的:探讨血浆同型半胱氨酸(Homocysteine,Hcy)、高敏C反应蛋白(Hypersensitive C-reactive protein,hs-CRP)在家族性高胆固醇血症(FH)的纯合子和杂合子患者中的水平及其与临床生化指标的相关性。方法:入选在2013.10~2015.7期间在动脉硬化门诊随访、确诊的家族性高胆固醇患者34人(纯合子14例,杂合子20例)。根据FH纯合子、杂合子、健康体检者分成三组,分别测定其总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(Glu)、Hcy、hs-CRP水平,并比较FH患者血浆LDL-C、非高密度脂蛋白(non-HDL)水平Hcy、hs-CRP水平的相关性。结果:FH组的TC、LDL-C、non-HDL、Hcy水平显著高于正常对照组(P0.05)。FH根据基因型亚组分析中,青少年纯合子组HDL-C[(0.78±0.21)vs(1.25±0.40)mmol/L]小于杂合子组(P0.001),而TC[(16.11±2.66)vs(7.30±2.54)mmol/L]、LDL-C[(14.06±2.22)vs(5.25±2.16)mmol/L]、non-HDL[(15.33±2.60)vs(6.05±2.61)mmol/L]、Hcy[(19.3±11.58)vs(11.29±3.42)μmol/L]水平显著高于杂合子组(P0.05)。Pearson相关性分析显示,FH患者血浆LDL-C、non-HDL水平与Hcy水平呈正相关(P0.05),而与hs-CRP无相关性。结论:FH患者,特别是青少年的纯合子患者,与对照组相较,具有较高的TC、LDL-C和Hcy水平,并且与血浆LDL-C、non-HDL水平呈正相关。FH患者hs-CRP的水平高于健康人,但差异无统计学意义,与血浆LDL-C、non-HDL水平也无明显相关性。     

Lipoprotein metabolism of pregnant women is associated with both their genetic polymorphisms and those of their newborn children

To explore whether the placenta contributes to the lipoprotein metabolism of pregnant women, we took advantage of the fact that placental proteins are encoded from the fetal genome and examined the associations between lipids of 525 pregnant women and the presence, in their newborns, of genetic polymorphisms of LPL and apolipoprotein E (APOE), two genes expressed in placenta. After adjustment for maternal polymorphisms, newborn LPL*S447X was associated with lower triglycerides (-21 +/- 9 mg/dl), lower LDL-cholesterol (LDL-C; -12 +/- 5 mg/dl), lower apoB (-14 +/- 4 mg/dl), higher HDL-C (5 +/- 2 mg/dl), and higher apoA-I (9 +/- 4 mg/dl) in their mothers; newborn LPL*N291S was associated with higher maternal triglycerides (114 +/- 31 mg/dl); and newborn APOE*E2 (compared to E3E3) was associated with higher maternal LDL-C (14 +/- 6 mg/dl) and higher maternal apoB (14 +/- 5 mg/dl). These associations (all P < 0.05) were independent of polymorphisms carried by the mothers and of lipid concentrations in newborns and were similar in amplitude to the associations between maternal polymorphisms and maternal lipids. Such findings support the active role of placental LPL and APOE in the metabolism of maternal lipoproteins and suggest that fetal genes may modulate the risk for problems related to maternal dyslipidemia (preeclampsia, pancreatitis, and future cardiovascular disease).     

Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII

Apolipoprotein CIII (apoCIII) has been implicated in hypertriglyceridemia and plasma apoCIII independently predicts risk for coronary heart disease. While hypertriglyceridemia in patients has been demonstrated to correlate with elevated plasma apoCIII levels and reduced lipoprotein lipase (LPL) activity, apoCIII transgenic mice show elevated LPL activity. In this study, we generated transgenic (Tg) rabbits expressing human apoCIII gene exclusively in liver and investigated the effect of apoCIII overexpression on lipid metabolism of rabbits. In comparison with non-Tg littermates, Tg rabbits had 3- and 3.2-fold increases in fed and fasted plasma triglycerides, respectively. In contrast, no significant differences were observed in plasma total cholesterol and high density lipoprotein cholesterol levels between Tg and non-Tg rabbits. Analysis of lipoprotein fractions revealed that elevated plasma triglyceride levels in Tg rabbits were mainly attributed to an increase in very low density lipoprotein/chylomicron-sized particles. Furthermore, Tg rabbits showed markedly delayed clearance of plasma triglycerides accompanied with significantly reduced LPL activity in post-heparin plasma compared to that in non-Tg controls. In conclusion, these results indicate apoCIII transgenic rabbits develop hypertriglyceridemia with similar mechanism in hypertriglyceridemic patients via delayed clearance of plasma triglycerides, and could be used as a valuable tool for the study of human hyperlipidemia in relation with atherosclerotic disorders.     

Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and hyperalphalipoproteinemia

To study the role of the two postheparin plasma lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) in high density lipoprotein (HDL) metabolism at a population level, we determined serum lipoproteins, apoproteins A-I, A-II, B, and E, and postheparin plasma LPL and HL activities in 65 subjects with a mean HDL-cholesterol of 34 mg/dl and in 62 subjects with a mean HDL-cholesterol of 87 mg/dl. These two groups represented the highest and lowest 1.4 percentile of a random sample consisting 4,970 subjects. The variation in HDL level was due to a 4.1-fold difference in the HDL2 cholesterol (P less than 0.001) whereas the HDL3 cholesterol level was increased only by 32% (P less than 0.001) in the group with high HDL-cholesterol. Serum apoA-levels were 128 +/- 2.2 mg/dl and 210 +/- 2.8 mg/dl (mean +/- SEM) in hypo- and hyper-HDL cholesterolemia, respectively. Serum apoA-II concentration was elevated by 28% (P less than 0.001) in hyperalphalipoproteinemia. The apoA-I/A-II ratio was elevated only in women with high HDL-cholesterol but not in men, suggesting that elevation of apoA-I is involved in hyperalphalipoproteinemia in females, whereas both apoA proteins are elevated in men with high HDL cholesterol. Serum concentration of apoE and its phenotype distribution were similar in the two groups. The HL activity was reduced in the high HDL-cholesterol group (21.2 +/- 1.5 vs. 38.5 +/- 1.8 mumol/h/ml, P less than 0.001), whereas the LPL activity was elevated in the group with high HDL-cholesterol compared to subjects with low HDL-cholesterol (27.8 +/- 1.3 vs. 19.9 +/- 0.8 mumol/h/ml, P less than 0.001). The HL and LPL activities correlated in opposing ways with the HDL2 cholesterol (r = 0.57, P less than 0.001 and r = 0.51, P less than 0.001, respectively), and this appeared to be independent of the relative ponderosity by multiple correlation analysis. The results demonstrate major influence of both HL and LPL on serum HDL cholesterol concentration at a population level.     

Pre-heparin plasma lipoprotein lipase mass: correlation with intra-abdominal visceral fat accumulation.

OBJECTIVE: To determine how lipoprotein lipase mass in the pre-heparin plasma is affected by body fat distribution, which is known to be closely related to lipid disorder, either directly or through insulin resistance. SUBJECTS: A total of 57 subjects consisting of 50 hyperlipidemic and 7 normolipidemic subjects (age 54 +/- IIy; 31 men, 26 women; body mass index 24+/- 2.5 kg/m2; serum total cholesterol 6.4+/-1.5 mmol/l; triglycerides, 2.4 +/- 1.7 mmol/l; HDL-cholesterol 1.3 +/- 0.5 mmol/l) were enrolled. MEASUREMENTS: We investigated the correlation between pre-heparin plasma LPL mass and intra-abdominal visceral fat area (or subcutaneous fat area) evaluated by computed tomography, and serum lipids and lipoproteins. RESULTS: Pre-heparin plasma LPL mass correlated inversely against intra-abdominal visceral fat area (r = - 0.51, p < 0.0001) and body mass index (r = - 0.46, p = 0.0003), but did not show any significant correlation with subcutaneous fat area. Pre-heparin plasma LPL mass had a positive correlation with serum high density lipoprotein cholesterol (r = 0.45, p = 0.0004) and a negative correlation against serum triglycerides (r = - 0.48, p = 0.0002). CONCLUSIONS: Pre-heparin plasma LPL mass is closely associated with intra-abdominal fat distribution, and the measurement of its value gives useful information concerning metabolic disorder.     

