Changes In Metabolic Hormones Research Articles

RF10 | PMON215 Greater changes in metabolic hormones are associated with a smaller decrease in pulsatile LH secretion in response to short term moderate energy restriction in healthy, young women

Abstract Background Energy restriction may result in hypothalamic amenorrhea by inhibiting GnRH secretion and downstream pulsatile LH secretion. Energy restriction also leads to adaptive changes in metabolic hormones. We sought to determine whether metabolic changes in response to energy restriction predict or mitigate inhibition of GnRH secretion. Methods Nineteen healthy women, (mean age ± SD; 23.36 ± 2.08 yrs) with regular ovulatory cycles and no evidence of energy restriction or excessive exercise, underwent two 5-day dietary interventions with identical exercise in the early follicular phase of two menstrual cycles. A neutral energy availability (NEA; 45 kCal/kg*LBM/d) was followed by a deficient energy availability (DEA; 20 kCal/kg*LBM/d) diet. On day five of each intervention, body composition was analyzed (BodPod®), and blood was sampled between 0800 —1600 hours for LH, TSH and GH, every 10 min, cortisol every 30 min, T3, reverse T3 (rT3) and T4 every 60 min, free T3 (FT3), free T4 (FT4) and TBG at 0800 h and 1600 h. We correlated means of pulsatile LH pulse frequency (LHPF) with integrated metabolic hormone changes across the day in the subset of women with reduced or unchanged LHPF after DEA (n=10) using linear regression. Results In ∼50% of healthy young women, LHPF decreased or was unchanged in response to short-term moderate energy deprivation. BMI and bodyweight declined after DEA in both groups while % fat mass was unchanged. TSH, T3, leptin, insulin declined, and T4 increased from NEA to DEA while glucose, cortisol and GH were unchanged. In subjects with reduced/unchanged LHPF, % delta T3 correlated inversely with delta LHPF (r=-0.727, p=0.017). Similarly, non-fasting delta TSH correlated inversely with % delta LHPF (r=-0.643, p=0.045), and % delta AUC TSH (r=-0.642, p=0.045) correlated inversely with DEA LHPF. Percent delta insulin (r= -0.722, p=0.018) and % delta insulin AUC (r= – 0.688, p=0.028) correlated inversely with delta LHPF. Percent delta insulin-glucose ratio (r=-0.772, p=0.009) and % change in AUC insulin-glucose ratio (r=-0.759, p=0.011) also correlated inversely with delta LHPF. This inverse relationship was preserved when insulin was normalized for caloric intake (n-insulin) was correlated with % delta LHPF (r=-0.722, p=0.018) and % delta AUC n-insulin correlated with delta LHPF (r= -0.631 and p= 0.050). Delta AUC leptin (r=-0.684, p=0.029) and % delta AUC leptin (r=-0.670, p=0.034) also correlated inversely with delta LHPF. Mean cortisol at NEA correlated inversely with LHPF during DEA (r=-0.816, p=0.007), implying that higher baseline cortisol levels may predict a greater relative fall in LHPF. Cortisol AUC in DEA also correlated inversely with LHPF in DEA (r=-0.722, p=0.028). Conclusion Our data suggest that greater changes in metabolic hormones may protect against the inhibitory effect of moderate energy deprivation on GnRH secretion in healthy young women with normal reproductive function. Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Using participant ratings to construct food image paradigms for use in the Australian population – A pilot study

In human research, images of food are often used as cues in place of real foods. To elicit anticipatory responses in targeted populations (e.g. prompting changes in metabolic hormones, invoking food cravings), cultural differences and population norms with regard to food preferences need to be considered. This pilot study aimed to construct two image paradigms (healthy vs. hyperpalatable foods) for experimental use within the Australian population. A dataset of 200 images (from the licenced database Food-pics and internet sources), representative of healthy and hyperpalatable foods commonly consumed in Australia, was compiled by research dietitians. Ten male and female adults volunteered to view the images. Participants categorised each image as either healthy food or ‘junk food’ (i.e. hyperpalatable food), and rated each image according to three criteria: 1) familiarity of the food displayed; 2) recognisability of the food; and 3) appetisingness of the food. Overall, agreement with a priori categories was high for both healthy and hyperpalatable food images, 87.3% and 87.7% respectively. The food images with the lowest overall ratings (score <7 out of possible 9) were removed from the dataset and the final paradigms each contain 75 images. The healthy food paradigm contains foods from the five core food groups (fruit, vegetables, grains and cereals, meat and meat alternatives, dairy foods), and the hyperpalatable food paradigm contains non-core foods (sweet and savoury discretionary choice foods). The paradigms represent a broad range of commonly consumed foods that will be relevant for prospective projects utilising food cues in Australian adults.

