The Determination of Efficacy of CircuCare on Blood Circulation and Metabolism: An Animal Model Study.

OBJECTIVES: To determine whether feeding CircuCare to rats improves blood circulation, metabolism, immune regulation, endocrine activity, and oxidative stress. METHODS: 28 eight-week-old male Sprague-Dawley rats were evenly randomized into control and experimental groups. The control group was fed with ordinary drinking water, while the experimental group was fed with CircuCare at a daily dose of 93.75 mg per 300 g of body weight over eight weeks. Both groups were subjected to a swimming test, and blood samples were taken to observe any variations in various biochemical parameters before and after the test. Key Findings. The experimental group's mean swimming exhaustion duration was 53.2% longer and had a significantly higher lactic acid removal ratio. Their mean prostaglandin E2 level and mean glucose, cortisol, and glutathione level (30 minutes after swimming test) were also significantly higher. No undesirable impacts from CircuCare relating to general blood biochemistry values and bone mineral density were reported. CONCLUSIONS: The present results show that CircuCare can be safely used to increase stamina and exercise capability, expedite the metabolism of lactic acid, accelerate muscle repair, and promote the antioxidant activity of cells in rats.

[Body composition, mineral metabolism, and endocrine function of adipose tissue: influence of a nutritional supplement of propolis]. / Composición corporal, metabolismo mineral y función endocrina del tejido adiposo: influencia de un suplemento nutricional de propóleo.

INTRODUCTION: Introduction: propolis and its components influence lipid metabolism; however, its effect on body composition and mineral metabolism remains unknown. Objectives: to determine the effect of natural propolis supplementation on body composition, mineral metabolism, and the endocrine function of adipose tissue. Material and methods: twenty albino male Wistar rats (8 weeks old) were divided into two groups of 10 animals each. The rats were fed two different types of diet for 90 days: a standard diet for the control group (group C) and the same standard diet + 2 % propolis (group P). Thyroid hormones, ghrelin, leptin, adiponectin and insulin, non-esterified fatty acids (NEFA) in plasma, body composition (lean mass, fat mass and body water), and mineral deposition in target organs (spleen, brain, heart, lungs, testicles, kidneys and femur) were assessed. Results: thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) did not show any differences after supplementation with propolis, while ghrelin and adiponectin decreased (p < 0.01 and p < 0.05, respectively) and insulin (p < 0.01), leptin (p < 0.05) and NEFA (p < 0.05) increased when 2 % propolis was supplied, while weight and body fat were reduced (p < 0.05) and lean mass increased. Lastly, the propolis supplement improves calcium deposition in the spleen, lungs, testes, and femur (p < 0.05). Conclusion: propolis supplementation of the diet (2 %) causes a decrease in the secretion of ghrelin and adiponectin, increasing the release of non-esterified fatty acids and the rate of insulin secretion. In addition, propolis supplementation induces an improvement in calcium deposition in target organs without affecting the rest of minerals, which improves body composition by inducing a reduction in weight and visceral adipose tissue, and improvement in lean mass.

INTRODUCCIÓN: Introducción: el propóleo y sus componentes influyen en el metabolismo lipídico; sin embargo, se desconoce su efecto sobre la composición corporal y el metabolismo mineral. Objetivos: determinar el efecto de la suplementación de la dieta con propóleo natural sobre la composición corporal, el metabolismo basal y mineral, y la función endocrina del tejido adiposo. Material y métodos: veinte ratas albinas Wistar macho (8 semanas) se dividieron en dos grupos de 10 animales cada uno. Las ratas fueron alimentadas con dos tipos diferentes de dietas durante 90 días: una dieta estándar para el grupo de control (grupo C) y la misma dieta estándar + un 2 % de propóleo (grupo P). Se determinaron las hormonas tiroideas, la grelina, la leptina, la adiponectina y la insulina, los ácidos grasos no esterificados (AGNE) en el plasma, la composición corporal (masa magra, masa grasa y agua corporal) y el depósito de minerales en órganos diana (bazo, cerebro, corazón, pulmones, testículos, riñones y fémur). Resultados: los niveles plasmáticos de hormona estimulante del tiroides (TSH), triyodotironina (T3) y tiroxina (T4) no mostraron diferencias tras la ingesta del suplemento de propóleo, mientras que los de grelina y adiponectina disminuyeron (p < 0,01 y p < 0,05, respectivamente) y los de insulina (p < 0,01), leptina (p < 0,05) y AGNE (p < 0,05) aumentaron cuando la dieta se suplementó con propóleo al 2 %. Se redujeron el peso y la grasa corporal (p < 0,05), incrementándose la masa magra. Por último, el suplemento de propóleo mejoró el depósito de calcio en el bazo, los pulmones, los testículos y el fémur (p < 0,05). Conclusión: el suplemento de propóleo al 2 % de la dieta produjo una disminución de la secreción de grelina y adiponectina, incrementando la concentración de AGNE y aumentando la tasa de secreción de insulina. Además, el suplemento de propóleo indujo una mejora del depósito de calcio en los órganos diana sin afectar al resto de minerales, lo que en conjunto mejora la composición corporal al inducir una reducción del peso y del tejido adiposo visceral, mejorando la masa magra.

