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PubMed2004

Lutein and zeaxanthin and their potential roles in disease prevention.

Lutein and zeaxanthin are xanthophyll carotenoids found particularly in dark-green leafy vegetables and in egg yolks. They are widely distributed in tissues and are the principal carotenoids in the eye lens and macular region of the retina. Epidemiologic studies indicating an inverse relationship between xanthophyll intake or status and both cataract and age-related macular degeneration suggest these compounds can play a protective role in the eye. Some observational studies have also shown these xanthophylls may help reduce the risk of certain types of cancer, particularly those of the breast and lung. Emerging studies suggest as well a potential contribution of lutein and zeaxanthin to the prevention of heart disease and stroke. Even as the evidence for a role of lutein and zeaxanthin in disease prevention continues to evolve, particularly from human studies directed to their bioavailability, metabolism, and dose-response relationships with intermediary biomarkers and clinical outcomes, it is worth noting that recommendations to consume foods rich in xanthophylls are consistent with current dietary guidelines.

Aging↗

PubMed1973

Light and electron microscope localization of binding sites of antibodies against ovine luteinizing hormone and its two subunits in rat adenohypophysis using peroxidase-labeled antibody technique.

The binding sites of antisera generated in the guinea pig against ovine luteinizing hormone (oLH) and its two subunits (oLHalpha and oLHbeta) have been localized in rat anterior pituitaries taken from normal or castrated males and from ovariectomized females with the peroxidase-labeled antibody method, using light and electron microscopy. With the light microscope, the cells positive with antiserum to ovine luteinizing hormone (A-oLH) were violet after the Alcian blue-periodic acid-Schiff (AB-PAS) staining; they were also positive for A-oLHalpha and for A-oLHbeta and, from castrated males, they displayed an increased affinity for A-oLHbeta. Another cell type which was blue after the AB-PAS method reacted with the A-oLHalpha only; these cells, presumably thyrotropic cells, were retracted after castration and, besides their affinity for A-oLHalpha, acquired an affinity for A-oLHbeta. As seen through the electron microscope, two cell types were positive for A-oLH, A-oLHbeta, and A-oLHalpha and may be identified as luteinizing hormone-secreting cells. Type A cells were characterized by two classes of rounded, secretory granules. Type B cells were smaller and contained only small secretory granules. 1 mo after the rats were castrated the type A cells were hypertrophied and vacuolized. In both cases the secretory granules were the main sites of the antigenicity with the three antisera. A positive reaction was also found in the cytoplasm, particularly in hypertrophied cells from ovariectomized females and with A-oLHbeta. The cisternae of the rough endoplasmic reticulum were usually negative, except in highly degranulated cells from ovariectomized females and with A-oLHbeta.

Animals↗

PubMed2004

Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin.

BACKGROUND: Zeaxanthin is hypothesized to reduce the risk of age-related macular degeneration; however, kinetic information is limited. OBJECTIVES: The objective was to investigate the plasma kinetics of synthetic zeaxanthin after repeated oral doses and to assess the possible influence of other carotenoids on plasma zeaxanthin concentrations. DESIGN: After a run-in of 3 d, 20 healthy volunteers assigned to 2 parallel dose groups received once daily oral doses of either 1 mg (1.76 micro mol) or 10 mg (17.6 micro mol) zeaxanthin for 42 d. Plasma concentration-time profiles on days 1 and 42, concentrations immediately before zeaxanthin intake during the dosing period, and concentrations after the last dose until day 76 were monitored. RESULTS: all-E-Zeaxanthin concentrations increased from 0.048 +/- 0.026 micro mol/L at baseline to 0.20 +/- 0.07 and 0.92 +/- 0.28 micro mol/L with 1 and 10 mg zeaxanthin, respectively. The dose-normalized bioavailability of all-E-zeaxanthin after the10-mg dose was 40% lower (P < 0.001) than after the 1-mg dose. Other kinetic parameters did not differ significantly between groups. After 17 d of dosing, >90% of steady state concentrations were reached, which was compatible with an effective half-life for accumulation of 5 d. The terminal elimination half-life was 12 +/- 7 d (n = 20). The time course of plasma all-E-3-'dehydro-lutein concentrations resembled that of all-E-zeaxanthin. The data provided evidence that all-E-3-'dehydro-lutein was derived from all-E-zeaxanthin. Concentrations of other carotenoids were not affected. Zeaxanthin was well tolerated. CONCLUSION: Long-term oral intake of 1 and 10 mg zeaxanthin as beadlets increases plasma zeaxanthin concentrations approximately 4- and 20-fold, respectively. Evidence that all-E-3-dehydro-lutein is formed from zeaxanthin was strong.

