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PubMed1990

The luteinizing hormone-releasing hormone pulse generator in men: abnormalities and clinical management.

Most men with hypogonadotropic eunuchoidism have absent luteinizing hormone and presumably absent luteinizing hormone-releasing hormone pulses. Pulsatile luteinizing hormone-releasing hormone therapy is effective in restoring normal gonadotropin secretion and testicular function and inducing fertility in men with hypogonadotropic eunuchoidism. Furthermore, pulsatile (versus continuous) luteinizing hormone-releasing stimulation of the pituitary gland is an absolute requirement for normal gonadotropin secretion. Men with idiopathic oligoazoospermia and selective elevation of follicle-stimulating hormone levels have slow luteinizing hormone and presumably luteinizing hormone-releasing pulse frequency. In these men, pulsatile luteinizing hormone--releasing treatment is effective in decreasing serum follicle-stimulating hormone levels, but it is unclear whether spermatogenesis and fertility are improved.

Eunuchism↗
PubMed1992

Increased bioactive luteinizing hormone levels in postmenopausal women with endometrial cancer.

OBJECTIVE: The purpose of our study was to investigate the secretion of immunoactive and bioactive luteinizing hormone in postmenopausal women with endometrial cancer. STUDY DESIGN: Seventeen postmenopausal women with endometrial cancer and nine without cancer were studied. Blood samples were collected at 15-minute intervals for 360 minutes. All samples were assayed for bioactive luteinizing hormone by rat interstitial cell testosterone assay and for immunoactive luteinizing hormone by radioimmunoassay. Serum pooled from 6-hour sampling was assayed for follicle-stimulating hormone, total estradiol, unbound estradiol, and estrone. RESULTS: Patients with endometrial cancer had significantly (p < 0.01) higher bioactive luteinizing hormone levels (mean +/- SE 276 +/- 26 IU/L) as compared with those of control women (144 +/- 18 IU/L). Bioactive/immunoactive ratios of luteinizing hormone were significantly higher (p < 0.01) in women with cancer (5.8 +/- 0.7) than in those without cancer (2.5 +/- 0.5). There was a significant (p < 0.001) positive correlation (r = 0.582) between unbound estradiol levels and bioactive luteinizing hormone concentrations. CONCLUSIONS: There is an increase in bioactive luteinizing hormone secretion in postmenopausal women with endometrial cancer. This could lead to an increase in ovarian androgen production resulting in increased prehormone availability for estrogen formation from peripheral conversion.

Aged↗
PubMed1979

Molecular control of rabbit follicular testosterone production. Role of protein and RNA after stimulation with luteinizing hormone.

The time and dose dependence of the relationship between uptake of labelled precursors into protein and RNA and production of testosterone by rabbit follicles was examined. Although testosterone production was stimulated by luteinizing hormone at concentrations between 0.1 and 10 microgram/ml, the uptake of [3H]leucine into protein was significant only when the concentration of luteinizing hormone was greater than 2.5 microgram/ml. Increased production of testosterone was observed within 15 min of stimulation with luteinizing hormone whereas uptake of [3H]leucine was only significant at 90 min. Puromycin (40 microgram/ml) and cycloheximide (10 microgram/ml) in the presence of luteinizing hormone inhibited the synthesis of both testosterone and protein. However, lower concentrations of puromycin (0.1, 1 and 10 microgram/ml) and cycloheximide (1 microgram/ml) had no effect on luteinizing hormone-induced testosterone production but significantly inhibited protein synthesis by 58, 37, 31 and 71%, respectively. Actinomycin D (20, 80 and 160 microgram/ml) alone and in combination with 5 microgram luteinizing hormone/ml severely inhibited uptake of [3H]uridine into RNA without affecting testosterone production. However, with 1 microgram actinomycin/ml, testosterone production was significantly (P less than 0.01) greater than in the presence of luteinizing hormone alone. These results cast doubt on the obligatory role of RNA and protein synthesis in rabbit ovarian follicular steroidogenesis.