An F1-extended one-generation reproductive toxicity study in Crl:CD(SD) rats with 2,4-dichlorophenoxyacetic acid.

2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10-12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The "No Observed Adverse Effect Level" for systemic toxicity was 300 ppm in both males (16.6 mg/kg/day) and females (20.6 mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies.

Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats.

Stress and/or antidepressants during pregnancy have been implicated in a wide range of long-term effects in the offspring. We investigated the long-term effects of prenatal stress and/or clinically relevant antidepressant exposure on male adult offspring in a model of the pharmacotherapy of maternal depression. Female Sprague-Dawley rats were implanted with osmotic minipumps that delivered clinically relevant exposure to the antidepressant escitalopram throughout gestation. Subsequently, pregnant females were exposed on gestational days 10-20 to a chronic unpredictable mild stress paradigm. The male offspring were analyzed in adulthood. Baseline physiological measurements were largely unaltered by prenatal manipulations. Behavioral characterization of the male offspring, with or without pre-exposure to an acute stressor, did not reveal any group differences. Prenatal stress exposure resulted in a faster return towards baseline following the peak response to an acute restraint stressor, but not an airpuff startle stressor, in adulthood. Microarray analysis of the hippocampus and hypothalamus comparing all treatment groups revealed no significantly-altered transcripts. Real time PCR of the hippocampus confirmed that several transcripts in the CRFergic, serotonergic, and neural plasticity pathways were unaffected by prenatal exposures. This stress model of maternal depression and its treatment indicate that escitalopram use and/or stress during pregnancy produced no alterations in our measures of male adult behavior or the transcriptome, however prenatal stress exposure resulted in some evidence for increased glucocorticoid negative feedback following an acute restraint stress. Study design should be carefully considered before implications for human health are ascribed to prenatal exposure to stress or antidepressant medication.

A family with Camurati-Engelman disease. The role of the missense p.R218C mutation in TGFB1 in bones and endocrine glands.

OBJECTIVES: Camurati-Engelmann disease (CED) is a rare form of progressive bone dysplasia due to mutations in the transforming factor gene TGFB1 on chromosome 19q13.1-q13.3. Endocrine complications such as osteoporosis, vitamin D deficiency, delayed puberty and hypogonadotrophic hypogonadism may be present. METHODS AND RESULTS: Genetic analysis of the TGFB1 gene revealed a heterozygous missense mutation p.R218C in exon 4 of chromosome 19q13.1-q13.3 in a 14-year-old girl who presented with typical symptoms of CED, hyperprolactinaemia and menstrual irregularity. The patient responded well to prednisone 5 mg/kg per day as well as calcium and vitamin D supplements. CONCLUSIONS: The role of p.R218C in TGFB1 on the mechanism of the disease itself and the complications of it in bones and endocrine glands remain unclear. Early recognition as well as a detailed understanding of the pathogenesis of the disease is important for future treatment options and better quality of life of such patients.

Nitric oxide mediated effects on reproductive toxicity caused by carbon disulfide in male rats.