Administration, Oral↗

PubMed1995

Luteinized unruptured follicle: morphology, endocrine function and blood flow changes during the menstrual cycle.

A case of spontaneous luteinized unruptured follicle syndrome is presented with full documentation of hormonal, morphological and haemodynamic changes. Changes in uterine blood flow were also noted. Growth of the leading follicle was slow during the follicular phase of the cycle. After the luteinizing hormone (LH) surge, growth of the follicle was more rapid. Concurrently, the follicle developed internal echogenicity with ultrasonic evidence of separation of the granulosa cell layer. The follicle was no longer visible 144 and 132 h after the LH rise and peak respectively. There was no primary progesterone rise associated with either the LH rise or peak, but a secondary progesterone rise occurred 42 h after the onset of the LH surge. Peri-follicular blood flow velocity was detected for the first time on cycle day 5 and appeared to rise after the onset of the LH surge. Peri-follicular blood flow velocity appeared to reduce after the LH surge to values associated with the follicular phase. These observations are consistent with an association of a primary granulosa cell defect with luteinized unruptured follicle syndrome which would account for the initial slow follicular growth, absent primary progesterone rise and reduction in blood flow in the wall of the follicle after the LH surge.

Adult↗

PubMed1996

Cell shape change reveals the cyclic AMP-mediated action of follicle stimulating hormone, human chorionic gonadotrophin and vasoactive intestinal peptide in primary cultured human granulosa-lutein cells.

Granulosa cells are known to be the site of action of various hormones and agents that regulate ovarian function. This study was conducted to evaluate the effects of gonadotrophins, vasoactive intestinal peptide (VIP), prostaglandin (PG) F2 alpha and angiotensin II on the cyclic AMP (c-AMP) signalling transduction pathway in human granulosa-lutein cells. Exposure to agents that elevate c-AMP or mimic c-AMP action caused the cells to become rounded in a process that was rapid and reversible. We were able to demonstrate this cell rounding process in the presence of gonadotrophins and VIP, but not in the presence of PGF 2 alpha or angiotensin II. In addition, incubation of the cells with various selective phosphodiesterase (PDE) inhibitors revealed that the PDE type IV isoform, but not type III, catalyses c-AMP degradation in human granulosa-lutein cells. Alteration in c-AMP-dependent cytomorphology appears to be a convenient method to analyse the regulation of c-AMP-mediated events in the human granulosa-lutein cells.

Adenosine Monophosphate↗

PubMed1991

Induction of ovulation in rabbits with pure urinary luteinizing hormone and human chorionic gonadotrophin: comparison of oocyte and embryo quality.

Thirty-six 18-week-old nulliparous does were stimulated with a single dose of 25 IU pregnant mare serum gonadotrophin (PMSG). Ovulation was induced 48 h later with 50 IU luteinizing hormone (LH) (18 does) or 50 IU human chorionic gonadotrophin (HCG) (18 does) in order to determine the effects of pure urinary LH and HCG on the quality of oocytes and embryos. Nine does were mated in each group. The does were slaughtered 24 h after induction of ovulation to recover oocytes and 48 h after mating to recover embryos. The number of haemorrhagic, preovulatory and luteinizing follicles per ovary were recorded. The quality of oocytes and embryos recovered were evaluated. No significant differences in the number of haemorrhagic follicles (blood follicles without stigma), preovulatory and luteinizing follicles were observed between LH and HCG groups. LH has a selective action, which could permit the acquisition of better quality oocytes. Although the fertilization rate was similar in both groups (LH versus HCG), the percentage of degenerate embryos (grade 5) was lower for the LH (3%) than the HCG (13%) groups.