The effect of reduction of lipoprotein (a) on cellular cholesterol synthesis in non-diabetic and Type 2 diabetic subjects

This study investigates the effect of Lipoprotein (a) (Lp(a)) on cellular cholesterol synthesis in non-diabetic (n = 7) and Type 2 (non-insulin-dependent) diabetic subjects (n = 7) with elevated levels of Lp(a) (> 20 mg/dl). N-Acetylcysteine was used to lower Lp(a) in the control subjects and their lipoproteins were re-examined after 7 days of treatment. Low-density lipoprotein (LDL) was isolated and separated from Lp(a) by sequential ultracentrifugation. Regulation of cellular cholesterol synthesis was assessed by measuring incorporation of [¹⁴C]acetate into mononuclear leucocytes in the presence of LDL and Lp(a). Cellular cholesterol content was determined by a fluorometric assay. Delivery of cholesterol to the cell was examined using [³H]cholesteryl oleate-labelled LDL or Lp(a). LDL (5 μg/ml) from non-diabetic subjects suppressed cellular cholesterol synthesis by 66.2%, while Lp(a) at a similar concentration only suppressed cholesterol synthesis by 5.8% (P < 0.001). At a concentration of 20 μg/ml, Lp(a) suppressed cholesterol synthesis by 31.7%. The situation was similar in the diabetic subjects. Serum LDL cholesterol in non-diabetic subjects was 4.2 ± 0.5 mmol/1 and the LDL esterified/free cholesterol ratio was 2.6 ± 0.2. Following treatment with N-acetylcysteine, LDL cholesterol did not change, while Lp(a) decreased significantly by 24% (P < 0.05). The LDL esterified/free cholesterol ratio decreased to 2.2 ± 0.2 (P < 0.05) and there was a significant increase in the ability of the subjects LDL to inhibit cellular cholesterol synthesis (P < 0.05). There was a significant negative correlation between plasma Lp(a) and the ability of the patients' LDL to inhibit cellular cholesterol synthesis (r = − 0.68, P < 0.01). [³H]Cholesteryl-oleate-LDL (5 μg/ml) delivered 266 ± 13 ng cholesteryl oleate/mg cell protein, while it took 20 μg of [³H]cholesteryl oleate-labelled-Lp(a) to deliver a similar concentration (315 ± 21 ng cholesteryl oleate/mg cell protein). In conclusion it appears possible that the atherogenicity of Lp(a) may be associated with its effect on the LDL receptor which alters LDL receptor uptake, LDL composition and cellular cholesterol synthesis.     

Subchronic Arsenic Exposure Through Drinking Water Alters Lipid Profile and Electrolyte Status in Rats

Arsenic is a groundwater pollutant and can cause various cardiovascular disorders in the exposed population. The aim of the present study was to assess whether subchronic arsenic exposure through drinking water can induce vascular dysfunction associated with alteration in plasma electrolytes and lipid profile. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. On the 91st day, rats were sacrificed and blood was collected. Lipid profile and the levels of electrolytes (sodium, potassium, and chloride) were assessed in plasma. Arsenic reduced high-density lipoprotein cholesterol (HDL-C) and HDL-C/LDL-C ratio, but increased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and electrolytes. The results suggest that the arsenic-mediated dyslipidemia and electrolyte retention could be important mechanisms in the arsenic-induced vascular disorder.     

Metoclopramide,a dopamine antagonist,stimulates aldosterone secretion in rhesus monkeys but not in dogs or rabbits

