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PubMed1999

Human granulosa cells express integrin alpha2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization.

Previously, it has been shown that integrin alpha6beta1 expressed on human granulosa cells regulates luteinization in co-operation with its ligand, laminin. In this study, integrin alpha2 was immunohistochemically demonstrated to be expressed on granulosa and large luteal cells. It was also detected on luteinizing theca interna cells after ovulation. Immunoreactive collagen type IV, which is one of the ligands for integrin alpha2beta1, was detected around granulosa cells in the pre-ovulatory follicles and its expression was rapidly increased during ovulation. By flow cytometry, collagen type IV was detected on the cell surface of luteinizing granulosa cells isolated from pre-ovulatory follicles, confirming the physiological interaction between granulosa cells and collagen type IV. Collagen type IV in follicular fluid was positively related with progesterone concentration. In 4-day cultures of granulosa cells, collagen type IV in the media was significantly increased by human chorionic gonadotrophin (HCG). The progesterone production was significantly attenuated when granulosa cells were cultured on collagen type IV-coated dishes, suggesting that collagen type IV suppresses granulosa cell luteinization. These findings show that collagen type IV, a ligand for integrin alpha2beta1, is rapidly produced around luteinizing granulosa cells during ovulation, probably under the control of luteinizing hormone (LH) and suggest that collagen type IV is a new parameter and/or regulator of granulosa cell luteinization in the periovulatory phases.

Antigens, CD↗
PubMed2002

[Study of effects of leptin on cultured human luteinized granulosa cell function].

OBJECTIVE: To assess the effects of leptin on follicle-stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) induced production of estradiol (E(2))-17beta and progesterone (P) in cultured human luteinized granulosa cell (GC). METHODS: Human luteinized GCs were obtained from pre-ovulatory follicles in an in-vitro fertilization program, and were cultured for 24 hours in the presence of leptin (3.0 ng/ml) or FSH (1.0 ng/ml) or IGF-I (30.0 ng/ml) alone, leptin with FSH or IGF-I or both, and FSH with IGF-I. The conditioned media were aspirated for measuring E(2) and P content. Luteinized GC were also counted for cell number and detected the expression of the leptin receptor by reverse transcription polymerase chain reaction analysis. RESULTS: In cultured luteinized GC system, leptin or FSH or IGF-I alone did not affect the growth of cultured human luteinized GC. Leptin alone or in the presence of FSH had no effect on E(2) production. E(2) levels in culture media without leptin or FSH were (0.103 +/- 0.036) pmol/1 000 cells, (0.323 +/- 0.042) pmol/1 000 cells respectively. When cultured with leptin alone or with leptin and FSH, E(2) levels were (0.120 +/- 0.008) pmol/1 000 cells, (0.343 +/- 0.034) pmol/1 000 cells. Leptin significantly inhibited FSH + IGF-I or IGF-I induced E(2) production. E(2) levels decreased from (0.318 +/- 0.037) pmol/1 000 cells to (0.193 +/- 0.025) pmol/1 000 cells (IGF-I) (P < 0.05) and from (0.493 +/- 0.036) pmol/1 000 cells to (0.251 +/- 0.033) pmol/1 000 cells (FSH + IGF-I) (P < 0.01). However, the production of P did not change. The leptin receptor expression was demonstrated in luteinized GC. CONCLUSIONS: Leptin may directly attenuate the IGF-I or IGF-I and FSH-stimulated E(2) synthesis in cultured human luteinized GC by the leptin receptor mechanism.

Carrier Proteins↗
PubMed1988

The natural history of theca lutein cysts.