This study investigated nitric oxide (NO) mediation of carbon disulfide (CS(2)) toxicity that compromised male rat spermatogenesis and endocrine function. Rats were exposed to multiple levels of CS(2) concentration (0, 50, 250, 1250 mg/m(3)). A 1250 mg/m(3) CS(2)+sodium nitroprusside (SNP) group and a 1250 mg/m(3) CS(2)+NG-monomethyl-L-arginine (L-NMMA) group were established to explore the role of NO in mediating CS(2) toxicity. NO concentrations, NO synthase (NOS) activity, and sex hormone levels were measured, and sperm characteristics were observed and analyzed. Our data show that CS(2) exposure decreased: NOS activity; tissue NO concentrations; serum levels of gonadotropin-releasing hormones, luteinizing hormones, and testosterone; and sperm count and activity. In contrast, increased serum follicle-stimulating hormone concentrations and teratospermia were observed with CS(2) exposure. SNP reduced some of the toxic effects of CS(2), while L-NMMA treatment showed no effect. The results suggests that NO mediates compromised reproductive system function caused by CS(2) exposure.

The effects of arachidonic acid on the endocrine and osmoregulatory response of tilapia (Oreochromis mossambicus) acclimated to seawater and subjected to confinement stress.

In previous studies in freshwater tilapia (Oreochromis mossambicus), dietary supplementation with arachidonic acid (ArA; 20:4n - 6) had considerable, opposing effects on the main ion-transporting enzyme Na(+)/K(+)-ATPase in gills and kidneys and changed the release of osmoregulatory hormones, such as cortisol. The present study was performed to assess the influence of dietary ArA on (1) the osmoregulatory capacity of tilapia acclimated to seawater (SW) (34‰) and (2) the osmoregulatory imbalance associated with acute stress. The increased ambient salinity was associated with significant alterations in the tissue fatty acid composition, particularly the n - 6 polyunsaturated fatty acids (PUFAs). Tissue levels of ArA were further increased as a result of dietary supplementation, whereas docosahexaenoic acid (DHA, 22:6n - 3) and eicosapentaenoic acid (EPA, 20:5n - 3) decreased in gills and kidneys. Basal plasma cortisol as well as lactate levels were elevated in the ArA-supplemented SW-acclimated tilapia compared with the control group. The 5 min of confinement (transient stress) increased plasma cortisol, glucose, and lactate levels with significantly higher levels in ArA-supplemented tilapia. Confinement was also associated with significantly elevated plasma osmolality, sodium, chloride, and potassium levels. ArA-supplemented tilapia showed markedly lower ionic disturbances after confinement, suggesting that dietary ArA can attenuate the hydromineral imbalance associated with acute stress. These results emphasize the involvement of ArA and/or its metabolites in the endocrine and osmoregulatory processes and the response to confinement stress.

Physiological and therapeutical roles of ginger and turmeric on endocrine functions.

The natural product ginger (Zingiber officinale) has active constituents gingerol, Shogaol and Zerumbone, while turmeric (Curcuma longa) contains three active major curcuminoids, namely, curcumin, demethoxycurcumin, and bisdemethoxycurcumin. They have the same scientific classification and are reported to have anti-inflammatory and many therapeutic effects. This article reviews the physiological and therapeutic effects of ginger and turmeric on some endocrine gland functions, and signal pathways involved to mediate their actions. With some systems and adipose tissue, ginger and turmeric exert their actions through some/all of the following signals or molecular mechanisms: (1) through reduction of high levels of some hormones (as: T4, leptin) or interaction with hormone receptors; (2) by inhibition of cytokines/adipokine expression; (3) acting as a potent inhibitor of reactive oxygen species (ROS)-generating enzymes, which play an essential role between inflammation and progression of diseases; (4) mediation of their effects through the inhibition of signaling transcription factors; and/or (5) decrease the proliferative potent by down-regulation of antiapoptotic genes, which may suppress tumor promotion by blocking signal transduction pathways in the target cells. These multiple mechanisms of protection against inflammation and oxidative damage make ginger and curcumin particularly promising natural agents in fighting the ravages of aging and degenerative diseases, and need to be paid more attention by studies.

Influences of carbohydrate plus amino acid supplementation on differing exercise intensity adaptations in older persons: skeletal muscle and endocrine responses.