Animals↗

PubMed1991

Effect of aspiration of the preovulatory follicle on luteinization, corpus luteum function, and peripheral plasma gonadotropin concentrations in the mare.

Follicular fluid from small- to medium-sized follicles has been shown to have an inhibiting effect on luteinization of granulosa cells in vitro. This study was conducted to investigate the effect of in vivo removal of follicular fluid on luteinization, peripheral gonadotropin concentrations, and ovulation of secondary follicles in the mare. Follicular fluid was aspirated from the preovulatory follicles of mares when the diameter of the follicle was 30-34 mm (Group A), 35-39 mm (Group B), or 40-44 mm (Group C). Mares in Group D served as controls and the preovulatory follicle was not aspirated. Mares in Group A had a significantly earlier rise in peripheral progesterone concentrations than did controls. There was no difference in duration of progesterone secretion or peak progesterone production between groups. LH and FSH values were significantly higher for mares in Groups A and B than for control mares. Mares in Group A tended to have a higher incidence of secondary ovulations than did mares in other groups. These data support the in vitro findings that follicular fluid from small- to medium-sized follicles may contain a luteinization inhibitor, and indicate that presence of follicular fluid during the final days of follicular maturation is not essential for development of a normal CL.

Animals↗

PubMed1997

A local oxytocin system is part of the luteinization process in the preovulatory follicle of the marmoset monkey (Callithrix jacchus).

Luteinization is a complex differentiation process involving the interaction of extrinsic and intraovarian factors. The aim of this study was to examine the components of an intraovarian oxytocin (OT) system during the periovulatory period in the marmoset monkey, as well as the possible relationship of these components to other factors involved in the luteinization process, using immunohistochemistry and cell culture techniques. Ovaries were collected on Day 7 of the follicular phase (before the endogenous LH surge) and on Day 8 (22 h after an exogenous hCG application, but before ovulation). Before the endogenous LH increase, OT immunoreactivity was detectable at low levels in most antral follicles, where its presence was confined to antral granulosa cell (GC) layers. In contrast, immunoreactivity for the OT receptor (OTR) was localized primarily in the basal GC layer. After application of exogenous hCG, there was a marked enhancement in both the staining intensity and the number of cells positive for OT and the OTR in all GC layers of antral follicles, especially in the preovulatory follicle. Progesterone receptor and 3beta-hydroxysteroid dehydrogenase activity in GC were clearly present only when follicles were obtained after gonadotropin stimulation. Secretion of authentic OT was demonstrated from cultured GC obtained before the LH surge, with highest amounts in cells cultured from preovulatory as opposed to smaller antral follicles. OT production could be stimulated by the application of hCG to the GC cultured from preovulatory follicles, whereas the gonadotropin was without effect on GC from small follicles. FSH had no effect on OT production by GC from either follicle type. Application of OT to the cultures caused an increase in progesterone production by GC from large preovulatory follicles but was without effect on steroidogenesis by cells from small antral follicles. These results describing the presence and distribution of OT and OTR and their modulation by hCG, as well as the luteotrophic effect of OT in cultured GC from preovulatory follicles, implicate OT as a paracrine mediator in the luteinization process in the primate ovary.

3-Hydroxysteroid Dehydrogenases↗

PubMed2005

Obesity, lutein metabolism, and age-related macular degeneration: a web of connections.