The histories of 386 patients with untreated hydatidiform mole were reviewed to define the clinical aspects of accompanying theca lutein cysts. These cysts occurred in 102 patients (26.4%), with three patients experiencing cyst-related complications. Mean cyst size at diagnosis was 7.3 cm (3-20 cm), and did not correlate with post-molar trophoblastic disease development. Bilateralism occurred more often in patients developing post-molar trophoblastic disease. In patients with post-molar trophoblastic disease, 83% (45 of 54) experienced theca lutein cyst regression and 16.7% an increase in cyst size with falling beta-hCG titers. Post-molar trophoblastic disease developed in 44 patients. Theca lutein cyst growth occurred in 31.8% of the patients with beta-hCG plateau/rise and in 4.5% with falling titers. Disappearance of theca lutein cysts before diagnosis of post-molar trophoblastic disease occurred in 31.8%. Theca lutein cysts persisted in three patients for long periods (15-18 weeks) after beta-hCG regression. We conclude that theca lutein cysts commonly accompany hydatidiform mole and are associated with an increased risk of post-molar trophoblastic disease, a risk that is higher with cyst bilateralism or severe complications of hydatidiform mole. Theca lutein cysts uncommonly have serious complications; their clinical behavior does not depend entirely on changes in beta-hCG levels, as cysts may persist for long periods after beta-hCG regression.

Adolescent↗
PubMed1995

Lutein, lycopene, and their oxidative metabolites in chemoprevention of cancer.

Numerous epidemiological studies have demonstrated that consuming large quantities of fruits and vegetables reduces the risk for several types of human cancers. Carotenoids are abundant in fruits and vegetables and have been extensively studied as cancer preventive agents. A proposed mechanism of action for the protective effect of carotenoids against cancer is based on their antioxidant capability. Recently, we have isolated and characterized 14 new carotenoids, including seven metabolites from the extracts of human serum/plasma. This brings the total number of identified blood carotenoids to 21. Lutein and lycopene, abundant in most fruits and vegetables as well as human serum, have been shown to possess strong antioxidant capability. Among the metabolites of lutein, four results from oxidation and two from non-enzymatic dehydration. The metabolite of lycopene has been identified as 5,6-dihydroxy-5,6-dihydrolycopene, which apparently results from oxidation of lycopene to an intermediate, lycopene epoxide. This intermediate may undergo metabolic reduction to form the lycopene metabolite. Although in vivo oxidation of lutein to its metabolites has been demonstrated based on data obtained from two human studies, in vivo oxidation of lycopene to its metabolite has not yet been established. Recent preliminary studies involving healthy subjects ingesting purified lutein and zeaxanthin (a dietary dihydroxycarotenoid isomeric to lutein) are presented. We propose a possible antioxidant mechanism of action for lutein and lycopene that leads to formation of the oxidation products of these promising chemopreventive agents.

Anticarcinogenic Agents↗
PubMed1977

Potency of synthetic luteinizing hormone releasing hormone preparations in rat anterior pituitary cell cultures.

Selected synthetic luteinizing hormone releasing hormone preparations were assayed, and their potencies were determined relative to one sample utilizing primary cultures of enzymatically dispersed rat anterior pituitary cells. Preliminary cell culture experiments indicated that luteinizing hormone releasing hormone had to be in constant contact with cells for continued luteinizing hormone secretion. Luteinizing hormone levels in media reached a maximum concentration after 4 hr of continuous luteinizing hormone releasing hormone exposure. Cell culture bioassay was selected over the bioassay employing chronically ovariectomized steroid-blocked rats due to greater sensitivity and economy. The assay of each luteinizing hormone releasing hormone preparation was replicated four to seven times. Preparations from several companies were less potent (p less than 0.05) than the reference product. Contaminants were disclosed by TLC in preparations with potencies lower than the reference product.

Animals↗
PubMed2006

Kinetic modeling of lutein production by heterotrophic Chlorella at various pH and temperatures.

Kinetics of lutein production by heterotrophic Chlorella protothecoides was investigated with respect to pH and temperature. Flask cultures with initial pH 5.0-8.0 were carried out, and it was found that pH 6.0 was optimal for the algal growth. Further tests in fermentors showed that the highest biomass concentration, maximum cellular lutein content and lutein yield were achieved at pH 6. 6. In addition, it was shown that optimal biomass concentration and lutein yield were obtained at 28 degrees C, while application of 35 degrees C resulted in the highest cellular lutein content. A mathematical model was developed for the description of the processes under these cultivation conditions and the kinetic model fitted well to the experimental data. The obtained results may contribute to the commercial production of lutein by C. protothecoides.

Chlorella↗
PubMed1997

A one year study of the macular pigment: the effect of 140 days of a lutein supplement.