Losses in physiological function in healthy ageing occur partly as a consequence of reduced protein intake and partly as a consequence of less than 30-min/day of moderate to vigorous physical activity. The current study aimed to compare the effects of two different intensities of resistance training in healthy older adults, whose habitual dietary intake was supplemented with carbohydrate and amino acid preparations. We hypothesised that although intensive exercise with appropriate carbohydrate and amino acid supplementation would result in the most profound impact on in vivo markers of healthy physiologic and endocrine functions in previously sedentary older individuals, the effectiveness of the less intense exercise prescription with supplementation would also result in beneficial adaptations over and above findings of previous studies on low intensity exercise alone. Twenty-nine older adults (out of 32) completed the study after being randomly assigned to low (SUP_LowR, i.e., approximately 40% 1RM; n = 16) versus high resistance training (SUP_HighR, i.e., approximately 80% 1RM; n = 13) for 12 weeks. A carbohydrate supplement was ingested immediately before and during every exercise session and an amino acid cocktail was ingested post-exercise. Neither intervention significantly impacted upon body composition assessed using: Body mass index, waist/hip ratio and bioelectric impedance. Muscle strength increased similarly in the two groups with the SUP_HighR protocol showing 46 +/- 8%, 10.8 +/- 4.4% and 26.9 +/- 4.9% (P < 0.01) improvements in 1-RM strength, unilateral and bilateral knee extension torque, respectively, compared with 39 +/- 2%, 9.4 +/- 3.7% and 29.5 +/- 8.2% (P < 0.01) increments in the same measures in the SUP_LowR group. Lean muscle thickness however, showed a greater benefit of the SUP_LowR protocol (8.7 +/- 3.9% increase, P < 0.05) compared with the SUP_HighR protocol, which elicited no significant change. In terms of functional abilities, only the standing-from-lying (SFL) test exhibited an improvement in rate in the SUP_HighR group (-11.4%, P < 0.05). The SUP_LowR group, on the other hand, showed significant improvements in the get-up-and-go (-8.7 +/- 3.6%, P < 0.05), the SFL (-4.7% change, P = 0.05) and the 6-min walk (7.2 +/- 2.2% increase in distance covered, P < 0.01) tests. Following overnight fasting, serum levels of glucose changed significantly (-13 +/- 4.7% decrease, P < 0.01) in SUP_LowR. Serum levels of insulin (-25 +/- 5.3% decrease, P = 0.05), neuropeptide Y (-24 +/- 15.3% decrease, P = 0.02), and IGFBP-3 (-11 +/- 6.6% decrease, P = 0.03), changed significantly in SUP_HighR. Circulating levels of interleukin-6, tumour necrosis factor-alpha and insulin-like growth factor 1 did not alter significantly in either intervention group. These data suggest that whilst both interventions were beneficial in older persons, the end targets as well as metabolic and hormonal adaptations are different. The supplementation plus low exercise regimen tended to impact on muscle hypertrophy combined with increased habitual function. Supplementation plus high-intensity exercise regimen improved markers of strength, but not to a significantly greater extent than supplementation plus low intensity exercise.

Morphophysiology of endocrine glands in young hogs during postnatal ontogeny under conditions of treatment with biogenic compounds.

Combined trepel+suvar or trepel+polystim treatment of young hogs under biogeochemical conditions of the Chuvash Center ecological subregion stimulates structural and functional organization of the thymus and thyroid and adrenal glands and is therefore physiologically justified.

A new database for food safety: EDID (Endocrine disrupting chemicals - Diet Interaction Database).

Diet is a significant source of exposure to endocrine disrupting chemicals (EDC); health risks cannot be excluded, in particular long-term effects in vulnerable Groups such as children. However, food safety assessment must also consider the effects of natural food components modulating the endocrine system. The scientific evidence on the complex interactions between EDC and food components is still limited. The new EDC-Diet Interactions Database (EDID) within the ISS EDC area (www.iss.it/inte/) aims to stimulate further research in the field of food toxicology: a database on international literature's studies, either on experimental systems and on animal population and humans, easy to consult and periodically updated. Examples of studies contained in EDID are provided concerning EDC with iodine, vitamins and phytoestrogens.