Response.

Dear Editor-in-Chief, We believe that Loucks (1) has inaccurately represented our randomized controlled trial (RCT) designed to test the effects of 3 months of controlled exercise and diet at varying degrees of energy deficit on the induction of menstrual disturbances (MD) (2). Like Bullen et al. (3), we studied 35 previously untrained, eumenorrheic women who were screened to rule out existing organic, endocrine, and psychological causes of MD. Inclusion criteria included two screening cycles and one baseline eumenorrheic cycle with no MD as confirmed with serum (progesterone) and urinary (luteinizing hormone, estrogen, progesterone) measures. Our design allowed for a dose–response analysis with a control and three non-overlapping energy deficit groups. We demonstrated a dose–response relationship between the percent energy deficit and the incidence of MD (2). We confirmed this dose–response relationship in a follow-up analysis (4) where energy balance data were reanalyzed as “energy availability” in a manner similar to Loucks (5). We reported overall significant declines in T3 and IGF-1 with energy deficiency and weight loss relative to our weight-stable exercising control group (2). Dose–response–related changes in metabolic hormones, but not body weight, were demonstrated by Loucks’ 5-d studies, but notably all participants were not exposed to all treatments (semi-cross over design), and the data were analyzed using single-sided, one sample t-tests, providing more power in a single direction (5). As such, the assertion that our 3-month RCT should produce similar dose–response relationships in endocrine biomarkers between our deficit groups should be considered in light of several factors: 1) our RCT was not powered to detect differences among deficit groups in biomarkers or urinary E2, it was powered to detect MD as per our hypothesis of a dose–response relationship between MD and energy deficiency; 2) sources of variability affecting endocrine biomarkers include exercise training effects, the different combinations of diet and exercise among groups to achieve the prescribed energy deficit, individual variability in compensatory reductions in weight, body fat, and RMR (6); and 3) subject compliance to the fed diet outside the two supervised daily meals. These factors are more easily accounted for over 5 d as in Loucks et al. (5) than over 3 months. We reject Loucks’ suggestion that our findings reflect age-related menstrual instability. Any predisposition to MD due to nonintervention-related causes was spread evenly among groups given our RCT design. The stability of our subjects’ three preintervention cycle lengths is demonstrated by a within-person standard deviation of 1.2 d. Our intervention induced significantly more MD as energy deficiency increased, that is, 35% of cycles in up to 88% of women, whereas our exercising control group experienced MD in 16% of cycles in up to 13% of the subjects. In summary, we have demonstrated dose–response relations between energy deficiency and MD in two different articles from the same RCT (2,4). We have not observed a threshold effect of energy availability in these analyses, and we do not support the assertion that a critical threshold of energy availability is associated with MD in exercising women. Nancy I. Williams Mary Jane De Souza Department of Kinesiology Women’s Health and Exercise Laboratory Penn State University University Park, PA

Changes in Metabolic Hormones and Their Associations With Cancer-Related Fatigue in Cancer Survivors

Changes in Metabolic Hormones and Their Associations With Cancer-Related Fatigue in Cancer Survivors

Changes in metabolic hormones after bariatric surgery and their predictive impact on weight loss.

