Maternal serum leptin in the pregnant rat: fetal-placental implantation number and progesterone.

PURPOSE: This study was designed to determine whether there is a role of the placenta in the regulation of maternal serum leptin levels in the pregnant rat. METHODS: We have adjusted the number of fetal-placental implants on day 9 in the pregnant rat by aspirating fetal-placental units to adjust the number to 1-2, 4-5 per rat or >10 in controls. Serum levels of leptin and progesterone were determined by radioimmunoassay. A separate group of pregnant rats were ovariectomized and maintained with progesterone silastic capsules (10, 20 or 40 mm). RESULTS: In the pregnant rats with varied fetal-placental implant numbers, the maternal serum leptin were greatest in the group with the smallest number (1-2) of implants; intermediate in the midgroup (4-5 implants); and lowest in the group with a full complement of implantations (>10) (p < 0.001). Serum progesterone levels are lowest in the 1-2 implantation group. In the ovariectomized rats there was a stepwise decline in serum leptin (p < 0.05) as the dose of progesterone increased (p < 0.01). Both of these studies suggest that progesterone suppressed maternal serum leptin levels. CONCLUSIONS: Increasing placental mass is not associated with increasing maternal serum leptin levels in the pregnant rat; the contrary condition is observed with the least placental implants having the highest leptin levels. Progesterone seems to suppress serum leptin levels in several physiological models.

Perils of prolonged ovarian suppression and hypoestrogenism in the treatment of breast cancer: Is the risk of treatment worse than the risk of recurrence?

Premenopausal breast cancer is usually estrogen receptor positive, and hence, prolonged ovarian suppression by medical or surgical means to prevent recurrence has become standard of management to improve disease-free survival. Ten-year adjuvant tamoxifen therapy is associated with 3.5% fewer recurrences compared to five years. The SOFT trial demonstrated small but statistically significant incremental improvements in long-term disease-free survival by the addition of gonadotropin-releasing hormone analog treatment (triptorelin) to an aromatase inhibitor (exemestane). Profound hypoestrogenism in the premenopausal age group may not be well tolerated due to a host of bothersome side effects (primarily vasomotor symptoms, musculoskeletal complaints, genitourinary syndrome of menopause, and mood disorders). Prolonged hypoestrogenism in younger women is associated with premature development of cardiovascular disease, bone loss, cognitive decline, and all-cause mortality. This paper explores multi-system consequences of prolonged hypoestrogenism in premenopausal women derived from studies of women with and without breast cancer. Pretreatment counseling in estrogen receptor positive breast cancer should emphasize the benefit of prolonged estrogen suppression on breast cancer recurrence and established risks of lifelong hypoestrogenism on quality of life and all-cause mortality. Future genomic research may help identify the best candidates for extended ovarian suppression to avoid treating many women when only a minority benefit.

Understanding vitamin D metabolism in pregnancy: From physiology to pathophysiology and clinical outcomes.

This critical time frame of intrauterine life development is considered of major importance on the metabolic imprinting of overall health of the offspring, in later life. This requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Dysregulation of these tightly controlled biophenomena at a systemic and placental level, have been considered as a potential mechanism mediating pathogenesis of preeclampsia and spontaneous birth. In this context, vitamin D has been considered as a significant regulator of both innate and adaptive immunity by regulating cell proliferation, differentiation and apoptosis. Vitamin D metabolism during pregnancy manifests striking differences as compared to the non-pregnant state. Calcitriol is increasing >2-3 fold in the first weeks of pregnancy whereas maternal 25-hydroxyvitamin D crosses the placental barrier and represents the main pool of vitamin D in the fetus. Moreover, during pregnancy, vitamin D receptor and regulatory metabolic enzymes are expressed in the placenta and decidua, indicating a potential critical point in the immunomodulation at the maternal-fetal interface. Considering these effects, maternal hypovitaminosis D during pregnancy has been associated with pregnancy related disorders. This review focuses on the mechanistic basis of these adaptive changes, as a background for the development of pregnancy related disorders, with a discourse on the pathophysiology relating hypovitaminosis D and clinical outcomes.

Adipose tissue and reproductive health.