Differential endocrine response in rams to intracerebroventricular infusion of genistein.

The intracerebroventricular infusions of genistein (total 40 mug) were made in male sheep (November) to test its influence on melatonin, growth hormone (GH) and luteinizing hormone (LH) secretion. The analysis of the results encompassed 3 similar periods: before the infusion (afternoon hours) the first (evening hours) and the second (night hours) halves of the treatment. The night plasma concentration of melatonin in genistein-infused rams was significantly lower than that noted during the respective period in vehicle-infused rams. Plasma GH concentration increased significantly in both vehicle- and genistein-infused rams during the night hours, as compared with the concentrations noted during the afternoon and evening, however, genistein significantly stimulated the amplitude of GH pulses in these latter. The LH concentration was significantly lower during the second part of genistein treatment, than in vehicle-infused rams. The frequency and amplitude of LH pulses clearly tended to decrease following genistein infusion. In conclusion, genistein, acting at the central nervous system level in sexually active rams is able to reduce the secretion of melatonin and LH and has also a slight stimulatory effect on the amplitude of GH pulses.

Initial study on the effects of Prestige oil on human health.

The big oil tanker Prestige wrecked at 130 miles from the coast of Galicia, on the Northwest of Spain, in November 19, 2002. During the accident over 40,000 tons of oil were spilled, and along the next weeks 22,000 more reached the shore in the way of three black tides. A great number of people participated in the cleaning tasks. The objective of this study was to initially evaluate the damage caused by Prestige oil in exposed individuals both from the cytogenetic and the endocrine points of view. Exposure level was determined by analysing volatile organic compounds in the environment and heavy metals in blood. Cytogenetic damage was determined by sister chromatid exchanges (SCE), and plasmatic prolactin and cortisol levels were used as biomarkers of endocrine toxicity. Finally we have determined the possible influence of GST genetic polymorphisms (GSTM1 and GSTT1 deletion polymorphisms, GSTP1 Ala105Val) on the evaluated effects. The exposed population was classified according to the performed cleaning tasks in three groups: volunteers that collaborated for 1 week (N=25), hired manual workers (N=20) and hired high-pressure cleaner workers (N=23). The control population consisted of 42 individuals. Exposure to Prestige oil caused cytogenetic damage in exposed individuals, being its effect influenced by age, sex, tobacco consumption and GSTM1 polymorphism. With regard to endocrine toxicity, our results showed that xenobiotics present in Prestige oil induced alterations in hormonal status, and thus it may be considered as an endocrine disruptor. Therefore, the selected parameters have shown to be good indicators of toxicity related to exposure to Prestige oil. In addition, data obtained point to the importance of using protective devices in preventing the effects related to the exposure.

Integrated risk assessment and endocrine disrupters.

1. The procedures currently employed for risk assessment are unlikely to be sustainable in the future for a variety of reasons. A number of actions are needed to remedy the situation and the most important of these actions are: * to improve access to existing data; * to introduce a prioritisation system based on exposure assessment; * to co-ordinate and harmonise approaches of different organisations involved in risk assessment. 2. Integration of information and methodologies between human health risk assessment and ecological risk assessment (integrated risk assessment) is advocated in this paper as one of the most important steps towards a holistic and effective way of conducting a risk assessment. 3. A framework is proposed for identification of agents for which an integrated risk assessment would be of particular value. Close collaboration across disciplines and across countries is necessary for the potential of integrated risk assessment to be realised in practice. The practicality of applying integrated risk assessment to endocrine disrupting agents is presently being investigated in an EU funded multi-laboratory collaborative study (CREDO).

Behavioral effects of endocrine-disrupting substances: phytoestrogens.