Although various metabolic hormones have been implicated in bariatric-related weight loss, their use as predictors of weight loss is unknown. Our study evaluates changes in metabolic hormones after bariatric surgery, and their role as predictors of weight loss. This nonrandomized study included 51 patients, 21 underwent laporascopic adjustable gastric banding (LAGB), 15 laparoscopic sleeve gastrectomy (LSG) and 15 Roux-en Y gastric bypass (RYGB). Serum ghrelin, leptin, insulin, growth hormone, HOMA-IR and HOMA-β was recorded at baseline and 1, 3, 6 and 12 months, and correlated with weight loss. Successful weight loss was defined as excess weight loss >50% at 12 months for all groups. Weight loss pattern was similar in all groups. Ghrelin increased only in the LAGB group (P = 0·016). However, baseline ghrelin concentrations >664·6 pg/mL in the LSG group predicted successful weight loss with 81·8% sensitivity and 100·0% specificity, and ghrelin >969·8 pg/mL in the 1st postoperative month predicted success with 83·3% sensitivity and 83·3% specificity in the LAGB group. Insulin and HOMA-IR decreased significantly in the LSG and RYGB group, HOMA-β increased in the LAGB and LSG group. Serum leptin decreased and GH increased in all groups (P < 0·001 for all changes). Changes in insulin, leptin and growth hormone were not predictors, but a consequence of weight loss. LSG is the most effective procedure for improvement of beta-cell function. High baseline ghrelin in the LSG group and an adequate 1st month increase in the LAGB group are associated with greater weight loss. Validation studies are required to confirm the role of ghrelin in predicting weight loss after bariatric surgery, but also in selecting candidates for specific bariatric procedures.

Changes in Metabolic Hormones in Malaysian Young Adults following Helicobacter pylori Eradication.

BackgroundMore than half of the world’s adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study.MethodsWe enrolled 29 H. pylori-positive young adult (18–30 year-old) volunteer subjects to evaluate the effect of H. pylori eradication on meal-associated changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes in body mass index and anthropometric measurements were recorded, pre- and post-eradication therapy.ResultsPre-prandial active amylin, total peptide YY (PYY) and pancreatic polypeptide (PP) levels were significantly elevated 12 months post-eradication compared with baseline (n = 18; Wilcoxon's signed rank test, p<0.05). Four of the post-prandial gut metabolic hormones levels (GLP-1, total PYY, active amylin, PP) were significantly higher 12 months post-eradication compared to baseline (n = 18; p<0.05). Following H. pylori eradication, the BMI and anthropometric values did not significantly change.ConclusionsOur study indicates that H. pylori eradication was associated with long-term disturbance in three hormones (active amylin, PP and total PYY) both pre- and post-prandially and one hormone (GLP-1) post-prandially. Longer post-eradication monitoring is needed to investigate the long-term impact of the observed hormonal changes on metabolic homeostasis.

Interrelationship between feeding level and the metabolic hormones leptin, ghrelin and obestatin in control of chicken egg laying and release of ovarian hormones

The aim of the present experiment is to examine the role of nutritional status, metabolic hormones and their interrelationships in the control of chicken ovarian ovulatory and secretory activity. For this purpose, we identified the effect of food restriction, administration of leptin, ghrelin 1-18, obestatin and combinations of food restriction with these hormones for 3days on chicken ovulation (egg laying) rate and ovarian hormone release. The release of progesterone (P), testosterone (T), estradiol (E) and arginine-vasotocin (AVT) by isolated and cultured ovarian fragments was determined by EIA. It was observed that food restriction significantly reduced the egg-laying rate, T, E and AVT release and promoted P output by ovarian fragments. Leptin, administrated to ad libitum–fed chickens, did not change these parameters besides promoting E release. Nevertheless, administration of leptin was able to prevent the effect of food restriction on ovulation, T and E (but not P or AVT) release. Ghrelin 1-18 administration to ad libitum–fed birds did not affect the measured parameters besides a reduction in P release. Ghrelin 1-18 administration prevented the food restriction–induced decrease in ovarian T, E and AVT, but it did not change P output or egg laying. Obestatin administrated to control chicken promoted their ovarian P, E and inhibited ovarian AVT release but did not affect egg laying. It was able to promote the effect of food restriction on P, T and AVT, but not E release or egg laying. Our results (1) confirm an inhibitory effect of food restriction on chicken ovulation rate; (2) shows that food restriction–induced reduction in egg laying is associated with a decrease in ovarian T, E and AVT and an increase in ovarian P release; (3) confirm the involvement of metabolic hormones leptin, ghrelin and obestatin in the control of chicken ovarian hormones output; and (4) the ability of metabolic hormones to mimic/antagonize or prevent/promote the effects of food restriction on both egg laying and ovarian hormones demonstrates that nutritional status can influence ovarian ovulatory and endocrine functions via changes in metabolic hormones.