The understanding of adipose tissue role has evolved from that of a depot energy storage organ to a dynamic endocrine organ. While genetics, sexual phenotype and sex steroids can impact the mass and distribution of adipose tissue, there is a counter-influence of white adipocytes on reproduction. This primarily occurs via the secretion of adipokines, the most studied of which- leptin and adiponectin- are highlighted in this article. Leptin, the "satiety hormone" primarily acts on the hypothalamus via pro-opiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AgRP) neurons to translate acute changes in nutrition and energy expenditure, as well as chronic adipose accumulation into changes in appetite and potentially mediate insulin resistance via shared pathway and notably impacting reproductive health via influence on GnRH secreting neurons. Meanwhile, adiponectin is notable for its action in mediating insulin sensitivity, with receptors found at every level of the reproductive axis. Both have been examined in the context of physiologic and pathologic reproductive conditions. Leptin has been shown to influence puberty, pregnancy, hypothalamic amenorrhea, and lipodystrophy, and with a potential therapeutic role for both metabolic and reproductive health. Adiponectin mediates the relative state of insulin resistance in pregnancy, and has been implicated in conditions such as polycystic ovary syndrome and reproductive malignancies. There are numerous other adipokines, including resistin, visfatin, chemerin and retinol binding protein-4, which may also play roles in reproductive health and disease states. The continued examination of these and other adipokines in both normal reproduction and reproductive pathologies represents an important avenue for continued study. Here, we seek to provide a broad, yet comprehensive overview of many facets of these relationships and highlight areas of consideration for clinicians and future study.

Effects of partial vascular occlusion on irisin responses to loaded muscle contractions.

The purpose of the study was to determine the effects of partial vascular occlusion on irisin responses. Eight males completed trials of light (30% 1-repetition maximum (1RM)) resistance exercise (single biceps curls and calf presses) with partial vascular occlusion (LRO), moderate resistance (70% 1RM) with no occlusion (MR), and occlusion only (OO). Blood was collected before, after, and 15 min after exercise. Changes in circulating irisin were more affected during LRO than MR and OO trials.

Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise.

Increased plasma cell-free mitochondrial DNA (cf-mDNA), a damage-associated molecular pattern (DAMP) produced by cellular injury, contributes to neutrophil activation/inflammation in trauma patients and arises in cancer and autoimmunity. To further understand relationships between cf-mDNA released by tissue injury, inflammation, and health benefits of exercise, we examined cf-mDNA response to prolonged moderate aerobic exercise. Seven healthy moderately trained young men (age = 22.4 ± 1.2) completed a treadmill exercise trial for 90 min at 60% VO2 max and a resting control trial. Blood was sampled immediately prior to exercise (0 min = baseline), during (+18, +54 min), immediately after (+90 min), and after recovery (R40). Plasma was analyzed for cf-mDNA, IL-6, and lactate. A significant difference in cf-mDNA response was observed between exercise and control trials, with cf-mDNA levels reduced during exercise at +54 and +90 (with or without plasma volume shift correction). Declines in cf-mDNA were accompanied by increased lactate and followed by an increase in IL-6, suggesting a temporal association with muscle stress and inflammatory processes. Our novel finding of cf-mDNA decline with prolonged moderate treadmill exercise provides evidence for increased clearance from or reduced release of cf-mDNA into the blood with prolonged exercise. These studies contrast with previous investigations involving exhaustive short-term treadmill exercise, in which no change in cf-mDNA levels were reported, and contribute to our understanding of differences between exercise- and trauma-induced inflammation. We propose that transient declines in cf-mDNA may induce health benefits, by reducing systemic inflammation.

The Microbiota and Transgenomic Networks: Potential Implications for Maternal-Fetal Medicine.

The maternal microbiota has long been considered a potential cause for adverse perinatal outcomes. Gene expression regulators in prokaryotic and eukaryotic cells are influenced by changes in their microenvironments. We propose the novel idea that during in utero development, an adaptive and dynamic gene-regulatory cross talk might exist between the host genome and the maternal microbiota. Understanding these cross talks could increase the appreciation for the discovery of new diagnostics and therapeutics in maternal-fetal medicine.

Endocrine alterations from concentric vs. eccentric muscle actions: a brief review.