A low density of macular pigment may represent a risk factor for age-related macular degeneration (AMD) by permitting greater blue light damage. This study was carried out to determine the effects on macular pigment optical density of dietary supplementation with lutein, one of the pigment constituents. Two subjects consumed lutein esters, equivalent to 30 mg of free lutein per day, for a period of 140 days. Macular pigment optical density was determined by heterochromatic flicker photometry before, during, and after the supplementation period. Serum lutein concentration was also obtained through the analysis of blood samples by high-performance liquid chromatography. Twenty to 40 days after the subjects commenced taking the lutein supplement, their macular pigment optical density began to increase uniformly at an average rate of 1.13+/-0.12 milliabsorbance units/day. During this same period, the serum concentration of lutein increased roughly tenfold, approaching a steady state plateau. The optical density curve eventually levelled off 40 to 50 days after the subjects discontinued the supplement. During the same 40 to 50 days, the serum concentration returned to baseline. Thereafter, little or no decrease in optical density was observed. The mean increases in the macular pigment optical density were 39% and 21% in the eyes of the two subjects respectively. In conclusion, the modest period of supplementation has been estimated to have produced in the subjects a 30 to 40% reduction in blue light reaching the photoreceptors, Bruch's membrane, and the retinal pigment epithelium, the vulnerable tissues affected by AMD.

Adult↗
PubMed2002

Serum depletion and bioavailability of lutein in type I diabetic patients.

BACKGROUND: Lutein, a non-provitamin A carotenoid, is frequently consumed in the human diet. It is distributed preferentially in certain human tissues (i. e., retina) and shows a high antioxidant activity. Type 1 diabetic patients have been considered to be at risk of increased oxidative stress that may contribute to accelerated atherogenesis and to the microangiopathic complications of the disease. AIM OF THE STUDY: To assess the influence of type 1 diabetes mellitus on the serum depletion rate and bioavailability of lutein. SUBJECTS AND METHODS: Ten type 1 diabetics and eight controls consumed a low carotenoid diet for 21 days and the bioavailability study was performed in 7 diabetics and 5 controls on day 15 with the administration of a capsule of lutein esters from marigold extract. Samples were collected at baseline and on days 1, 2, 3, 6, 11, 15 (eight times during 9 h), 16, 17 and 21. Lutein and other carotenoids were determined by HPLC in triglyceride-rich lipoprotein (TRL) fractions and plasma or serum. RESULTS: Serum depletion curve, area of concentrations under time curve (AUC) and final concentration percentages were similar in diabetics and controls. In the bioavailability study, all-trans-lutein increased in both groups and AUC, maxima concentrations in TRL and serum and time required for maxima concentration in serum were similar in diabetics and controls. CONCLUSIONS: These data suggest that in the group of patients assessed, type 1 diabetes mellitus does not apparently influence the absorption and depletion rate of lutein in serum.

Adult↗
PubMed1989

Effects of clomiphene citrate on episodic luteinizing hormone secretion throughout the menstrual cycle.

Pituitary luteinizing hormone secretory dynamics (pulse frequency and amplitude) were evaluated in eight normal women administered clomiphene citrate or placebo. After 5 days of treatment clomiphene citrate was found to increase mean luteinizing hormone secretion by increasing the amount of pituitary luteinizing hormone released per pulse. No change in pituitary luteinizing hormone interpulse interval was found in the follicular phase of the cycle, although a faster pulse frequency in the luteal phase was found after clomiphene citrate when compared with placebo. No differences were found in the luteal phase (pulse frequency, amplitude, and mean luteinizing hormone level) after clomiphene citrate versus placebo in the volunteers. These data suggest that the principal mechanism of action of clomiphene citrate is an increase in the concentration of hypothalamic gonadotropin releasing hormone into the hypothalamic-pituitary portal circulation, with a resultant increase in pituitary luteinizing hormone secretion.

Adult↗
PubMed1990

Nature of gonadotropin-releasing hormone self-priming of luteinizing hormone secretion during the normal menstrual cycle.