A major source of endocrine-disrupting substances, usually not considered in laboratory animal experiments, is the diet used in research investigations. Soy represents the main protein source in almost all natural-ingredient commercially available formulated diets. Soy-derived isoflavones are the most abundant and in many ways the most studied phytoestrogens, and phytoestrogens (isoflavones) are known endocrine disruptors. Research is reviewed that identifies the physiological and behavioral endocrine-disrupting effects of dietary phytoestrogens (isoflavones) in animal diets, including most of the isoflavones, which are in a glycoside form and biologically inactive, and those in the gastrointestinal tract, which are biologically active. The isoflavones genistein and daidzein have similar molecular weights and structural characteristics to that of 17-beta estradiol, which may enable them to exert estrogenic and antiestrogenic properties are described and characterized. Daidzein can be further metabolized to the potent and abundant molecule equol, which in rodents is produced in very large amounts and represents the major circulating metabolite among all biologically active isoflavones. Equol has the unique and important ability to specifically bind 5 alpha-dihydro-testosterone, and to act in turn to inhibit the action of this potent androgen. The specific influence of dietary soy phytoestrogens on consumptive, learning and memory, and anxiety-related behaviors is identified. Regulatory behaviors such as food and water intake, adipose deposition and leptin, and insulin levels affected by dietary isoflavones are also discussed.

Phytoestrogen genistein and its pharmacological interactions with synthetic endocrine-active compounds.

Phytoestrogens are plant-derived compounds with estrogen-like activities. Certain foods such as soy-derived products are known to have high levels of phytoestrogens, and about 25% of commercial infant formulas used in the United States are soy-based. One of the most important phytoestrogens is the isoflavone genistein. Human exposures to genistein occur through normal dietary intake and through the use of genistein or other isoflavone extracts as nutritional supplements. Among the issues raising concerns about human exposure to phytoestrogens is how such exposure may affect responsiveness and sensitivity of the exposed subjects to other xenobiotics, particularly drugs and environmental chemicals with estrogenic or other endocrine activities. This article describes our recent studies on the developmental effects of dietary genistein in rats and its potential to interact with the toxicology of the endocrine-active pesticide methoxychlor. Data from our studies demonstrated that genistein is capable of altering the toxicological behaviors of methoxychlor and likely other endocrine active compounds as well. The complexities of such interactions are difficult to predict based on their in vitro steroid receptor reactivities.

One-step analysis of testis steroidogenesis from neonatal exposure to synthetic estrogen by normal-phase HPLC.

Neonatal exposure to synthetic estrogen endocrine disruptors or estrogen-receptor inhibitors induces developmental abnormalities in the male reproductive system. To investigate whether neonatal exposure affects spermatogenesis in juvenile and pubertal testis, Sprague-Dawley rat pups were given synthetic estrogen endocrine disruptors or estrogen-receptor inhibitors by a single injection on the day of birth at concentrations ranging between 2 to 40 mm, and sacrificed on day 21 (juvenile), 35 (prepuberty) or 50 (puberty). The testes were weighed and examined histologically at each stage. Further, the metabolites of steroidogenesis were analyzed using normal-phase high performance liquid chromatography. Neonatal exposure significantly reduced testis weights and steroidogenesis to one- fifth to one-half of that of the juvenile control, and further suppressed irreversible steroidogenesis and spermatogenesis during puberty.

Endocrine disruption by cadmium, a common environmental toxicant with paradoxical effects on reproduction.

Cadmium (Cd(2+)) is a common environmental pollutant and a major constituent of tobacco smoke. Exposure to this heavy metal, which has no known beneficial physiological role, has been linked to a wide range of detrimental effects on mammalian reproduction. Intriguingly, depending on the identity of the steroidogenic tissue involved and the dosage used, it has been reported to either enhance or inhibit the biosynthesis of progesterone, a hormone that is inexorably linked to both normal ovarian cyclicity and the maintenance of pregnancy. Thus, Cd(2+) has been shown to exert significant effects on ovarian and reproductive tract morphology, with extremely low dosages reported to stimulate ovarian luteal progesterone biosynthesis and high dosages inhibiting it. In addition, Cd(2+) exposure during human pregnancy has been linked to decreased birth weights and premature birth, with the enhanced levels of placental Cd(2+) resulting from maternal exposure to industrial wastes or tobacco smoke being associated with decreased progesterone biosynthesis by the placental trophoblast. The stimulatory effects of Cd(2+) on ovarian progesterone synthesis, as revealed by the results of studies using stable porcine granulosa cells, appear centered on the enhanced conversion of cholesterol to pregnenolone by the cytochrome P450 side chain cleavage (P450scc). However, in the placenta, the Cd(2+)-induced decline in progesterone synthesis is commensurate with a decrease in P450scc. Additionally, placental low-density lipoprotein receptor (LDL-R) mRNA declines in response to Cd(2+) exposure, suggesting an inhibition in the pathway that provides cholesterol precursor from the maternal peripheral circulation. Potential mechanisms by which Cd(2+) may affect steroidogenesis include interference with the DNA binding zinc (Zn(2+))-finger motif through the substitution of Cd(2+) for Zn(2+) or by taking on the role of an endocrine disrupting chemical (EDC) that could mimic or inhibit the actions of endogenous estrogens. Divergent, tissue-specific (ovary vs. placenta) effects of Cd(2+) also cannot be ruled out. Therefore, in consideration of the data currently available and in light of the potentially serious consequences of environmental Cd(2+) exposure to human reproduction, we propose that priority should be given to studies dedicated to further elucidating the mechanisms involved.