Acute and chronic systemic CB1 cannabinoid receptor blockade improves blood pressure regulation and metabolic profile in hypertensive (mRen2)27 rats.

We investigated acute and chronic effects of CB1 cannabinoid receptor blockade in renin‐angiotensin system‐dependent hypertension using rimonabant (SR141716A), an orally active antagonist with central and peripheral actions. In transgenic (mRen2)27 rats, a model of angiotensin II‐dependent hypertension with increased body mass and insulin resistance, acute systemic blockade of CB1 receptors significantly reduced blood pressure within 90 min but had no effect in Sprague‐Dawley rats. No changes in metabolic hormones occurred with the acute treatment. During chronic CB1 receptor blockade, (mRen2)27 rats received daily oral administration of SR141716A (10 mg/kg/day) for 28 days. Systolic blood pressure was significantly reduced within 24 h, and at Day 21 of treatment values were 173 mmHg in vehicle versus 149 mmHg in drug‐treated rats (P < 0.01). This accompanied lower cumulative weight gain (22 vs. 42 g vehicle; P < 0.001), fat mass (2.0 vs. 2.9% of body weight; P < 0.05), and serum leptin (2.8 vs. 6.0 ng/mL; P < 0.05) and insulin (1.0 vs. 1.9 ng/mL; P < 0.01), following an initial transient decrease in food consumption. Conscious hemodynamic recordings indicate twofold increases occurred in spontaneous baroreflex sensitivity (P < 0.05) and heart rate variability (P < 0.01), measures of cardiac vagal tone. The beneficial actions of CB1 receptor blockade in (mRen2)27 rats support the interpretation that an upregulated endocannabinoid system contributes to hypertension and impaired autonomic function in this angiotensin II‐dependent model. We conclude that systemic CB1 receptor blockade may be an effective therapy for angiotensin II‐dependent hypertension and associated metabolic syndrome.

Obesity related alterations in plasma cytokines and metabolic hormones in chimpanzees.

Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1β and anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γ by PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.

Alterations in the equine oocyte and follicle associated with obesity and metabolic syndrome

Obesity is associated with disrupted reproductive cycles in mares, but the association between obesity and fertility has received minimal attention. In our first study, we hypothesized that mares with equine metabolic syndrome (EMS) have altered follicular environment compared to normal counterparts. Light-horse mares (11-27 yr) were classified as normal (CON; n1⁄412) or insulin resistant (EMS, n1⁄48) based on the reciprocal of the square root of insulin (RISQI) and modified insulin-to-glucose ratio (MIRG), with EMS having RISQI 5.50. Follicular fluid (FF), granulosa cells (GC), and oocytes were aspirated from dominant follicles 22-24 h after deslorelin and hCG administration. Blood was collected following an overnight fast for insulin (INS), leptin (LEP), adiponectin (ADIPO) and inflammatory cytokines. Expression for 32 genes, related to metabolism and follicle maturation, were assessed in GC. Concentrations of INS, LEP, ADIPO and cytokines were highly correlated in serum and FF (P<0.001). Insulin was lower in serum and FF of CON compared to EMS (P<0.001) while LEP and interleukin-1b tended to be lower in FF of CON (P1⁄40.07 and P1⁄40.10; respectively). Control mares had lower tumor necrosis factor-a in FF than EMS (P<0.05). Adiponectin was higher in serum and FF in CON vs. EMS (P<0.05). Gene expression for epiregulin was elevated (P<0.05) while tissue inhibitor of matrix metalloproteinase-2 tended to be lower (P1⁄40.09) in GC from CON vs. EMS. In a second study, we tested the hypotheses: 1) follicular fluid reflects systemic changes in metabolic hormones and metabolites, and 2) oocytes from obese mares have altered lipid content compared to mares

Increased food intake and changes in metabolic hormones in response to chronic sleep restriction alternated with short periods of sleep allowance