To investigate further the nature of the gonadotropin-releasing hormone self-priming effect on luteinizing hormone release, we administered two submaximal doses of gonadotropin-releasing hormone 2 hours apart to women at three stages of the menstrual cycle and analyzed the resultant luteinizing hormone secretory episodes with deconvolution analysis. When the characteristics of the secretory episodes associated with the second gonadotropin-releasing hormone challenge were compared with those associated with the first, both an enhanced maximal secretory rate and mass of luteinizing hormone secreted was demonstrable at each phase of the cycle. No differences in the luteinizing hormone secretory event half-duration were detected when the responses to the first and second gonadotropin-releasing hormone doses were compared. These data confirm the gonadal hormone milieu-associated self-priming effect of gonadotropin-releasing hormone on luteinizing hormone release and indicate that it is the rate with which luteinizing hormone molecules are discharged from the pituitary gland, rather than the duration of the secretory episode itself, that provides for the self-priming effect.

Adolescent↗
PubMed1992

Use of urinary luteinizing hormone immunoassays in the assessment of luteal function in infertile women.

It has been suggested that the chronologic date of an endometrial biopsy performed to evaluate luteal adequacy should be based on the date of the luteinizing hormone surge rather than the date of the next menstrual period. Sixty-four infertile women used a urinary luteinizing hormone immunoassay to identify the luteinizing hormone surge; timed serum progesterone level tests and an endometrial biopsy were then performed. An out-of-phase endometrium was identified in 26.6% of cycles dated traditionally and 28.1% of cycles dated from the luteinizing hormone surge. No relationship was identified between progesterone levels and endometrial biopsy results when the next menstrual period was used. When the luteinizing hormone surge was used no progesterone cutoff value could be identified that would reliably distinguish between in-phase and out-of-phase cycles. Use of a urinary luteinizing hormone immunoassay offers no advantage over the next menstrual period and does not lead to better agreement between histologic and chronologic dating.

Corpus Luteum↗
PubMed2006

Lutein effect on retina and hippocampus of diabetic mice.

Oxidative stress markers and functional tests were studied to confirm early biochemical and functional changes in retina and hippocampus of diabetic mice. The effects of lutein treatment were also tested. Mice were induced diabetic by alloxan injection and divided into subgroups: control, control+lutein, diabetic, diabetic+lutein, diabetic+insulin, and diabetic+insulin+lutein. Treatments started on Day 4 after alloxan injection and animals were sacrificed on Day 14. Malondialdehyde and glutathione concentrations and glutathione peroxidase activity were measured as oxidative stress markers. The following functional tests for retina and hippocampus were performed: electroretinogram and Morris water maze test. NFkappaB activity was also measured. Oxidative stress and NFkappaB activity increase in the retina and hippocampus after 15 days of diabetes. Impairment of the electroretinogram and a correlation between latencies of the water maze test and glycated hemoglobin (HbA1c) levels were observed. Lutein prevented all these changes even under hyperglycemic conditions. Retina appears to be affected earlier than hippocampus by diabetes-induced oxidative stress. Although a proper glycemic control is desirable in preventing the development of diabetic complications, it is not sufficient to prevent them completely. Lutein could be an appropriate coadjuvant treatment for the changes observed in this study.

Animals↗
PubMed1996

Regulation of rat granulosa cell alpha-inhibin expression by luteinizing hormone, estradiol, and progesterone.

OBJECTIVE: Our purpose was to assess the effects of follicle-stimulating hormone, luteinizing hormone, forskolin (an adenylyl cyclase activator), estradiol, and progesterone on alpha-inhibin promoter activity in an in vitro fusion gene-transfection system. STUDY DESIGN: A fusion gene consisting of the alpha-inhibin 5' flanking and promoter regions linked to the chloramphenicol acetyl transferase reporter gene was constructed. A granulosa cell line originally derived from an inbred strain of Berlin Duckrey rats was transiently transfected with the fusion gene. Fusion gene activity was determined by measuring chloramphenicol acetyl transferase activity in transfected cells. RESULTS: Both follicle-stimulating hormone and luteinizing hormone activated the alpha-inhibin promoter. Activity in response to combined luteinizing hormone-forskolin treatment was greater than the summation of the activities of the two treatments individually, suggesting that the effects of luteinizing hormone might be partially mediated by second messengers other than cyclic adenosine monophosphate. Gonadotropin-stimulated activity was diminished by estradiol and combined estradiol-progesterone treatments. CONCLUSIONS: The stimulatory effects of follicle-stimulating hormone and luteinizing hormone on alpha-inhibin production are mediated at least in part by stimulation of the alpha-inhibin promoter. The stimulatory effects are blunted by estradiol-progesterone. These observations may partially explain how alpha-inhibin is down-regulated in vivo in response to the preovulatory luteinizing hormone surge.