Animals↗
PubMed1992

Isolation and structural elucidation of the geometrical isomers of lutein and zeaxanthin in extracts from human plasma.

All-E-(3R,3'R,6'R)-lutein, all-E-(3R,3'R)-zeaxanthin, all-E-(3R,3'S,6'R)-3'-epilutein and some geometrical isomers of the former two dihydroxycarotenoids have been separated from an extract of human plasma by semipreparative high-performance liquid chromatography on a silica-based nitrile-bonded column. In the order of chromatographic elution, the isolated fractions were identified as all-E-lutein, all-E-zeaxanthin, all-E-3'-epilutein, 9Z-lutein, 9'Z-lutein, a mixture of 13Z-lutein and 13'Z-lutein, 9Z-zeaxanthin, 13Z-zeaxanthin and 15Z-zeaxanthin. The structures of all compounds, including the relative configuration at C(3') and C(6') of the luteins and the position of the stereomutated double bonds in the geometrical isomers, were unambiguously established by 1H nuclear magnetic resonance spectroscopy. The absolute configuration of the three all-E compounds was derived by circular dichroism and is also assumed to be valid for the geometrical isomers. The ultraviolet-visible absorption and mass spectra of each of the individually isolated compounds were also in agreement with the proposed structures.

Carotenoids↗
PubMed2004

Separation of geometric isomers of native lutein diesters in marigold (Tagetes erecta L.) by high-performance liquid chromatography-mass spectrometry.

Lutein is found in many foods; the richest and purest plant source is marigold flower (Tagetes erecta L.). In this plant, lutein is in the form of saturated fatty acid diesters. By using a binary mobile phase consisting of ethyl acetate and acetonitrile-methanol (9:1), improved separation was achieved on a C18-bonded phase. The unique absorption of lutein cis isomers at 330nm was used in combination with MS to identify the novel cis-lutein isomeric dimyristate, myristate-palmitate, dipalmitate, and palmitate-stearate diesters, as well as the rare combinations of both trans- and cis-lutein laurate-palmitate and trans- and cis-lutein myristate-stearate. The presence of the all-trans-lutein laurate-myristate, dimyristate, myristate-palmitate, palmitate-stearate, and distearate diesters, reported by others, was also confirmed.

Chromatography, High Pressure Liquid↗
PubMed2004

Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study.

There is a growing body of evidence which suggests that macular pigment (MP), which is entirely of dietary origin, protects against age-related maculopathy. We evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free lutein) supplement in patients with early age-related maculopathy (ARM), in terms of macular pigment optical density (MPOD) and plasma concentrations of lutein. MPOD was measured using a flicker photometric technique in seven ARM sufferers and six age-matched controls over a period of supplementation which lasted 18-20 weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182 (127)ng ml(-1) to a peak of 1077 (165)ng ml(-1) in ARM patients, and from 152 (57) to 1110 (605)ng ml(-1) in control subjects. Mean MPOD had increased significantly from baseline of 0.24 to a peak of 0.31 in ARM sufferers. This mean increment of 0.07 was the same for the age-matched controls (baseline: 0.20; peak: 0.27). The augmentation of MP, and plasma concentrations of lutein, following supplementation in subjects with ARM provides the first evidence the disease is not associated with intestinal malabsorption of the relevant macular carotenoids, and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects of lutein supplementation, if any, may be extended to subjects with established ARM.

Aged↗
PubMed2005

Lutein absorption is facilitated with cosupplementation of ascorbic acid in young adults.