Age-related macular degeneration (AMD) is a major cause of visual impairment in the United States. Currently there is no effective cure for this disease. Risk factors include decreased lutein and zeaxanthin status and obesity. Obesity is also an increasing public health concern. The alarming increase in the prevalence of obesity further exacerbates the public health concern of AMD. The mechanism by which obesity increases the risk of AMD may be related to the physiologic changes that occur with this condition. These include increased oxidative stress, changes in the lipoprotein profile, and increased inflammation. These changes would also result in an increased destruction and a decreased circulatory delivery of lutein and zeaxanthin to the macula of the eye. Therefore, the mechanism by which obesity is related to AMD risk may be through indirect effects on changes in lutein and zeaxanthin status and metabolism.

Age Factors↗

PubMed2005

Dietary lutein and zeaxanthin: possible effects on visual function.

Of the many carotenoids circulating in human sera, only lutein and zeaxanthin are accumulated throughout the tissues of the eye. Within the eye, they reach their highest concentration in the central retina, where they are clinically referred to as the macula lutea. Lutein and zeaxanthin, more commonly referred to as macular pigments, may serve a variety of roles in the specialized vision of higher primates. This paper reviews recent studies investigating the influence of macular pigments on human visual performance. Such studies have offered insight into why lutein and zeaxanthin are uniquely concentrated in ocular tissues.

Antioxidants↗

PubMed1970

Prostaglandin receptor site: evidence for an essential role in the action of luteinizing hormone.

A dose-response relation was established between prostaglandins and formation of adenosine 3',5'-monophosphate in the mouse ovary. The prostaglandin antagonist, 7-oxa-13-prostynoic acid, blocked the stimulatory effect of prostaglandin E(1), prostaglandin E(2), and luteinizing hormone on adenosine 3',5'-monophosphate formation in a competitive manner. Kinetic studies made it possible to suggest that there is a single luteinizing-hormone-related prostaglandin receptor in mouse ovaries, and that activation of this prostaglandin receptor is an essential requirement in the action of luteinizing hormone to stimulate adenosine 3',5'-monophosphate formation and steroidogenesis.

Adenine↗

PubMed1971

Ovulation induced by synthetic luteinizing hormone-releasing hormone in the hamster.

A synthetic decapeptide, corresponding to the chemical structure of luteinizing hormone-releasing hormone from porcine hypothalami, was tested for the induction of ovulation in golden hamsters that had previously been treated with phenobarbital to prevent spontaneous ovulation. Subcutaneous injection of 0.089 to 0.357 nanomole of this synthetic luteinizing hormone-releasing hormone stimulated release of luteinizing hormone and induced ovulation.

Animals↗

PubMed1979

Release of luteinizing hormone in male mice during exposure to females: habituation of the response.

Male mice release luteinizing hormone when exposed for a short time to a female. In this experiment, multiple blood samples were withdrawn by atrial cannulas from tethered males during either continuous or intermittent exposure to nonreceptive females. After an immediate, transient release of luteinizing hormone, continuous exposure to the same female was accompanied by only random, spontaneous elevations in plasma levels of this hormone. Successive presentations of the same female at 2-hour intervals elicited gradually diminishing luteinizing hormone responses. Exposing such unresponsive males to novel, diestrous females, however, dramatically stimulated their release of the hormone. These results demonstrate habituation of a socially induced, neuroendocrine response involving reproductive hormones.

Animals↗

PubMed1982

Suppression of ovulation in the rat by an orally active antagonist of luteinizing hormone-releasing hormone.

A synthetic antagonist of luteinizing hormone-releasing hormone blocked ovulation in rats in a dose-dependent manner when given by gavage on the afternoon of proestrus. Ovulation was delayed for at least 1 day in all animals given 2 milligrams of antogonist and in some of the animals treated with 1 or 0.5 milligram. Oral administration of 2 milligrams also blocked the preovulatory surge of luteinizing hormone. This demonstration that antagonists of luteinizing hormone-releasing hormone can have oral antiovulatory activity clearly enhances their therapeutic potential.

