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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.
Mol Cell Biochem 2001 Sep
PMID:Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats. 1171 52

Evidence has been accumulated that 7-hydroxyepimers of dehydroepiandrosterone (7-OH-DHEA), may act as locally active immunomodulatory and immunoprotective agents, counteracting exaggerated actions of glucocorticoids. Since Skinner et al. (1977) developed the first unspecific RIA, it has been known that 7alpha-OH-DHEA is present in near nanomolar concentration in human blood. No data have been available, however, on its changes during the human life. Using recently developed specific radioimmunoassays for determination of both 7-OH-DHEA epimers, 7alpha- and 7beta-OH-DHEA were measured in sera from 252 males and 172 females, representing age groups from 10 to 91 years (males) and from 10 to 72 years (females). The dependence of 7-OH-DHEA levels on age was evaluated by using polynomial fitting of the 4th or 5th degree. In contrast to men, where a distinct decline with age occurred, two local maxima have been recorded round the age 22 and 53, respectively, in females. The curves of age dependence of 7-OH-DHEA levels in both sexes resembled those of previously determined unconjugated DHEA, but in the latter case the second maximum in women was found about 10 years earlier than 7-OH-DHEA, in a premenopausal period. The levels of both 7-OH-DHEA epimers correlated excellently with each other.
J Steroid Biochem Mol Biol 2001 Oct
PMID:7-Hydroxydehydroepiandrosterone epimers in the life span. 1171 7

The effect of dietary lipid on the fatty acid composition of muscle, testis and ovary of cultured sweet smelt, Plecoglossus altivelis, was investigated and compared with that of wild sweet smelt. Cultured fish were fed three different diets for 12 weeks: a control diet rich in docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) (CO group); a diet deficient in DHA and EPA (DP group); and a diet rich in alpha-linolenic acid (ALA, 18:3n-3), but deficient in DHA and EPA (LP group). The fatty acid composition of muscle and gonad lipids was related with dietary fatty acids. Despite the difference in DHA and EPA content in the diets, muscles and gonads, respectively, contained almost equal levels of DHA and EPA in each CO and DP group. However, the muscle and gonad of the LP group showed a lower level of DHA than other groups, due to having the highest level of ALA. In the wild fish muscle, the DHA content was similar to that of CO and DP groups, but the EPA content showed the highest level in all groups. There was no difference in the muscle fatty acid proportions between male and female. On the other hand, the testes of cultured and wild fish were rich in DHA, EPA, docosapentaenoic acid and arachidonic acid, while ovaries were rich in oleic, palmitoleic, linoleic acids and ALA. Moreover, of all the groups, the fish fatty acid composition of the LP group was closest to that of wild fish. These results indicate that in the sweet smelt, tissue n-3 polyunsaturated fatty acids (PUFAs) greater than C20 can be synthesized from dietary precursors and special fatty acids are preferentially accumulated to the testis or ovary, respectively, to play different physiological functions.
Comp Biochem Physiol B Biochem Mol Biol 2002 Feb
PMID:Preferential accumulation of fatty acids in the testis and ovary of cultured and wild sweet smelt Plecoglossus altivelis. 1181 46

Dehydroepiandrosterone (DHEA) can function to protect neural precursors and their progeny targeted with toxic insults; however, the molecular mechanisms underlying the neuroprotective effects of DHEA are not understood. We cultured neural precursors from the embryonic forebrain of rats and examined the effects of DHEA and its sulfated derivative (DHEAS) on the activation of the serine-threonine protein kinase Akt, which is widely implicated in cell survival signaling. We found that DHEA activated Akt in neural precursor culture, in association with a decrease in apoptosis. In contrast, DHEAS decreased activated Akt levels and increased apoptosis. The effects of DHEA on neural cell survival and activation of Akt were not blocked by the steroid hormone antagonists flutamide and tamoxifen, but both were blocked by a PI3-K inhibitor, LY294002. These findings suggest that during neurogenesis in the developing cortex, DHEA and DHEAS regulate the survival of neural precursors and progeny through the Akt signaling pathway.
Brain Res Mol Brain Res 2002 Jan 31
PMID:Dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) regulate apoptosis during neurogenesis by triggering the Akt signaling pathway in opposing ways. 1183 96