This study was designed to investigate the role of dopamine in the control of aldosterone secretion in three frequently used laboratory animals. Five New Zealand rabbits, five mongrel dogs and five rhesus monkeys received metoclopramide (MCP) (200 μg/kg iv) and blood samples were collected at 0,5,15,30 and 45 minutes after drug administration. MCP had no effect on plasma aldosterone concentrations at any sampling time in the rabbits or dogs. However, MCP produced a rapid and marked increase in plasma aldosterone from 6.5±0.6 ng/dl to 18.1±2.8 ng/dl at 5 min. and a maximum level of 40.5±4.4 ng/dl at 10 min. after drug administration in the monkeys. MCP had no significant effect on plasma cortisol or plasma renin activity levels in the three species. Prolactin rose in the monkeys from 8.6±1.2 ng/ml to a maximum of 123.5±8.5 ng/ml at 15 min. after MCP. Administration of MCP resulted in a rise in plasma 18-hydroxycorticosterone in the monkeys from 12.5±1.4 ng/dl to a maximum concentration of 50.0±5.1 ng/dl 15 min. after drug administration. Plasma corticosterone, 11-deoxycorticosterone, and 18-hydroxydeoxycorticosterone were not altered by MCP. Although unlikely, it is possible that ketamine may have accounted for some of the changes in plasma aldosterone and 18-hydroxycorticosterone observed after metoclopramide in the monkeys. The findings suggest that dopamine modulates aldosterone biosynthesis in the monkey probably by regulating glomerulosa 18-hydroxylase activity.     

Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice.

Lipoprotein lipase (LPL) is known to play a crucial role in lipoprotein metabolism by hydrolyzing triglycerides; however its role in atherogenesis has yet to be determined. We have previously shown that low density lipoprotein receptor knockout mice overexpressing LPL are resistant to diet-induced atherosclerosis due to the suppression of remnant lipoproteins. Plasma lipoproteins and atherosclerosis of apolipoprotein (apo) E knockout mice which overexpress the human LPL transgene (LPL/APOEKO) were compared with those of control apoE knockout mice (APOEKO). On a normal chow diet, LPL/APOEKO mice showed marked suppression of the plasma triglyceride levels compared with APOEKO mice (54 vs. 182 mg/dl), but no significant changes in plasma cholesterol and apoB levels. Non-high density lipoproteins (HDL) from LPL/APOEKO mice had lower triglyceride content, a smaller size, and a more positive charge compared with those from APOEKO mice. Cholesterol, apoA-I, and apoA-IV were increased in HDL. Although both groups developed hypercholesterolemia to a comparable degree in response to an atherogenic diet, the LPL/APOEKO mice developed 2-fold smaller fatty streak lesions in the aortic sinus compared to the APOEKO mice. In conclusion, overproduction of LPL is protective against atherosclerosis even in the absence of apoE.     

Radioimmunoassay of androsterone and androsterone-3-sulfate in plasma

Details of a sensitive and specific radioimmunoassay for androsterone (1) and androsterone sulfate in plasma have been presented. Benzene extracts of plasma were chromatographed on a lumina to isolate the androsterone fraction either (a) directly after extraction (A) or (b) after solvolysis (AS). Following treatment with rabbit anti-A-17-BSA, antibody bound steroid was precipitated by ammonium sulfate. Androsterone concentrations in normal male plasma averaged 57 ± 24 (S.D.) ng/dl, range 35–135 ng/dl and for normal women, 44 ± 21 (S.D.) ng/dl, range 18–98 ng/dl. Androsterone sulfate concentrations were: males 55 ± 28 μg/dl (range 10–114 μg/dl); premenopausal females 52 ± 31 μg/dl (range 16–318 μg/dl).     

Possible Mechanism of Interleukin-2-Induced Decline of Serum Cholesterol During Adoptive Cellular Immunotherapy in Cancer Patients

The serum levels of total, LDL, and HDL cholesterol of patients receiving intravenous infusion of interleukin-2 as part of adoptive cellular immunotherapy were analyzed. The total, LDL, and HDL cholesterol significantly decreased to about one-half of the pretreatment levels after 5 days of infusion (183 ± 34 to 110 ± 19, 112 ± 40 to 48 ± 24, and 41 ± 10 to 16 ± 7 mg/dl, respectively). The decrease was gradual during each day of the treatment. Lymphocyte concentration increased markedly during treatment (4.0 ± 0.52 to 12.3 ± 2.95 million cells/ml) and the low-density lipoprotein receptor levels in the lymphocytes also increased significantly (1188 ± 240 to 1442 ± 276 ng of bound LDL/million cells). The decrease in cholesterol levels may be related to the cholesterol needed for membrane synthesis during lymphocyte proliferation.     