The objectives of this study were to evaluate the bioavailability of crystalline lutein supplements and compare lutein uptake and clearance in humans simultaneously supplemented with either vitamin C or E. The design was an intervention in which area under the curve (AUC) of lutein was compared with and without each of the supplements. Blood samples were drawn at 0, 2, 4, 6, 8, 12, 16, 24, 32, 60, 128, and 504 hours after the dose to measure serum lutein concentration. Four men and five women, aged 26.6+/-2.6 years, participated in this study. Treatments consisted of 18 mg lutein softgel supplements given either alone (L) or with 2 g vitamin C (LC) or 800 IU vitamin E (LE). Comparison of AUCs for the three treatments was examined using analysis of variance. Individual variations, both between and within subjects, 190- and 70-fold, respectively, were very high. AUC analyses for the first 128 hours postdosing; 2.93+/-1.93, 5.37+/-5.0, and 4.11+/-3.04 micromol . hr/L for L, LC, and LE treatments, respectively; were not significantly different. However, by fitting a multiple regression model of serum concentration over time, lutein is absorbed faster with simultaneous supplementation of vitamin C ( P </=.026). In conclusion, bioavailability of crystalline lutein from supplements varies greatly both within and between subjects and therefore reformulation should be considered. Cosupplementation with another antioxidant may facilitate absorption.

Administration, Oral↗
PubMed2004

Recovery in aqueous two-phase systems of lutein produced by the green microalga Chlorella protothecoides.

In this study the potential use of aqueous two-phase system (ATPS) to establish a viable process for the recovery of lutein from the green microalga Chlorella protothecoides is evaluated. The partitioning behaviour of lutein, a representative model of natural compounds of commercial interest, was investigated in a polyethylene glycol (PEG)-phosphate system. An evaluation of system parameters including PEG molecular mass, the concentrations of PEG, phosphate and product concentration was conducted, to estimate conditions under which lutein partitions preferentially to the top phase whilst cell debris partition to the opposite phase. The necessary addition of ethanol to the ATPS for the dissolution of lutein affected the phase formation and such effect was evaluated using the change in the volume ratio produced. ATPS extraction comprising Vr = 1.0, PEG 8000 22.9% (w/w) and phosphate 10.3% (w/w), pH 7.0 provided the conditions for the concentration of lutein into the upper phase and the cell debris preferentially to the bottom phase. The use of ATPS resulted in a primary recovery process to obtain lutein with an overall product yield of 81.0 +/- 2.8%. The findings reported here demonstrate the potential of ATPS for the further development of a prototype process to recover lutein from C. protothecoides as a first step for the generic application of this technique.

Chlorella↗
PubMed1996

Premature luteinization in in vitro fertilization cycles using gonadotropin-releasing hormone agonist (GnRH-a) and recombinant follicle-stimulating hormone (FSH) and GnRH-a and urinary FSH.

OBJECTIVE: To determine if premature luteinization can occur in GnRH agonist (GnRH-a) and FSH (recombinant FSH and human urinary FSH) IVF cycles and whether premature luteinization affects IVF and clinical outcome. DESIGN: Retrospective evaluation of 171 IVF-ET cycles. The cycles were divided into two groups according to the P level on the day of hCG: group I (serum P </= 0.9 ng/mL [conversion factor to SI unit, 3.180]) and group II (serum P >/= 1.1 ng/mL). MAIN OUTCOME MEASURES: Comparison of cycles characteristics and of cumulative exposure of follicular serum E2, FSH, LH, and P as well as of IVF and clinical outcome were made between the study groups. RESULTS: Twenty-three of the 171 cycles (13.4%) demonstrated premature luteinization. The age of the patients, the E2, and LH exposure were similar between the groups. The number of the ampules of gonadotropins (recombinant FSH and urinary FSH) used and the area under FSH and P curve were higher in cycles with premature luteinization. The area under the FSH curve correlated with the area under the P curve. Similar IVF and clinical outcomes were observed in cycles with and without premature luteinization. CONCLUSION: The greater FSH exposure and its correlation with the P exposure suggest that one of the possible factors inducing premature luteinization is the increased FSH-induced LH receptivity in granulosa cells. No adverse effects of premature luteinization on the IVF and clinical outcome were observed.