Rodent models for sleep restriction have good face validity when examining food intake and related regulatory metabolic hormones. However, in contrast to epidemiological studies in which sleep restriction is associated with body weight gain, sleep-restricted rats show a decrease in body weight. This difference with the human situation might be caused by the alternation between periods of sleep restriction and sleep allowance that often occur in real life. Therefore, we assessed the metabolic consequences of a chronic sleep restriction protocol that modeled working weeks with restricted sleep time alternated by weekends with sleep allowance. We hypothesized that this protocol could lead to body weight gain. Male Wistar rats were divided into three groups: sleep restriction (SR), forced activity control (FA), and home cage control (HC). SR rats were subjected to chronic sleep restriction by keeping them awake for 20 h per day in slowly rotating drums. To model the human condition, rats were subjected to a 4-wk protocol, with each week consisting of a 5-day period of sleep restriction followed by a 2-day period of sleep allowance. During the first experimental week, SR caused a clear attenuation of growth. In subsequent weeks, two important processes occurred: 1) a remarkable increase in food intake during SR days, 2) an increase in weight gain during the weekends of sleep allowance, even though food intake during those days was comparable to controls. In conclusion, our data revealed that the alternation between periods of sleep restriction and sleep allowance leads to complex changes in food intake and body weight, that prevent the weight loss normally seen in continuous sleep-restricted rats. Therefore, this "week-weekend" protocol may be a better model to study the metabolic consequences of restricted sleep.

Disruption of circadian clocks has ramifications for metabolism, brain, and behavior

Circadian (daily) rhythms are present in almost all plants and animals. In mammals, a brain clock located in the hypothalamic suprachiasmatic nucleus maintains synchrony between environmental light/dark cycles and physiology and behavior. Over the past 100 y, especially with the advent of electric lighting, modern society has resulted in a round-the-clock lifestyle, in which natural connections between rest/activity cycles and environmental light/dark cycles have been degraded or even broken. Instances in which rapid changes to sleep patterns are necessary, such as transmeridian air travel, demonstrate negative effects of acute circadian disruption on physiology and behavior. However, the ramifications of chronic disruption of the circadian clock for mental and physical health are not yet fully understood. By housing mice in 20-h light/dark cycles, incongruous with their endogenous ∼24-h circadian period, we were able to model the effects of chronic circadian disruption noninvasively. Housing in these conditions results in accelerated weight gain and obesity, as well as changes in metabolic hormones. In the brain, circadian-disrupted mice exhibit a loss of dendritic length and decreased complexity of neurons in the prelimbic prefrontal cortex, a brain region important in executive function and emotional control. Disrupted animals show decreases in cognitive flexibility and changes in emotionality consistent with the changes seen in neural architecture. How our findings translate to humans living and working in chronic circadian disruption is unknown, but we believe that this model can provide a foundation to understand how environmental disruption of circadian rhythms impacts the brain, behavior, and physiology.

Blood Metabolites During Basketball Competitions

This study examined basketball game blood hormonal and metabolite responses in 38 (8 guards, 18 forwards, and 12 centers) male national elite-junior players (age, 18.2 +/- 0.5 years; height, 1.89 +/- 0.1 m; body mass, 80.3 +/- 6.7 kg; body fat, 8.2 +/- 5.6%; maximum oxygen uptake Vo2max], 52.8 +/- 2.4 mlxkgxmin). At the moment of the investigation, players had 8 +/- 1.6 years of competitive experience. Blood samples were collected at the beginning, at halftime, and at fulltime of 6 junior competitive games (Tunisian under 19 basketball championship). Game intensity was assessed monitoring heart rates (HR). During the game, players attained 93 +/- 2% of maximal HR. Triglycerides (TG) and free fatty acids (FFA) concentrations significantly increased during the game, most markedly so in the second half. Postgame TG and FFA concentrations were significantly (p < 0.05 and p < 0.001, respectively) lower for guards (1.48 +/- 0.22 and 0.88 +/- 0.14 mmolxL, respectively) than for centers (1.88 +/- 0.30 and 1.08 +/- 0.09 mmolxL, respectively). Plasma glucose significantly increased at halftime (from 4.05 +/- 1.27 to 5.98 +/- 0.88 mmolxL; p < 0.001) but decreased in the second half. Serum insulin (INS) progressively decreased for all players during the game, whereas serum cortisol increased at the end of the first half (from 333 +/- 129 to 487 +/- 209 nmolxL; p < 0.001) to remain increased throughout the second half.Basketball game demands seem to induce significant metabolic-hormonal changes on players. Higher values of HR and glycemia were observed in the first half, but a more important increase of lipolytic variables was recorded in the second half. Changes in metabolic markers are role-dependent.