Animals↗
PubMed1990

Influence of different types of antiandrogens on luteinizing hormone-releasing hormone analogue-induced testosterone surge in patients with metastatic carcinoma of the prostate.

The long-term effect of the luteinizing hormone-releasing hormone analogue-induced initial testosterone surge in the treatment of patients with metastatic carcinoma of the prostate still is unknown. However, acute worsening of the disease has been reported in up to 10% of the patients. To prevent such tumor flare we investigated the endocrinological effects of different types of antiandrogens administered in addition to a luteinizing hormone-releasing hormone analogue. Patients with newly diagnosed metastatic prostate cancer were pre-treated with either the steroidal antiandrogen cyproterone acetate (6) or the nonsteroidal antiandrogen flutamide (5) for 1 week before the initial injection of the depot luteinizing hormone-releasing hormone analogue Zoladex. In another 5 patients flutamide was first given 24 hours before Zoladex therapy was started. Luteinizing hormone, testosterone and prostatic acid phosphatase during month 1 of luteinizing hormone-releasing hormone analogue therapy were compared to data obtained in 5 patients treated by Zoladex alone. Only pre-treatment with cyproterone acetate was capable of preventing the Zoladex-induced testosterone surge. However, both pre-treatment regimens with either cyproterone acetate or flutamide for 1 week prevented an initial increase in prostatic acid phosphatase beyond pre-treatment levels in all patients. In contrast, in 4 of 5 patients treated with Zoladex alone and in 2 of 5 pre-treated with flutamide for 1 day an initial increase in prostatic acid phosphatase beyond the pre-treatment values was seen. Our data indicate that pre-treatment with flutamide for only 1 day may not be sufficient to prevent a luteinizing hormone-releasing hormone analogue-induced tumor flare in all cases.

Acid Phosphatase↗
PubMed1997

Further studies on the suppression of luteinizing hormone release due to activation of medial preoptic-anterior hypothalamic area mu-opioid receptors.

Our laboratory has previously demonstrated that specific activation of mu-opioid receptors in the medial preoptic-anterior hypothalamic area with [D-Ala2, N Me-Phe4, Gly-ol5]-enkephalin (DAGO) suppresses luteinizing hormone secretion in the ovariectomized rat [29]. In the present study, three experiments were undertaken to ascertain whether changes in the activity of norepinephrine or dopamine neurons modulate the decrease in luteinizing hormone release in response to DAGO. The first experiment utilized push-pull perfusion in conjunction with HPLC to assess in vivo norepinephrine release in the medial preoptic-anterior hypothalamic area in response to perfusion of this site with DAGO (5 micrograms/h). DAGO significantly decreased luteinizing hormone release, but perfusate norepinephrine levels did not change. In the second experiment, push-pull perfusion in the medial preoptic-anterior hypothalamic area with cerebrospinal fluid (CSF) or CSF containing DAGO was done in rats pretreated with the norepinephrine synthesis inhibitor, FLA-63. This drug pretreatment had no effect on the DAGO-induced suppression of luteinizing hormone secretion. In experiment 3, push-pull perfusion in the medial preoptic-anterior hypothalamic area with CSF followed by CSF containing DAGO was done in rats pretreated with vehicle, or a dopamine receptor antagonist, either pimozide or d-butaclamol. Neither dopamine receptor antagonist had any effect on the DAGO-induced suppression of luteinizing hormone release. Thus, these studies do not support a role for alterations in the activity of norepinephrine or dopamine neurons in mediating the suppression of luteinizing hormone release in response to activation of mu-opioid receptors in the medial preoptic-anterior hypothalamic area in the ovariectomized rat.

Animals↗
PubMed2000

Organization of mixed monomolecular layers formed with the xanthophyll pigments lutein or zeaxanthin and dipalmitoylphosphatidylcholine at the argon-water interface.