Antarctic euphausiids, Euphausia superba, E. tricantha, E. frigida and Thysanoessa macrura were collected near Elephant/ Island / during 1997 and 1998. Total lipid was highest in E. superba small juveniles (16 mg g(-1) wet mass), ranging from 12 to 15 mg in other euphausiids. Polar lipid (56-81% of total lipid) and triacylglycerol (12-38%) were the major lipids with wax esters (6%) only present in E. tricantha. Cholesterol was the major sterol (80-100% of total sterols) with desmosterol second in abundance (1-18%). 1997 T. macrura and E. superba contained a more diverse sterol profile, including 24-nordehydrocholesterol (0.1-1.7%), trans-dehydrocholesterol (1.1-1.5%), brassicasterol (0.5-1.7%), 24-methylenecholesterol (0.1-0.4%) and two stanols (0.1-0.2%). Monounsaturated fatty acids included primarily 18:1(n-9)c (7-21%), 18:1(n-7)c (3-13%) and 16:1(n-7)c (2-7%). The main saturated fatty acids in krill were 16:0 (18-29%), 14:0 (2-15%) and 18:0 (1-13%). Highest eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)] occurred in E. superba (EPA, 15-21%; DHA, 9-14%), and were less abundant in other krill. E. superba is a good source of EPA and DHA for consideration of direct or indirect use as a food item for human consumption. Lower levels of 18:4(n-3) in E. tricantha, E. frigida and T. macrura (0.4-0.7% of total fatty acids) are more consistent with a carnivorous or omnivorous diet as compared with herbivorous E. superba (3.7-9.4%). The polyunsaturated fatty acid (PUFA) 18:5(n-3) and the very-long chain (VLC-PUFA), C(26) and C(28) PUFA, were not present in 1997 samples, but were detected at low levels in most 1998 euphausiids. Interannual differences in these biomarkers suggest greater importance of dinoflagellates or some other phytoplankton group in the Elephant Island area during 1998. The data have enabled between year comparisons of trophodynamic interactions of krill collected in the Elephant Island region, and will be of use to groups using signature lipid methodology.
Comp Biochem Physiol B Biochem Mol Biol 2002 Apr
PMID:Interannual and between species comparison of the lipids, fatty acids and sterols of Antarctic krill from the US AMLR Elephant Island survey area. 1192 86

Inhibitory effects of flavonoid phytochemicals, flavones, flavonols and isoflavones on cortisol production were examined in human adrenal H295R cells stimulated with di-buthylyl cAMP. In addition, the inhibitory effects of these chemicals on the activity of P450scc, 3beta-HSD type II (3beta-HSD II), P450c17, P450c21 and P45011beta, steroidogenic enzymes involved in cortisol biosynthesis, were examined in the same cells. Exposure to 12.5 microM of the flavonoids 6-hydroxyflavone, 4'-hydroxyflavone, apigenin, daidzein, genistein and formononetin significantly decreased cortisol production (by 6.3, 69.6, 47.5, 26.6, 13.8 and 11.3%, respectively), and biochanin A significantly decreased cortisol production (by 47.3%) at a concentration of 25 microM without any significant cytotoxic effects or changes in cell number. Daidzin, the 7-glucoside of daidzein, did not alter cortisol production by H295R cells at concentrations over 10 microg/ml (24 microM). Daidzein-induced reduction of cortisol production by H295R cells was not inhibited by the estrogen receptor antagonist ICI 182,780. The flavonoids 6-hydroxyflavone, daidzein, genistein, biochanin A and formononetin strongly and significantly inhibited microsomal 3beta-HSD II activity at concentrations from 1 to 25 microM, and I(50) values were estimated to be 1.3, 2, 1, 0.5 and 2.7 microM, respectively. In addition, these flavonoids significantly inhibited microsomal P450c21 activity at 12.5 and/or 25 microM. In addition, 6-hydroxyflavone inhibited activity of microsomal P450c17 and mitochondrial P45011beta at 12.5 and/or 25 microM. Results of Lineweaver-Burk's plot analysis indicate that daidzein is a competitive inhibitor of the activity of 3beta-HSD II and P450c21. K(m) and V(max) values of 3beta-HSD II for DHEA were estimated to be 6.6 microM and 328pmol/minmg protein, respectively. K(m) and V(max) values of P450c21 for progesterone were estimated to be 2.8 microM and 16pmol/minmg protein, respectively. K(i) values of 3beta-HSD II and P450c21 for daidzein were estimated to be 2.9 and 33.3 microM, respectively.
J Steroid Biochem Mol Biol 2002 Mar
PMID:Effects of flavonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells. 1194 20