Adult↗
PubMed1989

Factors predicting the outcome of varicocele repair for subfertility: the value of the luteinizing hormone-releasing hormone test.

The mechanism by which varicocele caused infertility is not yet clear. Endocrine factors have been suggested to explain impaired spermatogenesis in patients with varicocele. We conducted a prospective study on testosterone and gonadotropin levels and their response to the luteinizing hormone-releasing hormone test to determine the possible role of a hormonal defect in subfertility. Luteinizing hormone-releasing hormone tests were performed on 11 subfertile men with varicocele preoperatively and 3 months postoperatively. The differences in the luteinizing hormone response were statistically significant. The maximal luteinizing hormone levels also were significantly lower in patients whose spermiogram changed postoperatively. No significant changes were noted in testosterone and other gonadotropin levels postoperatively. A prognostic correlation between the change in response of luteinizing hormone to luteinizing hormone-releasing hormone (preoperatively and postoperatively) and improvement in fertility (pregnancy success) was found. We suggest that the luteinizing hormone-releasing hormone test should be considered to estimate the hormonal derangement and also the prognosis of an operation in subfertile men with varicocele.

Adult↗
PubMed2003

Are lutein and zeaxanthin conditionally essential nutrients for eye health?

The carotenoids lutein and zeaxanthin are found in the macula in high concentrations and may play a role in the pathogenesis of age-related macular degeneration (ARMD). Lutein and zeaxanthin may protect the macula and photoreceptor outer segments throughout the retina from oxidative stress and play a role in an antioxidant cascade that safely disarms the energy of reactive oxygen species. Although lutein and zeaxanthin are not essential nutrients, studies are beginning to suggest that they fit the criteria for conditionally essential nutrients. Low plasma lutein and zeaxanthin concentrations or dietary intake are associated with low macular pigment density and increased risk of ARMD. Dietary deprivation of lutein and zeaxanthin in primates causes pathological changes in the macula. Should controlled clinical trials show lutein and/or zeaxanthin supplementation protects against the development or progression of ARMD and other eye diseases, then lutein and zeaxanthin could be considered as conditionally essential nutrients for humans.

Aging↗
PubMed2002

Xanthophyll pigments lutein and zeaxanthin in lipid multibilayers formed with dimyristoylphosphatidylcholine.

This paper reports the research on the effect of two main carotenoid pigments present in the membranes of macula lutea of the vision apparatus of primates, including humans, lutein and zeaxanthin, on the structure of model membranes formed with dimyristoylphosphatidylcholine (DMPC). The effects observed in DMPC are compared to the effects observed in the membranes formed with other phosphatidylcholines (PC): egg yolk PC (EYPC), and dipalmitoyl-PC (DPPC). The analysis has been focused, in particular, on the following aspects of the organization of lipid-carotenoid membranes: aggregation state of pigments, an effect on a thickness of the bilayer and pigment orientation within the membranes. These problems have been addressed with the application of UV-Vis absorption spectroscopy, linear dichroism measurements and the diffractometric technique. (1) Both lutein and zeaxanthin appear in a partially aggregated form in the oriented DMPC multibilayers, even at molar fractions as low as 2 mol.% with respect to lipid. (2) Orientation of the transition dipole of both xanthophylls with respect to the axis normal to the plane of DMPC membrane is different in the case of a monomeric form (34+/-3 degrees in the case of lutein and 26+/-3 degrees in the case of zeaxanthin) but essentially the same in the case of aggregated forms of both pigments (42+/-3 degrees in the case of lutein and 40+/-5 degrees in the case of zeaxanthin). It was found that only lutein has an effect on the increase in the thickness of the DMPC membranes (by about 3 A at 25 degrees C). A similar effect was observed also in the case of DPPC at the same temperatures despite the differences in the physical state of both membrane systems. The differences between the effects of lutein and zeaxanthin observed are interpreted in terms of differences of stereochemical structure of both xanthophylls leading to the different localization in the lipid phase. The results demonstrate significant differences in the behavior of lutein and zeaxanthin in model membranes, which may contribute to their different physiological functions and different efficacy as membrane antioxidants.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Isolation and purification of lutein from the microalga Chlorella vulgaris by extraction after saponification.

