Effects of Dietary Chromium Methionine on Growth Performance, Carcass Composition, Meat Colour and Expression of the Colour-related Gene Myoglobin of Growing-finishing Pigs.

To investigate the effect of dietary chromium (Cr) as Cr methionine (CrMet) on growth performance, carcass traits, pork quality, meat colour and expression of meat colour-related genes in growing-finishing pigs, 189 crossbred Duroc×(Landrace×Yorkshire) growing-finishing pigs (male, castrated, average initial BW 74.58±1.52 kg) were selected and randomly allocated into four groups. Dietary treatments per kg of feed were as follows: 0 (CT), 0.3 mg/kg (T1), 0.6 mg/kg (T2) and 0.9 mg/kg (T3) Cr (in the form of CrMet; as-fed basis), and each treatment was replicated five times with 8 to 10 pigs per replicate pen. During the 28 d of the experiment, both the ADG and the ADFI increased linearly (p<0.05) as the level of dietary Cr increased. The F/G ratio decreased linearly (p<0.05). As dietary Cr increased, loin muscle areas (linear, p = 0.013) and average backfat thickness (linear, p = 0.072) decreased. Shear force (linear, p = 0.070) and Commission Internationale de I'Éclairage (CIE) redness (quadratic, p = 0.028) were increased. In addition, CIE Lightness (quadratic, p = 0.053) were decreased as dietary Cr increased. As dietary Cr increased, total myglobin (Mb) content (quadratic, p = 0.015) and the mb mRNA levels (quadratic, p = 0.046) in longissimus muscles of pigs were up-regulated. In conclusion, supplementation of dietary Cr improved growth and meat colour, but increased shear force and decreased IMF reduced palatability of longissimus muscles. Moreover, the increasing total Mb content and mb mRNA levels indicated that CrMet dietary supplementation may improve meat colour via up-regulating expression of the mb gene.

Estrogenic soybean isoflavones and chronic disease Risks and benefits.

Many edible plants contain natural estrogens called phytoestrogens. These compounds possess mixed estrogen agonist-antagonist properties that are organ-specific in vivo. We have focused on estrogenic soybean isoflavones because of their potential extensive dietary availability. In this article, we review the clinical and experimental evidence for the possible benefits and risks of ingestion of estrogenic isoflavones throughout the life span, and highlight areas needing further elucidation.

The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects.

In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women's health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan.

Immunoglobulin G subclass deficiency and susceptibility to pyogenic infections in patients with AIDS-related complex and AIDS.

Total immunoglobulin (Ig) and IgG subclass levels were measured in 72 patients with AIDS or AIDS-related complex (ARC). IgG2 subclass levels were found to be significantly decreased in the AIDS/ARC patients with pyogenic infections compared with both similar individuals without bacterial disease and the HIV-negative control group.

Delta 9-tetrahydrocannabinol suppression of prolactin secretion in the rat: lack of direct pituitary effect.

The effects of (--)trans-delta 9-tetrahydrocannabinol (THC) on tonic PRL secretion were investigated in long term ovariectomized or hypophysectomized/pituitary-autografted female rats and in flask incubations of anterior pituitary tissue. Intravenous injection of 0.25-8.0 mg THC/kg BW into ovariectomized rats markedly suppressed serum PRL 60 min later relative to control PRL levels. In a second experiment, ovariectomized rats bearing intraatrial cannulae were injected with 0.5 mg THC/kg BW, iv, and serial blood samples were drawn. PRL was significantly suppressed at 10 min, with persistence of the suppression for the duration of the 70-min sampling period in this time-course study. In contrast, the administration of 1.0 mg THC/kg BW, iv, to hypophysectomized/pituitary-autografted female rats failed to influence PRL secretion throughout a 120-min posttreatment sampling period. The apparent inability of THC to directly suppress PRL release from pituitary tissue was further studied by in vitro flask incubations of anterior pituitary tissue. Although a 1-h exposure of rat anterior pituitary tissue to bromocryptine (CB-154; 2.2 X 10(-4) M) suppressed subsequent PRL release, similar exposure to 10(-6) or 10(-4) M THC had no influence. The failure of THC to alter tonic PRL secretion in hypophysectomized/pituitary-autografted rts or PRL release from pituitary tissue in vitro strongly suggests that the central nervous system rather than the pituitary is the site of THC action in the acute suppression of tonic PRL secretion.

Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone.

Lactoferrin (LTF), an iron-binding glycoprotein present in most exocrine secretions and in the secondary granules of polymorphonuclear leucocytes (PMN), is regulated by estrogen in the mouse reproductive tract. We investigated the expression of LTF mRNA and protein during the natural estrous cycle to increase our understanding of how this uterine secretory protein is regulated under physiological conditions. There was a positive correlation between LTF mRNA expression in the genital tract and serum estradiol (E2) concentrations. When E2 peaked in proestrus, LTF mRNA and protein were expressed in the uterus; however, during metestrus, when both E2 and progesterone levels were high, LTF mRNA was expressed, while LTF protein was decreasing. LTF protein expression may be hindered by progesterone or some other local factor in the endometrial epithelium after ovulation. Immunohistochemistry demonstrated two distinct staining patterns for LTF in the vaginal and endometrial epithelium. In one staining pattern, the colorimetric reaction was noted over the cytoplasm, and in the other, the nuclear region stained more intensely. This suggests the possibility that in addition to its known role as a secretory protein, LTF may be transported to the nucleus, serving an autocrine role. Our results also indicated that LTF protein is a useful marker for tracking PMN. Nonproliferating epithelial cells in the vagina and endometrium may synthesize chemotactic and/or adhesion molecules for PMN.

The effect of leuprolide acetate on ovulation induction with human menopausal gonadotropins in polycystic ovary syndrome.

The use of exogenous gonadotropins for treatment of clomiphene-resistant chronic anovulation in women with the polycystic ovary syndrome (PCO) is hazardous and often ineffective, possibly because of the abnormal endogenous gonadotropin secretion characteristic of PCO. We evaluated the effect of leuprolide acetate, a long-acting GnRH agonist, on serum gonadotropin and sex steroid concentrations before and during human menopausal gonadotropin (hMG) induction of ovulation in women with PCO. In this controlled prospective randomized study, leuprolide was administered daily for 4 weeks, followed by concomitant hMG administration. Gonadotropin and steroid hormone concentrations were compared with those during ovulation induction cycles in women with PCO receiving hMG only. Daily administration of leuprolide for 4 weeks resulted in significantly decreased serum LH, estradiol, and testosterone concentrations, but no change in serum progesterone, FSH, and dehydroepiandrosterone sulfate. Compared to ovulation induction using hMG alone, leuprolide administration before and during hMG treatment prevented preovulatory rises in serum LH and P concentrations, while having no effect on serum FSH, testosterone, estradiol, and dehydroepiandrosterone sulfate. We conclude that leuprolide administered to women with PCO decreases gonadal steroid production and is capable of preventing premature luteinization during hMG induction of ovulation.

Fasting and postprandial lipid abnormalities in hypopituitary women receiving conventional replacement therapy.

Hypopituitary patients, particularly women, have excess mortality, mostly due to vascular disease. We have studied circulating lipid and lipoprotein concentrations, fasting and over 24 h, in hypopituitary women and men and in matched controls. Firstly, 67 hypopituitary patients (36 women) and 87 normal controls (54 women) were studied after an overnight fast. Secondly, 12 patients (6 women) and 14 matched controls (7 women) were studied over 24 h of normal meals and activity. The patients were all GH deficient and were replaced with cortisol, T4, and sex hormones where appropriate, but not with GH. In the first study, circulating triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol were measured after an overnight fast. In the second study, fasting levels of apolipoprotein B, apolipoprotein A1, and lipoprotein(a) were also measured, and then circulating triglyceride and total cholesterol concentrations were measured over 24 h. Fasting concentrations of triglyceride (mean +/- SEM, 1.73 +/- 0.22 vs. 1.11 +/- 0.09 mmol/L; P = 0.0025), total cholesterol (6.45 +/- 0.25 vs. 5.59 +/- 0.21 mmol/L; P = 0.002), LDL cholesterol (4.58 +/- 0.24 vs. 3.80 +/- 0.19 mmol/L; P = 0.007), and apolipoprotein B (135 +/- 10 vs. 111 +/- 9 mg/dL; P = 0.048) were elevated in hypopituitary compared to control women. The lipid alterations were observed in older and younger women and occurred independently of sex hormone or glucocorticoid replacement. Fasting values were not significantly different in hypopituitary and control men. Patients and controls (women and men) had similar fasting HDL cholesterol, apolipoprotein A1, and lipoprotein(a) concentrations. Although the differences that existed in fasting lipid values were most marked in women, the men were also abnormal in this respect, in that a higher proportion of hypopituitary than control men had total and LDL cholesterol above recommended values (> or = 6.2 and > or = 4.1 mmol/L, respectively). In the postprandial period (0730-2030 h), the areas under the curve (AUC) for circulating triglyceride and total cholesterol were significantly higher in hypopituitary than control women (P = 0.0089 and P = 0.0016, respectively). The AUC for triglyceride and total cholesterol over 24 h were also significantly increased (P = 0.009 and P = 0.0004, respectively). No significant differences were observed for postprandial and 24-h AUC for triglyceride and total cholesterol concentrations in men. We conclude that hypopituitarism with conventional replacement therapy is associated with unfavorable fasting and postprandial lipid and lipoprotein concentrations, particularly in women. The changes may contribute to the observed increased vascular morbidity and mortality.

Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women.

We tested the hypothesis that postmenopausal women on a soy-supplemented diet show estrogenic responses. Ninety-seven postmenopausal women were randomized to either a group that was provided with soy foods for 4 weeks or a control group that was instructed to eat as usual. Changes in urinary isoflavone concentrations served as a measure of compliance and phytoestrogen dose. Changes in serum FSH, LH, sex hormone binding globulin, and vaginal cytology were measured to assess estrogenic response. The percentage of vaginal superficial cells (indicative of estrogenicity) increased for 19% of those eating the diet compared with 8% of controls (P = 0.06 when tested by ordinal logistic regression). FSH and LH did not decrease significantly with dietary supplementation as hypothesized, nor did sex hormone binding globulin increase. Little change occurred in endogenous estradiol concentration or body weight during the diet. Women with large increases in urinary isoflavone concentrations were not more likely to show estrogenic responses than were women with more modest increases. On the basis of published estimates of phytoestrogen potency, a 4-week, soy-supplemented diet was expected to have estrogenic effects on the liver and pituitary in postmenopausal women, but estrogenic effects were not seen. At most, there was a small estrogenic effect on vaginal cytology.

Phytochemical mimicry of reproductive hormones and modulation of herbivore fertility by phytoestrogens.

Plants have physical and chemical mechanisms for defense from attack by animals. Phytochemical defenses that protect plants from attack by insects include antifeedants, insecticides, and insect growth regulators. Phytochemical options exist by which plants can modulate the fertility of the other major group of plant predators, vertebrate herbivores, and thereby reduce cumulative attacks by those herbivores. The success of such a defense depends upon phytochemical mimicry of vertebrate reproductive hormones. Phytoestrogens do mimic reproductive hormones and are proposed to be defensive substances produced by plants to modulate the fertility of herbivores.

An approach to the development of quantitative models to assess the effects of exposure to environmentally relevant levels of endocrine disruptors on homeostasis in adults.

The workshop "Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels" was held to provide a forum for discussions and recommendations of methods and data needed to improve risk assessments of endocrine disruptors. This article was produced by a working group charged with determining the basic mechanistic information that should be considered when designing models to quantitatively assess potential risks of environmental endocrine disruptors in adults. To reach this goal, we initially identified a set of potential organ system toxicities in males and females on the basis of known and/or suspected effects of endocrine disruptors on estrogen, androgen, and thyroid hormone systems. We used this integrated, systems-level approach because endocrine disruptors have the potential to exert toxicities at many levels and by many molecular mechanisms. Because a detailed analysis of all these untoward effects was beyond the scope of this workshop, we selected the specific end point of testicular function for a more detailed analysis. The goal was to identify the information required to develop a quantitative model(s) of the effects of endocrine disruptors on this system while focusing on spermatogenesis, sperm characteristics, and testicular steroidogenesis as specific markers. Testicular function was selected because it is a prototypical integrated end point that can be affected adversely by individual endocrine disruptors or chemical mixtures acting at one specific site or at multiple sites. Our specific objective was to gather the information needed to develop models in the adult organism containing functional homeostatic mechanisms, and for this reason we did not consider possible developmental toxicities. Homeostatic mechanisms have the potential to ameliorate or lessen the effects of endocrine disruptors, but these pathways are also potential target sites for the actions of these chemicals.