Dietary influence on the impact of ethinylestradiol-induced alterations in the endocrine/reproductive system with perinatal maternal exposure.

We investigated the effects of two diets, differing in phytoestrogen contents, on the phenotypic changes induced in the endocrine/reproductive system by perinatal exposure to an estrogen agonist during a critical period for brain sexual differentiation in rats. Ethinylestradiol (EE) was mixed at a concentration of 0.5 ppm into two diets: CRF-1, a standard rodent diet containing soybean-derived phytoestrogens; and a soy-free (SF) diet. These diets were provided to maternal Sprague-Dawley rats during gestational day 15 to postnatal day 10. Growth suppression of offspring was evident with EE especially during the exposure period and was slightly enhanced with the SF diet. On the other hand, most of the female offspring exposed to EE with CRF-1 showed early onset of vaginal opening, strong irregularity in estrous cycle (persistent estrus) and profound histopathological alterations, such as multifollicular ovaries, endometrial hypertrophy, and diffuse hyperplasia of the anterior pituitary. These EE-induced changes were much less pronounced with the SF diet. The results thus demonstrated differential effects of perinatal EE depending on the basal diet used, with enhancement of typical estrogenic responses in females by potential soybean-derived factor(s).

Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome.

Effects of a polyunsaturated fatty acid (PUFA)-rich diet were investigated in 17 polycystic ovary syndrome (PCOS) patients. After a 3-month habitual diet period, dietary fats were partly replaced with PUFAs for another 3 months. The PUFA-rich diet increased plasma linoleic acid from 28.36 +/- 1.00% to 33.76 +/- 1.08% (P < 0.002) and alpha-linolenic acid from 0.52 +/- 0.03% to 1.06 +/- 0.10% (P < 0.0001). Fasting glucose increased from 76 +/- 3 to 95 +/- 3 mg/dl (4.2 +/- 0.2 to 5.30.2 mmol/liter; P < 0.0001), and the area under the curve for glucose during oral glucose tolerance test increased from 421 +/- 34 to 503 +/- 31 mg/dl (23.4 +/- 1.9 to 27.9 +/- 1.7 mmol/liter; P < 0.001). Plasma insulin did not change either at fasting or during oral glucose tolerance test. Fasting plasma free fatty acids decreased from 0.596 +/- 0.048 to 0.445 +/- 0.058 mg/dl (P = 0.037), and ketone bodies decreased from 9.14 +/- 1.57 to 3.63 +/- 0.62 mg/dl (895 +/- 154 to 356 +/- 61 micromol/liter; P < 0.003). Plasma 15-deoxyprostaglandin J(2) tended to decrease (from 239 +/- 65 to 171 +/- 60 ng/ml; P = 0.053). Plasma testosterone, free testosterone, SHBG, dehydroepiandrosterone sulfate, LH, FSH, and urinary estrogen conjugates did not change. Urinary pregnanediol 3-glucuronide increased from 18.6 +/- 2.2 to 31.0 +/- 5.7 micro g/mg creatinine (P = 0.038). In conclusion, increased dietary PUFA intake can exert significant metabolic and endocrine effects in women with PCOS.