A simple and efficient method for the isolation and purification of lutein from the microalga Chlorella vulgaris was developed. Crude lutein was obtained by extraction with dichloromethane from the microalga after saponification. Partition values of lutein in the two-phase system of ethanol-water-dichloromethane at different ratios were measured by HPLC so as to assist the determination of an appropriate condition for washing water-soluble impurities in the crude lutein. Partition values of lutein in another two-phase system of ethanol-water-hexane at different ratios were also measured by HPLC for determining the condition for removing fat-soluble impurities. The water-soluble impurities in the crude lutein were removed by washing with 30% aqueous ethanol, and the fat-soluble impurities were removed by extraction with hexane. The final purity of lutein obtained was 90-98%, and the yield was 85-91%.

Chlorella↗
PubMed1999

Isolation and structural elucidation of (13Z,13'Z,3R,3'R,6'R)-lutein from marigold flowers, kale, and human plasma.

(13Z,13'Z,3R,3'R,6'R)-Lutein has been isolated and purified from extracts of marigold flowers, fresh raw kale (Brassica oleracea var. Acephala), and human plasma and fully characterized by (1)H and (13)C NMR, UV/vis, and MS. While the concentration of (13Z, 13'Z)-lutein in kale and human plasma compared to (all-E,3R,3'R, 6'R)-lutein was found to be quite low, this compound was readily isolated by fractional crystallization of lutein from marigold extracts. Thus, the mother liquors from two consecutive crystallizations of lutein from a saponified extract of marigold flowers were enriched in (13Z,13'Z)-lutein (8.7% of total carotenoids) and employed for the isolation of this compound by HPLC. The identity of the di-Z-lutein in kale and human plasma has been established by comparison of the HPLC-UV/vis-MS profiles of the purified compounds with those of a fully characterized sample, isolated from marigolds. 3-Hydroxy-beta,epsilon-caroten-3'-one and 3'-epilutein have also been identified in extracts from marigolds.

Brassica↗
PubMed2003

Comparison of lutein bioavailability from vegetables and supplement.

Lutein is a carotenoid present in dark green leafy vegetables and it may be involved in the prevention of several diseases related to oxidative stress. The aim of this study was to evaluate bioavailability of lutein from different food sources (150 g spinach and 200 g broccoli) and a supplement in oil (300 mg VEGEX), all providing about 9 mg lutein. Eight healthy females were instructed to eat a low-carotenoid diet for the period of experimentation. On three different occasions, three weeks apart, volunteers ate the lutein sources together with 10 g olive oil and 40 g bread. Blood samples were collected just before eating, every two hours for 12 hours, and at 24, 32, 56, 80 and 104 hours. Lutein concentration increased significantly after six to eight hours and peaked after 10-12 hours, with the highest concentration reached after VEGEX intake. Lutein concentration remained significantly elevated for up to 80 hours (VEGEX and spinach). On the whole, our results suggest that the intake of one single dose of lutein from different sources is able to bring about a significant plasma response in the short term.

Adult↗
PubMed2004

Dietary lutein reduces ultraviolet radiation-induced inflammation and immunosuppression.