Two-component monomolecular layers were formed with two xanthophyll pigments, lutein and zeaxanthin and dipalmitoylphosphatidylcholine (DPPC), at the argon-water interface. Analysis of the mean molecular area parameters versus molar fraction of the xanthophyll component shows large overadditivity (ca. 50 A2 in the case of zeaxanthin and 150 A2 in the case of lutein) in the region of low molar fractions of carotenoids (maximum at 5 mol% in the case of zeaxanthin and at 20 mol% in the case of lutein). The experimental values of a mean molecular area are in good agreement with the values expected, based on the additivity rule at high molar percentages of the xanthophylls. Absorption spectroscopy of a single monolayer at the argon-water interface in the UV-Vis region has also been applied to analyze the formation of molecular assemblies of lutein in monomolecular films. The differences in the organization of lutein-DPPC and zeaxanthin-DPPC monolayers are interpreted in terms of the aggregation of xanthophyll pigments in the layers and different orientation of both xanthophylls at the interface. The results are discussed in relation to possible physiological functions of lutein and zeaxanthin in the membranes of the retina of an eye.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Genotypic differences in chlorophyll, lutein, and beta-carotene contents in the fruits of actinidia species.

Chlorophyll, lutein, and beta-carotene contents in Actinidia fruits were determined by high-performance liquid chromatography in various genotypes, including five Actinidia deliciosa, seven Actinidia chinensis, two Actinidia rufa, five Actinidia arguta, and three interspecific hybrids. The concentrations of chlorophyll, lutein, and beta-carotene in the fruit of A. deliciosa Hayward were 1.65, 0.418, and 0.088 mg/100 g fresh weight, respectively. Of A. deliciosa cultivars, Koryoku showed significantly higher concentrations in chlorophyll, lutein, and beta-carotene than Hayward. In most cultivars of A. chinensis, although both chlorophyll and lutein contents were significantly lower than in Hayward, the beta-carotene content tended to be slightly higher. In A. rufa, A. arguta, and their interspecific hybrids, the contents of chlorophyll, lutein, and beta-carotene were much higher than in Hayward. In particular, these fruits were found to be the richest dietary source of lutein among commonly consumed fruits.

Actinidia↗
PubMed1997

The possible significance of parallel changes in plasma lutein and retinol in Pakistani infants during the summer season.

Recent evidence suggests that plasma lutein is better correlated than either beta-carotene or lycopene with its respective carotenoid intake and therefore may be a better marker of vegetable intake than either beta-carotene or lycopene. In the study reported in this paper, measurements of plasma carotenes and retinol were made in infants from two villages near Peshawar in the North West Frontier Province, Pakistan, in July and November 1993. The approximate age at the start was 14 months, and 101 boys and ninety girls completed the study. Of the usual plasma carotenes, only lutein was measurable in all samples and was correlated with retinol in both boys (r 0.38, P < 0.0001; r 0.35, P < 0.001) and girls (r 0.21, P = 0.038; r 0.0307, P = 0.003) at the two time points respectively. In addition, the change in lutein was even more strongly correlated with the change in retinol in both boys (r 0.453, P < 0.0001) and girls (r 0.439, P < 0.0001). In August beta-carotene was measurable in approximately 8 % of samples and this increased to 31 % in November but there was no correlation between beta-carotene and retinol at any time. There were negligible amounts of lycopene and beta-cryptoxanthin in plasma at both time points. The mean concentration of plasma retinol in the infants was 0.66 mumol/l at baseline and 59% of the infants had retinol concentrations < 0.7 mumol/l. In addition, there were fifteen infants whose levels were below 0.35 mumol/l suggesting that vitamin A status in the population was marginal. Food intake of the infants was not monitored in the present study but breast feeding continues for up to 2 years in this part of Pakistan and most infants would be weaned onto selected foods eaten by the family. The close correlation between plasma lutein and retinol suggests that the increase in retinol over the summer season may be attributable to an increased availability of green vegetables to the families. The source of lutein to the infants is most likely to be the breast milk since such vegetables are unlikely to be given to infants except to suck as a weaning food. The results may indicate the potential usefulness of plasma lutein as a marker of changes in vegetable intake and changes in vitamin A status in Third World infants and children.

Biomarkers↗