Resistance exercise has a positive effect on many tissues, including heart, bone, skeletal muscle, and nervous tissue. Eccentric muscle actions offer a unique and a potentially beneficial form of exercise for maintaining and improving health. During resistance exercise, the effects of gravity, and mechanical properties of the sarcomere and connective tissue in skeletal muscle allow a greater muscle load during an eccentric (lengthening) muscle contraction than a concentric (shortening) muscle contraction. Consequently, older patients, patients with muscle or limb movement limitations or injuries, as well as cancer patients may be able to benefit from isolated eccentric muscle actions. There are specific physiological responses to eccentric muscle contractions. This review will describe the effects of different eccentric muscle contraction protocols on endocrine responses that could have positive effects on different tissues and recommend direction for future research.

No effect of menstrual cycle phase on glucose and glucoregulatory endocrine responses to prolonged exercise.

INTRODUCTION: Prolonged exercise requires increased utilization of blood glucose and adjustment of glucoregulatory hormones. Estrogen can reduce hepatic gluconeogenesis which could affect insulin concentrations. Amylin is co-secreted with insulin and controls influx of glucose into the blood. PURPOSE: To determine the effect of menstrual cycle stage on glucose, leptin, and pancreatic hormone responses to prolonged (90 min) exercise. METHODS: Five healthy, eumenorrheic women (24.6 ± 5.1 years; 67.4 ± 1 kg) were monitored for 3 months to determine menstrual cycle length. Subjects completed a preliminary session to determine exercise workloads and, in a fasted condition, completed two randomized 90-min treadmill exercise trials at 60 % VO2max during the early follicular (EFX) and mid-luteal phase (MLX) of their menstrual cycle. Blood samples were analyzed for glucose, insulin, C-peptide, amylin, glucagon, leptin, and cortisol concentrations at rest (-30 and 0 min), during exercise (18, 36, 54, 72, and 90 min) and after 20 min of recovery. RESULTS: No changes in amylin, leptin, or cortisol occurred for EFX and MLX trials. A significant (p < 0.05) time effect occurred for glucose, insulin, and glucagon with reduced insulin across the exercise trial and increases in glucose and glucagon later in the trial, but there were no differences between the EFX and MLX trials. CONCLUSIONS: Menstrual cycle stage does not affect glucose, insulin, C-peptide, amylin, glucagon, cortisol, and leptin responses to prolonged exercise; however, the exercise reduces insulin and increases glucose and glucagon concentrations. This is the first study to determine acute effects of exercise on amylin and other glucoregulatory hormone responses in women.

Estrogen mediation of hormone responses to exercise.

The roles of estrogens extend from the regulation of reproduction to other functions involved in control of metabolism, fluid balance, as well as gastrointestinal, lung, and brain function, with a strong effect on other hormones that subsequently alter the physiology of multiple tissues. As such, alteration of endogenous estrogens across the menstrual cycle, or from oral contraception and estrogen replacement therapy, can affect these tissues. Due to the important effects that estrogens have on different tissues, there are many investigations concerning the effects of a human estrogenic environment on endocrine responses to exercise. The following review will describe the consequences of varying estrogen levels on pituitary, adrenal, gonadal, and endocrine function, followed by discussion of the outcomes of different estrogen levels on endocrine tissues in response to exercise, problems encountered for interpretation of findings, and recommended direction for future research.

Effects of prolonged exercise on agouti-related protein: a pilot study.

Agouti-related protein (AgRP), is a signaling peptide that affects feeding behavior, energy homeostasis, and has also been shown to stimulate the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine the effects of 90 min of treadmill exercise on circulating AgRP concentrations and the relationship of AgRP responses to cortisol. Seven young males completed a preliminary trial followed by counterbalanced experimental and control trials 4-5 weeks apart. The experimental trial began 2.5 h after consumption of a standard nutrient beverage and consisted of treadmill exercise at 60 % of previously determined VO(2max) for 90 min. Blood samples were collected before (-30 and 0 min), during (18, 36, 54, 72, and 90 min), and following exercise (20, 40, and 60 min). Blood samples were collected in a resting, control trial at the same time points as the experimental trial. Plasma lactate was significantly higher in the exercise than the control trial. Although AgRP increased from 18 min of exercise to peak at 90 min, these increases were not significantly different than values in the control trial. Cortisol responses during the exercise trial were significantly higher than the control trial. AgRP concentrations during early exercise were positively correlated with cortisol levels later in recovery. The obtained data suggest that AgRP concentrations during prolonged steady-state exercise are associated with subsequent cortisol increases, but further study is required to determine whether there is a causal effect.

Lipoprotein profiles in Mexican American and non-Hispanic white women with polycystic ovary syndrome.