Lipid content and fatty acid composition were determined in three species of edible fish caught in Senegalese waters during the upwelling season (January, 1993). Sardinella maderensis and Sardinella aurita are fat fish containing more than 5% (fresh wt.) of lipids, whereas Cephalopholis taeniops is a lean fish with approximately 1% of lipids. Skin, liver and muscle were studied for each fish species. About 40 fatty acids were identified by GC and GC/MS as methyl esters and N-acyl pyrrolidides. Palmitic acid was the main acid in the muscle and skin of all samples studied (20-33% of total fatty acids). Oleic acid was the main fatty acid in the liver of S. maderensis (27.2%+/-0.1) and S. aurita (44.7%+/-0.1). Arachidonic acid was a minor component in all samples. The flesh (muscle) of the three fish species contained high concentrations of omega3 polyunsaturated fatty acids (PUFA), ranging from 16.0 to 29.1% and including 20:5 omega3 (eicosapentaenoic acid, EPA) and 22:6 omega3 (docosahexaenoic acid, DHA) acids as major components. These two acids together accounted for 24.7%+/-0.1 and 12.9%+/-0.1 of total acids in the skin of S. maderensis and S. aurita, respectively. The percentages of PUFA found in the fish studied were very similar to those in fish used commercially as sources of PUFA. Muscle sterols, which accounted for 9-11% of total lipids, consisted mainly of cholesterol (up to 97% of total sterols).
Comp Biochem Physiol B Biochem Mol Biol 2002 Mar
PMID:Lipids and fatty acids in muscle, liver and skin of three edible fish from the Senegalese coast: Sardinella maderensis, Sardinella aurita and Cephalopholis taeniops. 1195 21

The effects of dietary lipids and seasonal variation on the lipids of wild and cultured catfish (Japanese catfish, Silurus asotus; Thai catfish, Clarias macrocephalus and hybrid Clarias macrocephalus x Clarias galipinus) were determined by analysis of the lipid content and fatty acid composition of their dorsal meat. The predominant fatty acids of dorsal meat were 16:0, 18:1n-9, 18:2n-6, 20:4n-6 (arachidonic acid, AA), and 22:6n-3 (docosahexaenoic acid, DHA). The DHA content in the diet of Japanese catfish was higher than that in the diet of Thai catfish, and this was reflected in the dorsal meat of the Japanese catfish, which had a remarkably high percentage of DHA compared with the meat of the Thai catfish. Cultured Japanese catfish had a higher percentage of 18:2n-6 than Thai fish and a lower percentage of AA in winter than in summer season. There were also seasonal variations in the percentage of n-6 fatty acids in Japanese catfish. In summer, the fatty acid composition of the cultured Japanese catfish was similar to that of the wild catfish. These fatty acid changes in the lipid classes, triacylglycerol, phosphatidylcholine and phosphatidylethanolamine were similar to those observed for total lipids. These results indicate that the percentage of DHA in the dorsal meat of catfish is influenced by dietary fatty acid, and it may be that it can be increased in cultivated fish by administering a diet containing a large amount of DHA.
Comp Biochem Physiol A Mol Integr Physiol 2002 Jul
PMID:Dietary and seasonal effects on the dorsal meat lipid composition of Japanese (Silurus asotus) and Thai catfish (Clarias macrocephalus and hybrid Clarias macrocephalus and Clarias galipinus). 1204 70