Endocrine profiles of periparturient mares and their foals1

The aim of this study was to characterize concentrations of leptin, IGF-I, and thyroid stimulating hormone (TSH) in the blood serum of mares pre-and postpartum, in the milk serum of mares postpartum, and in the blood serum of their foals. Nine pregnant Quarter Horse mares and their offspring were used in this study. Once weekly between 1000 and 1200 h for 2 wk before their predicted parturition date, mares were weighed, assigned a BCS, and blood was sampled via jugular venipuncture. Within 2 h of parturition and before the foals nursed (d 0), blood samples were obtained from the mares and foals, and a milk sample was collected from the mares. Blood from the foals and blood and milk from the mares were collected again at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 12, 19, 26, 33, and 61 d postpartum. Mares and foals also were weighed and assigned a BCS on d 0, 5, 12, 19, 26, 33, and 61. Additionally, on d 5, 33, and 61, ultrasound images of fat depth and area of the LM immediately cranial to and parallel with the last rib on the left side of the foals were measured to characterize changes in fat depth and LM area over time. There were no changes in mare blood concentrations TSH (P = 0.15), nor were there any changes in foal blood concentrations of leptin (P = 0.54) or TSH (P = 0.10) during the trial period. Mare blood concentrations of IGF-I tended to change over time (P = 0.07), whereas leptin changed over time (P < 0.001), initially decreasing and then remaining relatively stable after d 5. Foal blood concentrations of IGF-I increased initially, peaked at d 19, and stabilized thereafter (P < 0.001). Milk concentrations of leptin and TSH were greatest on d 0 and decreased over time (P < 0.007), reaching nadir concentrations at d 61. Milk concentrations of IGF-I also changed over time (P = 0.02), being greatest on d 0 and undetectable by d 12. There was no difference in BCS (P = 0.94) in mares over time, but there was a difference between pre- and postpartum BW (P < 0.001) due to foaling. However, no differences were detected in pre- (P = 0.70) or postpartum BW (P = 0.76) of mares over time. Mean ultrasonic fat depth and LM area increased (P < 0.04) as the foals aged, as did BCS and BW (P < 0.001). Recognizing changes in metabolic hormones surrounding the time of parturition in the mare and foal provides a basis for further determination of the role, if any, these hormones play in the milk, as well as in the neonate.

Examination of the direct effects of metabolic factors on somatotrope function in a non-human primate model, Papio anubis

In humans, circulating GH levels are increased in catabolic states and suppressed in obesity. In both extremes, normalization of the metabolic environment normalizes GH release, leading to the conclusion that changes in metabolic hormones and/or metabolites promote changes in GH synthesis and release. Metabolic regulation of GH secretion can be mediated centrally by modulation of hypothalamic GHRH and somatostatin input to the pituitary and/or by direct regulation of pituitary somatotrope function. Although data are available showing glucocorticoids, free fatty acids (FFA), IGF-I, and insulin have direct effects on rat somatotrope function, little information is available regarding the direct pituitary effects of these metabolic factors in primates. Therefore, this study examined the effects of glucocorticoids (dexamethasone (0.1-100 nM) and hydrocortisone (10 nM)), FFA (oleic and linoleic acid, 100 and 400 microM each), IGF-I (0.5-50 nM), and insulin (0.5-50 nM) on GH release and GH, GHRH-receptor (GHRH-R) and ghrelin-receptor (GHS-R) mRNA levels, in primary pituitary cell cultures of baboons (Papio anubis) after 24 h treatment. A commercial ELISA kit was used to determine the amount of GH released into the media, while quantitative real-time reverse transcription-PCR was used to determine mRNA levels. To design species-specific primers for baboon GH, GHRH-R, GHS-R, insulin receptor (INSR), IGF-I receptor (IGF-IR), pituitary-specific transcription factor-1 (Pit-1), and cyclophilin A (used as a housekeeping gene) cDNA, sequence data for each baboon transcript were obtained and this data were submitted to Genbank. Glucocorticoids, FFA, insulin and IGF-I treatment did not significantly alter the expression of Pit-1, a transcription factor essential for normal somatotrope development and function. However, as previously reported in the rat, glucocorticoids increased, while FFA, IGF-I and insulin decreased GH release in baboon pituitary cell cultures, where changes in GH release were reflected by comparable changes in GH mRNA levels. In addition, glucocorticoids increased, while FFA, IGF-I and insulin decreased the expression of the GH stimulatory receptors, GHRH-R and GHS-R, without significantly altering cyclophilin A mRNA levels. A role of insulin/INSR pathway, independent of IGF-I, in regulating pituitary function is supported by the fact that (1) IGF-I and insulin significantly suppressed somatotrope function at doses (0.5 and 5 nM respectively) not anticipated to activate their respective receptors, and (2) the baboon pituitary expresses INSR mRNA at levels comparable to or greater than that of tissues commonly considered as insulin sensitive (i.e. liver, skeletal muscle, and fat). Taken together, these results demonstrate that metabolic factors can directly modulate primate somatotrope function through regulating GH synthesis and release, as well as mediating the expression of receptors important in central (GHRH) and systemic (ghrelin) regulation of GH secretion.