Workshop to identify critical windows of exposure for children's health: reproductive health in children and adolescents work group summary.

This work group report addresses the central question: What are the critical windows during development (preconception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health? The reproductive system develops in stages, with sex-specific organogenesis occurring prenatally and further maturational events occurring in the perinatal period and at puberty. Complex endocrine signals as well as other regulatory factors (genetics, growth factors) are involved at all stages. Evidence from animal models and human studies indicates that many specific events can be perturbed by a variety of toxicants, with endocrine-mediated mechanisms being the more widely studied. Prioritized research needs include basic studies on the cellular-molecular and endocrine regulation of sexual differentiation and development; increased efforts regarding potential adverse effects on development in females, including breast development; expanded animal studies on different classes of chemicals, comparing responses during development (prenatal and postnatal) with responses in adults; and, more extensive explorations regarding the reproductive biology and toxicology of puberty in humans.

A double-blind randomized study on the effects of red clover isoflavones on the endometrium.

OBJECTIVE: To assess the effects of a red clover-derived isoflavone extract on the Ki-67 proliferative marker of endometrial biopsies in 45-to 50-year-old perimenopausal women. We hypothesized that we would be able to detect a decrease in the Ki-67 proliferative index during the late follicular phase after a 3-month course of approximately 50 mg red clover isoflavones. Isoflavones have been found to have some antiestrogenic effects, and an antiproliferative effect during the perimenopausal period may be especially useful owing to the excessive endometrial proliferation often characteristic of this period. DESIGN: In a double-blind, randomized, controlled study, 30 women between the ages of 45 and 50 years consented to an endometrial biopsy before and after a 3-month course of either placebo or active isoflavone extract. The biopsies were timed as close as possible to days 7-11 of the menstrual cycle, and simultaneous measurements of transvaginal endometrial thickness, uterine artery Doppler, hormone profiles, lipids, and bone markers were performed. RESULTS: Of 30 women, 2 did not return for a second biopsy, and a third had an unsuccessful second biopsy. Four subjects were excluded from the Intention to Treat analysis because they did not have a menstrual bleed within the time frame of the study (3 subjects) or were tested on day 13 instead of between days 7 and 11 of the cycle (1 subject). There was no change in the Ki-67 proliferation index after treatment in either group. Eight subjects in the placebo group and eight in the P-07 group had proliferative endometrial biopsies that were synchronized with estradiol levels at baseline and post-treatment, and analysis of these subjects revealed no detectable change in the relationship between estradiol levels and Ki-67 with treatment in either group. There was no change in fasting lipids, bone markers, uterine Doppler resistance, or pulsatility index. CONCLUSION: In this small pilot study, we did not find, using immunohistochemical quantification of the Ki-67 antigen, that red clover isoflavones had an antiproliferative effect in the endometrium. Small sample size, examination of a relatively short interval in the menstrual cycle, and isoflavone formulation may have contributed to our lack of findings; however, we believe that the issue of isoflavones and their possible antiproliferative effect is deserving of further study. A simpler physiological model with less hormonal variability, such as healthy, recently menopausal women on predetermined doses of estrogen, may prove to be more informative.

hCG, progesterone, alpha-fetoprotein, and estradiol in the identification of ectopic pregnancy.

OBJECTIVE: To enhance the laboratory diagnosis of ectopic pregnancy by determining levels of hCG, progesterone, estradiol (E2), and alpha-fetoprotein (AFP). METHODS: Serum samples and medical records were retrospectively analyzed from 100 gynecologic patients for whom quantitative hCG determination had been ordered. Clinical data and levels of hCG, progesterone, E2, and AFP were examined by univariate and multivariate logistic analyses. RESULTS: Progesterone, hCG, and E2 were highest in viable pregnancies, whereas AFP tended to be higher in ectopic pregnancies. A single progesterone value could differentiate between ectopic and viable pregnancy in more than 80% of patients. The combination of all four biochemical markers predicted ectopic pregnancy with 98.5% specificity and 94.5% accuracy. Clinical diagnosis was less than 75% accurate. CONCLUSION: A combination of biochemical markers including hCG, progesterone, E2, and AFP can be superior to a single progesterone level or clinical evaluation in the diagnosis of ectopic pregnancy.

Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women.

Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy.