OBJECTIVE: To compare lipid profiles between Mexican American and non-Hispanic white women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional analysis using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. SETTING: University gynecology service. PATIENT(S): Self-identified Mexican Americans (n = 71) and non-Hispanic whites (n = 120) with PCOS defined by the 2003 European Society of Human Reproduction and Embryology and American Society of Reproductive Medicine consensus. INTERVENTION(S): Serum drawn from fasting state followed by oral glucose tolerance test. MAIN OUTCOME MEASURE(S): Age, body mass index (BMI), androgens, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, fasting, and minimal model analyses of insulin sensitivity. RESULT(S): Mexican American women were more insulin resistant than non-Hispanic whites, but cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol levels were similar. BMI inversely correlated with HDL cholesterol and positively with triglycerides. Approximately half of both ethnic groups had at least one lipid level in the low (HDL) or high (cholesterol, triglycerides, and LDL cholesterol) range according to National Cholesterol Education Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults guidelines. CONCLUSION(S): Despite greater insulin resistance among Mexican Americans with PCOS, lipid levels were similar to those of age- and weight-matched non-Hispanic whites. Obesity adversely affected lipid levels-primarily HDL cholesterol and triglycerides-in both groups. The prevalence of dyslipidemia was approximately 50% in each ethnic group.

Stress reactivity to repeated low-level challenges: a pilot study.

The purpose of this study was to examine the effects of a mental challenge on cardiovascular and endocrine [epinephrine (EPI), norepinephrine (NE), and cortisol (CORT)] responses to subsequent low-intensity physical exertion. Twelve males (23.25±0.45 years) completed three sessions, including a graded exercise test on a cycle ergometer and two counter-balanced mental stress trials. In the mental challenge-control condition (MC), participants sat quietly for 20 min following a 20 min mental challenge whereas in the mental challenge-exercise condition (MEC) subjects cycled at 35% of maximal oxygen consumption (VO2max) following the mental challenge. Repeated-measures ANOVAs were used to assess state anxiety (SAI), cardiovascular variables, EPI, NE, and CORT levels across time between conditions. Participants reported significantly greater increases in SAI scores immediately after the mental challenge, which then decreased post-challenge in both conditions. Neither EPI or NE demonstrated an alteration in levels in either condition, but CORT significantly increased after the mental challenge in both conditions and then maintained a significantly greater level during the MEC compared to the MC condition from midexercise through 15 min of recovery. Area-under-the-curve calculations for CORT was significantly greater in the MEC compared to the MC. Results suggest that the initial mental challenge may have acted to enhance the overall adrenal response to the subsequent anticipation of and actual participation in the low-level physical challenge.

Serum magnesium concentrations and metabolic variables in polycystic ovary syndrome.

OBJECTIVE: Hypomagnesemia is associated with diabetes mellitus type 2 and other components of the metabolic syndrome in older patients. Whether serum magnesium concentrations correlate with insulin resistance, obesity, hypertension, dyslipidemia, or other components of metabolic syndrome in younger women with polycystic ovary syndrome (PCOS) is currently unknown. DESIGN: Cross-sectional analysis. SETTING: Academic medical center. POPULATION: 100 consecutive women with PCOS by the Rotterdam criteria and 20 age- and BMI-matched normal women. METHODS: Statistical analysis of the relationship between magnesium levels and a variety of physical, endocrine, and metabolic variables. The STROBE guidelines for a cross-sectional analysis were followed. MAIN OUTCOME MEASUREMENTS: Serum magnesium levels, insulin sensitivity indices, and glucose assessments. BMI, waist circumference, blood pressure, and lipids served as secondary endpoint measurements. RESULTS: No patient demonstrated hypomagnesemia. Magnesium levels did not differ between women with and those without insulin resistance, glucose intolerance, or hypertension. Magnesium levels were similar across PCOS phenotypes and WHO-defined BMI categories. Multiple regression analysis did not suggest that serum magnesium concentrations correlated with any physical, metabolic, or endocrine variable. CONCLUSIONS: Magnesium levels do not correspond with age, BMI, waist circumference, insulin sensitivity, glycemic levels, blood pressure, or lipid levels in reproductive-age women with PCOS. Magnesium concentrations are similar across PCOS phenotypes and indistinguishable from women without PCOS.

Amylin and selective glucoregulatory peptide alterations during prolonged exercise.