Beneficial effects of combined treatment with niacin and chromium on the liver of hyperlipemic rats

Many studies have shown that niacin and Cr exert combined effects. Significant beneficial effects in serum lipid levels following Cr supplementation have been reported. Niacin decreases total plasma levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol and increases high-density lipoprotein cholesterol. In this study, 12-mo-old female Swiss albino rats were used. They were randomly divided into four groups. The animals of group I (control) were fed with pellet chow. Group II was fed with pellet chow and treated with 250 μg/kg CrCl₃·6H₂O and 100 mg/kg niacin for 45 d, by the gavage technique. The rats of group III were fed with lipogenic diet consisting of 2% cholesterol 0.5% cholic acid, and 20% sunflower oil added to the pellet chow and given 3% alcoholic water for 60 d. Group IV was fed with the same lipogenic diet, and 15 d after, the experimental animals were made hyperlipemic; they were treated with 250 μg/kg CrCl₃·6H₂O and 100 mg/kg niacin by gavage technique for 45d. On d 60, liver and blood samples were taken from the animals. The sections were examined under light and electron microscopes. Serum total lipid and cholesterol levels were determined by spectrophotometric methods. The aim of the present study was *** DIRECT SUPPORT *** A02Q2015 00004     

Undaria pinnatifida soluble fiber regulates Angptl3-LPL pathway to lessen hyperlipidemia in mice

Angiopoietin-like protein 3 (Angptl3)–lipoprotein lipase (LPL) pathway may be a useful pharmacologic target for hyperlipidemia. The present study was conducted to test the effect of soluble fiber extracted from Undaria pinnatifida (UP), on hyperlipidemia in apolipoprotein E-deficient (ApoE^?/?) mice. Forty mice were divided into four groups (n?=?10): control group (C57BL/6J mice), ApoE^?/? mice group, and two groups of ApoE^?/? mice treated with UP fiber (5 or 10 % per day). UP soluble fiber treatment significantly decreased plasma and hepatic total cholesterol, triglycerides levels, plasma low-density lipoprotein cholesterol, and malondialdehyde concentrations and increased plasma high-density lipoprotein cholesterol level and downregulated protein expression of Angptl3 concomitantly with upregulated protein expression of LPL. In addition, T0901317 caused elevated expression of hepatic Angptl3 protein, and the effect of T0901317 was also abrogated by UP soluble fiber in C57BL/6J mice. The present results suggest that the UP soluble fiber regulates Angptl3-LPL pathway to lessen hyperlipidemia in mice.     

Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of TG-rich lipoproteins. To elucidate the physiological roles of LPL in lipid and lipoprotein metabolism, we generated transgenic rabbits expressing human LPL. In postheparinized plasma of transgenic rabbits, the human LPL protein levels were about 650 ng/ml, and LPL enzymatic activity was found at levels up to 4-fold greater than that in nontransgenic littermates. Increased LPL activity in transgenic rabbits was associated with as much as an 80% decrease in plasma triglycerides and a 59% decrease in high density lipoprotein-cholesterol. Analysis of the lipoprotein density fractions revealed that increased expression of the LPL transgene resulted in a remarkable reduction in the level of very low density lipoproteins as well as in the level of intermediate density lipoproteins. In addition, LDL cholesterol levels in transgenic rabbits were significantly increased. When transgenic rabbits were fed a cholesterol-rich diet, the development of hypercholesterolemia and aortic atherosclerosis was dramatically suppressed in transgenic rabbits. These results demonstrate that systemically increased LPL activity functions in the metabolism of all classes of lipoproteins, thereby playing a crucial role in plasma triglyceride hydrolysis and lipoprotein conversion, and that overexpression of LPL protects against diet-induced hypercholesterolemia and atherosclerosis.     