Serum progesterone for the exclusion of early pregnancy in women at risk for recurrent gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the utility of the serum progesterone level for discriminating pregnancy from gestational trophoblastic neoplasia. METHODS: Serum progesterone levels were measured in 61 women with histories of trophoblastic disease who developed a re-elevation in hCG during surveillance and underwent a work-up to differentiate pregnancy from gestational trophoblastic neoplasia. Progesterone levels were analyzed in the context of diagnostic outcome (pregnancy versus gestational trophoblastic neoplasia) to identify optimal threshold levels of progesterone to be used for classifying outcome. RESULTS: Of the 61 women, 37 proved to be pregnant and 24 had gestational trophoblastic neoplasia. Progesterone less than 2.5 ng/mL was predictive of trophoblastic malignancy, with a sensitivity of 83% (20 of 24 subjects were classified correctly as having gestational trophoblastic neoplasia) and a specificity of 95% (35 of 37 patients with progesterone levels at or above 2.5 ng/mL were correctly classified as pregnant). Progesterone of at least 10 ng/mL was associated with viable pregnancy in 97% of the cases. Furthermore, the progesterone level predicted outcome regardless of the serum hCG value. CONCLUSION: The serum progesterone level is useful for discriminating early pregnancy from gestational trophoblastic neoplasia.

Follicle-stimulating hormone concentrations in relation to active and passive smoking.

OBJECTIVE: To determine the association between various forms of tobacco exposure and ovarian status, as measured by FSH concentrations, in women 38-49 years old. METHODS: Two hundred ninety women between 38-49 years old, who had not had hysterectomy or oophorectomy, completed a self-administered questionnaire that included information on tobacco exposure and had serum FSH levels measured on days 2-4 of the menstrual cycle. Linear regression was used to assess the relation between FSH and tobacco exposure. RESULTS: Controlling for age and other factors, FSH concentrations were 66% higher among current smokers (geometric mean FSH 14.0 mIU/mL) and 39% higher among nonsmokers with passive smoke exposure (11.7 mIU/mL), compared to nonsmoking women without passive smoke exposure (8.4 mIU/mL). The estimated increase in FSH for each year of age was greater for current smokers than for nonsmokers (16 versus 6%, respectively). Ex-smokers did not have higher FSH concentrations, and there was no association between prenatal exposure to tobacco smoke and FSH. CONCLUSION: Both active and passive smoking are associated with elevated FSH concentrations in women 38-49 years old. The effect, limited to women with current exposure, is consistent with a shorter duration of the menopausal transition period.

Nausea and vomiting of pregnancy: role of human chorionic gonadotropin and 17-hydroxyprogesterone.

Although nausea and vomiting associated with early pregnancy are extremely common, the causal factors remain obscure. An endocrine etiology for this problem persists as a popular but unproved theory. The present study exn (hCG) and 17-hydroxyprogesterone (17-OHP) and the presence or severity of nausea and/or vomiting in women in the first 16 weeks of pregnancy. The occurrence and severity of nausea and/or vomiting in women with hydatidiform moles in relation to serum hCG levels were also investigated. Levels of hCG and 17-OHP in pregnant women grouped on the basis of severity of nausea and vomiting are compared to each other and to the levels found in normal pregnancies. No relationship could be established between the levels of hCG and 17-OHP and the incidence and severity of nausea and vomiting in either pregnant patients or in women with molar pregnancies.

The luteal phase in polycystic ovary syndrome during ovulation induction with human menopausal gonadotropin with and without leuprolide acetate.

Little data exist on the effects of adjunctive therapy with leuprolide acetate (LA) in the luteal phase of women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with human menopausal gonadotropin (hMG). Additionally, it is not known whether gonadal steroid concentrations in the luteal phase of induced cycles in PCOS are predictive of pregnancy. In this prospective, randomized study comparing cycles using hMG alone (n = 26) with cycles using hMG with LA (n = 33), no differences were noted between treatment groups in progesterone (P), estradiol (E2), and P:E2 ratios on luteal days 3, 6, and 9. When all treatment cycles were pooled, there were no differences in P, E2, or P:E2 ratios, comparing conception and nonconception cycles. We conclude that adjunctive therapy with LA in PCOS patients undergoing ovulation induction with hMG does not alter the luteal phase concentrations of P, E2, and P:E2. Furthermore, no correlation was found between the serum concentrations of these luteal phase steroids and cycle fecundity.