UNLABELLED: Amylin is a pancreatic ß-cell peptide that facilitates the regulation of blood glucose concentration by inhibiting release of glucagon and modulating gastric emptying. Prolonged exercise may alter amylin and aid in the maintenance of blood glucose concentration; however, no studies have investigated the effects of prolonged exercise on amylin. PURPOSE: This study aimed to determine the effects of 90 min of treadmill exercise on amylin and other glucoregulatory hormone responses in a postprandial state. METHODS: Eight young healthy males completed a preliminary trial for VO2max and body composition determination and subsequent experimental and control trials in a counterbalanced manner. The experimental trial subjects arrived at the laboratory at 8:00 a.m., 1 h after consumption of a standard nutrient beverage (Ensure Plus®). At 9:50 a.m., subjects initiated 90 min of treadmill exercise at 60% of VO2max. Blood samples were collected twice before exercise, every 18 min during exercise, and every 20 min during 1 h of recovery. A resting control trial was conducted in an identical manner without VO2 assessment. RESULTS: Plasma glucose and leptin concentrations remained stable across exercise, whereas lactate significantly increased to peak at 18 min of exercise then gradually declined. Amylin, insulin, and C-peptide values significantly declined over the trials, with no difference between exercise and control days. Glucagon area-under-the-curve concentrations were significantly greater during the exercise than the control trials. There was a significant time effect and trial effect for cortisol with a higher concentration during the experimental trial than during the control trial. CONCLUSIONS: In a postprandial state, prolonged exercise stimulates glucagon and cortisol increases that are associated with stable blood glucose and leptin concentrations; however, similar to postprandial state control condition, insulin, C-peptide, and amylin concentrations decline.

A simple, innovative surgical-instruction tool.

In the present report, we demonstrate the utility of a knitting needle as a device to improve the teaching of surgical principals and practice. Although we emphasize obstetric and gynecologic surgery, these techniques can easily be applied to other surgical specialties.

Endocrine factors associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome: do androgens play a role?

OBJECTIVE: To characterise the metabolic profile of women with polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD) and to determine whether circulating androgens differ in PCOS women with NAFLD compared to PCOS subjects without NAFLD. METHODS: Retrospective study of 21 women with PCOS, elevated liver enzymes and ultrasound evidence of hepatic steatosis matched with 32 PCOS women with normal liver enzymes. Extensive demographic, endocrine and metabolic data were compared. Pearson's correlation coefficients were calculated to assess for potential relationships between the free androgen index (FAI) and other dependent variables. RESULTS: PCOS subjects with NAFLD demonstrate greater insulin resistance but have similar circulating androgen levels. CONCLUSION: In this pilot study, insulin resistance was the most prominent feature characterising NAFLD complicating PCOS. Total testosterone, FAI, DHEAS and 17-hydroxyprogesterone levels were similar between patients with PCOS and without NAFLD.

Load rather than contraction type influences rate of perceived exertion and pain.

The purpose of the study was to determine whether muscle contraction type (concentric [CON] or eccentric [ECC]) or loading (relative or absolute) has a greater impact on the perceptual and metabolic responses to conventional resistance exercise. Additionally, overall effort, pain sensations, and specific pain descriptors were compared with physiological responses. Seven healthy men (mean +/- SE, 25.71 +/- 2.17 years) with resistance training experience completed 2 one-repetition maximum (1-RM) trials. Subsequently, 2 randomized, counterbalanced, experimental sessions were completed consisting of 4 sets of 10 repetitions for 6 exercises. These sessions were performed at 65% CON 1-RM for CON only contractions or 65% CON 1-RM + 20% for ECC contractions. Blood samples were taken pre, post, and 15 minutes postexercise. OMNI-RPE (OMNI-Res), CR-10 pain rating, McGill pain ratings, and heart rate (HR) were recorded after each set. A significant time effect occurred for OMNI-Res, pain, lactate, and HR (p < 0.05). No significant pattern emerged for the contraction type, except for higher HR and lactate immediately postexercise for the CON contractions. Physiological measures were not significantly related to perceptual measures. When considered with previous data, muscle loading rather than contraction type plays the primary role in perceptual alterations of effort sense and pain. Practical applications of the investigation are that strength and conditioning professionals may be able to load CON and ECC contractions in a relative fashion by increasing loads in the ECC portion by 20% above the CON load that would result in comparable perceptual experiences.