Humans and primates are unique in having adrenals that secrete large amounts of DHEA and DHEA-S in the circulation. These steroids act as precursors of active androgens and estrogen's in a long series of peripheral target intracrine tissues. The marked decline of serum DHEA and DHEA-S concentrations with age in men and women has been incriminated in the development of various pathologies. This study provides detailed information on the effect of a single 50mg oral dose of DHEA on circulating estrogen's as well as androgens and their metabolites over 10h in adult ovariectomised (OVX) Cynomolgus monkeys. Serum DHEA, DHEA-S, testosterone (Testo) and androstenedione (4-dione) concentrations increased rapidly with a maximal value at approximately 1h after DHEA administration followed by a 60-80% decrease during the next 2-6h. An important sulfatation of DHEA occurs through first hepatic pass, thus, leading to a marked increase in serum DHEA-S. Serum androst-5-ene-3beta,17beta-diol and androsterone glucuronide (ADT-G) levels remained elevated on a plateau for 6h. Androstan-3alpha,17beta-diol-glucuronide, estradiol and estrone levels remained unchanged. The present data indicate the predominant transformation of the adrenal precursor DHEA into active androgens in peripheral tissues and support the importance of measurement of circulating glucuronide derivatives as index of peripheral or intracrine androgen formation and action.
J Steroid Biochem Mol Biol 2002 Jun
PMID:Pharmacokinetics of oral dehydroepiandrosterone (DHEA) in the ovariectomised cynomolgus monkey. 1213 6

To investigate the link existing between androgens and human breast cancer, the hormonal milieu present in pre- and post-menopausal women has been translated in an in vitro model utilizing a hormone dependent breast cancer cell line MCF-7 exposed to DHEA, DHEAS, androstenediol, T, DHT with or w/o E(2). DHEAS and androstenediol stimulate the growth of MCF-7 cell line but reduce cell proliferation induced by E(2) (1 nM). T and DHT (1-100 nM) instead inhibit MCF-7 cell proliferation independently on E(2) presence. When we focused our study on the most powerful androgen, DHT alone (100 nM) consistently inhibits MCF-7 cell proliferation by 50% of the basal growth rate and counteracts E(2) proliferative action by 68%. These data correlate well with cell cycle analysis showing an enhanced number of cells in G(0)/G(1) phase after 6 days of DHT treatment. Upon prolonged DHT exposure, Western blotting analysis shows a markedly increased AR content, while immunohistochemistry indicates that it was mostly translocated into the nucleus. So we assumed that the enhanced activation of the AR might inhibit MCF-7 cells proliferation. This assumption is corroborated by the fact that the inhibitory effects induced by DHT on MCF-7 cell proliferation are abrogated in the presence of hydroxyflutamide. Therefore to better investigate the role of AR in inhibiting E(2) action at genomic level, MCF-7 cells were transiently cotransfected with the reporter plasmid XETL carrying firefly luciferase sequence under the control of an estrogen responsive element and the full length AR or with an AR carrying a mutation (Cis 574-->Arg 574) which abolishes its binding to DNA. The over-expression of the AR markedly decreases E(2) signalling which furthermore appears inhibited by simultaneous exposure to DHT but reversed by addition of hydroxyflutamide. The inhibitory effect was no longer noticeable when MCF-7 cells were cotransfected with XETL and the mutant AR. Taken together these data demonstrate that gonadal androgens antagonize MCF-7 proliferation induced by E(2). This seems to be related to the inhibitory effects of the over-expressed AR on E(2) genomic action.
Mol Cell Endocrinol 2002 Jul 31
PMID:Breast cancer: from estrogen to androgen receptor. 1216 Oct 11


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