Ultraviolet radiation (UVR) promotes skin cancer development by mutagenic, immunosuppressive, and oxidative-stress-inducing mechanisms; however, certain antioxidants may counteract and prevent UVR-induced photodamage. Lutein is a xanthophyll carotenoid with potent antioxidant activity. Because reactive oxygen species (ROS) are believed to have a role in UVR-induced skin damage, we investigated whether lutein can modify UVR effects including the tissue swelling response to midrange UVR (280-320 nm, ultraviolet B (UVB) radiation) and UVB suppression of contact hypersensitivity (CHS) in both the local and the systemic models of UV-induced immunosuppression. We found that compared to mice fed the standard laboratory diet, mice fed dietary lutein demonstrated significant inhibition of ear swelling owing to UVB radiation. Mice exposed to 1700 J per m2 UVB radiation four times at daily intervals and then sensitized to dinitrofluorobenzene at the site of irradiation showed a decreased CHS response upon challenge. This suppression by UVB radiation was significantly inhibited by lutein feeding. When UVB radiation was given at a single dose of 10,000 J per m2 to inhibit the induction of CHS at a distant, nonirradiated site, no effect of lutein was seen. Finally, lutein accumulated in the skin of mice following diet supplementation and was shown to decrease ROS generation following UVR exposure. Thus, lutein modulates the skin's response to UVR and may contribute to the defense against some of the deleterious effects of solar radiation.

Animal Feed↗
PubMed1999

Bioavailability of lutein from vegetables is 5 times higher than that of beta-carotene.

BACKGROUND: To gain more insight into the relation between vegetable consumption and the risk of chronic diseases, it is important to determine the bioavailability of carotenoids from vegetables and the effect of vegetable consumption on selected biomarkers of chronic diseases. OBJECTIVE: To assess the bioavailability of beta-carotene and lutein from vegetables and the effect of increased vegetable consumption on the ex vivo oxidizability of LDL. DESIGN: Over 4 wk, 22 healthy adult subjects consumed a high-vegetable diet (490 g/d), 22 consumed a low-vegetable diet (130 g/d), and 10 consumed a low-vegetable diet supplemented with pure beta-carotene (6 mg/d) and lutein (9 mg/d). RESULTS: Plasma concentrations of vitamin C and carotenoids (ie, alpha-carotene, beta-carotene, lutein, zeaxanthin, and beta-cryptoxanthin) were significantly higher after the high-vegetable diet than after the low-vegetable diet. In addition to an increase in plasma beta-carotene and lutein, the pure carotenoid-supplemented diet induced a significant decrease in plasma lycopene concentration of -0.11 micromol/L (95% CI: -0.21, -0.0061). The responses of plasma beta-carotene and lutein to the high-vegetable diet were 14% and 67%, respectively, of those to the pure carotenoid- supplemented diet. Conversion of beta-carotene to retinol may have attenuated its plasma response compared with that of lutein. There was no significant effect on the resistance of LDL to oxidation ex vivo. CONCLUSIONS: Increased vegetable consumption enhances plasma vitamin C and carotenoid concentrations, but not resistance of LDL to oxidation. The relative bioavailability of lutein from vegetables is higher than that of beta-carotene.

Adolescent↗
PubMed1995

Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses.

Single equimolar doses (0.5 mumol/kg body wt) of lutein and/or beta-carotene in true solution in oil were given to eight adult subjects and 13 blood samples were taken during the subsequent 840 h. Whereas the mean serum concentration of lutein showed a single maximum at 16 h, that of beta-carotene peaked at 6 h and then again at 32 h. Subsequently, lutein and beta-carotene were cleared at approximately the same rate from the serum. The mean (+/- SEM) areas under the curve (AUCs) for lutein and beta-carotene during the first 440 h differed significantly: 59.6 +/- 9.0 and 26.3 +/- 6.4 mumol.h/L, respectively (P < 0.005). AUC values did not correlate with initial serum concentrations of the given carotenoid or with the order of dosing. When combined in the same dose, beta-carotene significantly reduced the serum AUC values for lutein to 54-61% of control values (P < 0.025), whereas lutein reduced the AUC value for beta-carotene in five subjects but enhanced it in three subjects. Effects of lutein on the AUC for beta-carotene were inversely related to the AUC for beta-carotene alone. Thus, carotenoids clearly interact with each other during intestinal absorption, metabolism, and serum clearance, although individual responses can differ markedly.

Administration, Oral↗