脂蛋白酯酶与动脉粥样硬化

脂蛋白酯酶(1ipopmtein lipase,LPL)是调节脂蛋白代谢的一种关键酶,如具有水解血浆脂蛋白中三酰甘油的作用等．体内LPL减少会导致血三酰甘油升高和高密度脂蛋白胆固醇降低,增加患动脉粥样硬化的危险．通过提高LPL的活性可以抑制动脉粥样硬化的发生发展．已有的研究说明NO-1886促进心肌和脂肪组织LPL mRNA表达,提高心肌、脂肪组织、骨骼肌和血液中LPL活性,因而改善脂蛋白代谢,抑制动脉粥样硬化．     

Cortisol and cortisone levels in umbilical cord plasma and maternal plasma of normal pregnancies

A method for assaying cortisol and cortisone using chromatography on either paper or Sephadex LH-20 columns for isolation, followed by competitive protein binding, has been applied to umbilical cord and maternal plasma samples. In mixed cord plasma the mean cortisol concentration was 6.0 ± 0.8 μg/100 ml (n = 9) and the mean cortisone concentration was 13.5 ± 2.9 μg/100 ml (n = 9). In cord arterial plasma the mean cortisol concentration was 6.3 ± 2.9 μg/100 ml (n = 6) and the mean cortisone level was 10.1 ± 2.5 μg/100 ml (n = 6). For cord venous plasma, the mean level of cortisol was 5.6 ± 1.5 μg/100 ml (n = 6) and of cortisone was 13.5 ± 2.4 μg/100 ml (n = 6). Maternal plasma gave a mean value of cortisol of 42.3 ± 4.5 μg/100 ml (n = 6) and of cortisone of 6.2 ± 0.9 μg/100 ml. The results of this study suggest that the fetus at term-gestation produces cortisol. The significance of this production compared with placental transfer of maternal cortisol into the fetal circulation however is uncertain.     

Tamoxifen inhibits lipoprotein activity: in vivo and in vitro studies

Tamoxifen, a nonsteroidal antiestrogenic antitumor agent, has weak estrogen-like effects on lipid metabolism, however, the mechanism remains unknown. We previously reported that tamoxifen decreases the activity of lipoprotein lipase (LPL), a key enzyme in triglyceride metabolism, in patients with breast cancer. This study evaluated the effect of tamoxifen on LPL activity in vitro and in vivo. In experiment 1, total cholesterol, triglyceride, adipose tissue weight, and LPL activity of post-heparin plasma were measured in ovariectomized female rats with and without tamoxifen treatment. In experiment 2, purified very-low-density lipoprotein (VLDL) and purified LPL were incubated with and without tamoxifen or estrogen, and the triglycerides in VLDL were measured using an enzymatic method. In experiment 1, total cholesterol and adipose tissue weight decreased significantly in tamoxifen-treated rats (p < 0.001 and p < 0.01, respectively). Triglyceride measurements were not significantly different between the two groups, however, the LPL activity was lower in tamoxifen-treated rats (p < 0.005). In experiment 2, triglycerides in VLDL were significantly higher after VLDL and LPL were incubated with tamoxifen and estrogen (p < 0.005). We concluded that tamoxifen inhibits the hydrolytic activity of LPL in vivo and in vitro. This mechanism may explain the elevated serum triglyceride levels in some patients treated with tamoxifen.     

Plasma lipoprotein cholesterol concentrations in the golden-mantled ground squirrel (Spermophilus lateralis): a comparison between pre-hibernators and hibernators.

1. The concentrations of total cholesterol (free cholesterol plus cholesteryl ester) in the plasma and in two lipoprotein fractions of golden-mantled ground squirrels (Spermophilus lateralis) were measured during pre-hibernation and compared to those values measured during hibernation. 2. Hibernating ground squirrels had significantly higher (P less than 0.005) very low density lipoprotein plus low density lipoprotein cholesterol (VLDL + LDL-C) concentrations than did pre-hibernating ground squirrels. 3. Hibernating squirrels additionally exhibited significantly higher (P less than 0.005) total plasma cholesterol concentration per high density lipoprotein cholesterol concentration (TPC/HDL-C) ratios than did pre-hibernating squirrels. 4. The significant differences in the lipoprotein cholesterol concentrations observed in this study suggest that lipoprotein metabolism in pre-hibernators was significantly different from that in hibernators and was a reflection of the marked biochemical and physiological adjustments these animals must undergo during their transition from pre-hibernation to hibernation.