Administration, Oral↗

PubMed1981

Male vole urine changes luteinizing hormone-releasing hormone and norepinephrine in female olfactory bulb.

Female prairie voles (Microtus ochrogaster) exposed to a single drop of male urine on the upper lip showed changes in concentrations of luteinizing hormone-releasing hormone (LHRH) and norepinephrine in olfactory bulb tissue; no such changes occurred in dopamine concentration. The changes were measured in the posterior but not the anterior olfactory bulb tissue of females within 1 hour after they were exposed to urine. These females also showed rapid increases in serum concentrations of luteinizing hormone. Females exposed to water on the upper lip showed none of these changes. These results suggest that in this species LHRH and norepinephrine in the olfactory bulb may mediate luteinizing hormone release in response to external (pheromonal) chemical cues.

Animals↗

PubMed1980

Classical conditioning: induction of luteinizing hormone and testosterone secretion in anticipation of sexual activity.

A classical conditioning paradigm was used to demonstrate that male rats can learn to secrete luteinizing hormone and testosterone in anticipation of sexual activity. Sexually naïve males were exposed to a neutral stimulus and then to a sexually receptive female once daily. After exposure to the paired stimuli for 14 trials, the neutral stimulus was as effective as the female in triggering luteinizing hormone and testosterone secretion. These findings provide two novel perspectives on the control of reproductive hormone secretion in male rats: (i) environmental cues, which males learn to associate with sexual activity, induce the secretion of hormones that regulate pituitary-testis function, and (ii) classical conditioning may be used as a noninvasive method to evoke functional alterations in the secretion of luteinizing hormone and presumably the neuroendocrine pathways that mediate its release.

Animals↗

PubMed1995

The 1994 Stevenson Award Lecture. Follicle-stimulating hormone and luteinizing hormone: a tale of two gonadotropins.

Although most gonadotropes synthesize both luteinizing hormone and follicle-stimulating hormone, the transcription, content, and secretion rates of the two gonadotropins can be separated. The signals external to the gonadotropic cells that appear to be important in the differential regulation are gonadotropin-releasing hormone pulse frequency (high pulse frequency favors luteinizing hormone), steroid feedback (works on both but induces a more powerful negative feedback on luteinizing hormone), and gonadal peptide feedback (activin increases follicle-stimulating hormone; inhibin and follistatin decrease it). We know very little about the pathways within the gonadotropes that favor one gonadotropin rather than another. It is expected that the cloning of the genes for both gonadotropins and the use of specific cell lines and transfections will lead to elucidation of these pathways.

Animals↗

PubMed2003

The role of nitric oxide on apoptosis in human luteinized granulosa cells. Immunocytochemical evidence.

This study was designed to investigate the role of nitric oxide (NO) on the apoptosis of human luteinized granulosa cells and its possible pathways. Granulosa cell suspensions were incubated for 48 h after adding NO donor (S-nitroso-N-acetyl-penicillamine, SNAP) and NO synthase inhibitor (nitro-L-arginine methyl ester, L-NAME) at different concentrations. Apoptosis was examined using a terminal deoxynucleotide-transferase-mediated dUTP-biotin nick end labeling method in 70 patients, and immunocytochemical staining was performed for six apoptosis-related proteins in 50 patients. Apoptotic rates were significantly lower in cells incubated with 0.5 mM SNAP, but higher with 0.5, 1.0, and 5.0 mM L-NAME. SNAP (0.5 mM) lowered the expression of Fas and p53 in luteinized granulosa cells, but Bcl-2 expression was increased, and Fas ligand or Bax remained unchanged. Using L-NAME (0.5 and 5.0 mM), the expression of p53 and Bax was increased, but Bcl-2 was unchanged. Fas/Fas ligands were also activated especially in 5.0 mM L-NAME. In conclusion, NO may inhibit apoptosis via decreased Fas and p53, and increased Bcl-2 expression in human luteinized granulosa cells.

Adult↗