Abdominal obesity, insulin resistance, and colon carcinogenesis are increased in mutant mice lacking gastrin gene expression

The authors recently reported that gastrin gene knockout (GAS-KO) mice had an increased risk for colon carcinogenesis in response to azoxymethane (AOM) compared with their wild type (WT) littermates. In the current report, the authors discuss the predisposition of GAS-KO mice to develop obesity and metabolic hormonal changes that may contribute to their increased risk of colon carcinogenesis. The weight and deposition of fat was monitored in the mice over a 14 month period, using magnetic resonance imaging and nuclear magnetic resonance techniques. Changes in plasma concentrations of ghrelin, leptin, insulin, and glucose were assessed using radioimmunoassay analysis and enzyme-linked immunosorbent assays. Preneoplastic markers of colon carcinogenesis (aberrant crypt foci [ACFs]), in response to AOM, were measured in a subset of obese versus lean GAS-KO mice and were compared with the markers in WT mice. Increases in visceral adiposity were evident by age 2 months in GAS-KO mice, resulting in macroscopic obesity by age 7 months. Hyperinsulinemia and insulin:glucose ratios were increased significantly in GAS-KO mice as young as 1 month and preceded alterations in nonfasting leptin and ghrelin levels. The number of ACFs per mouse colon were increased significantly in the following order: obese GAS-KO mice > lean GAS-KO mice > WT mice. Fasting plasma insulin levels were 0.88 +/- 0.1 ng/mL, 1.45 +/- 0.3, and 2.76 +/- 0.9 ng/mL in the WT, GAS-KO lean, and GAS-KO obese mice, respectively. The current results suggest the novel possibility that loss of amidated gastrins may increase adipogenesis, hyperinsulinemia, and colon carcinogenesis in GAS-KO mice. The increase in colon carcinogenesis may be due in part to hyperinsulinemia, increased obesity, and other associated hormone changes that were measured in GAS-KO mice.

Influence of metabolic hormones and nutrition on ovarian follicle development in cattle: practical implications

Nutrition has long been known to have a profound influence on reproductive performance of female cattle, but the underlying mechanism remains poorly understood. Whilst early investigations focused on the modulation of nutrition on hypothalamic–pituitary axis, more recent studies have tested the hypothesis that metabolic hormones as nutritional signals exert a direct effect at the ovarian level. In cattle, treatment with recombinant bovine somatotrophin (rGH) significantly increases the population of small ovarian follicles. This is associated with increases in circulating concentrations of insulin and insulin-like growth factor-I (IGF-I). Subsequent studies, both in vitro and in vivo, have highlighted the importance of IGF-I and/or insulin acting in synergy with FSH and LH. More recently, we demonstrated that feeding heifers with 200% maintenance requirements for a short period significantly increases circulating insulin concentrations and population of small ovarian follicles. Based on these findings, our recent work has aimed at addressing some practical problems in cattle production. Firstly, we showed that both rGH pretreatment and increased dietary intake significantly enhance the response to standard superovulatory regimes. Secondly, we have demonstrated that feeding a diet to increase circulating insulin concentrations during the early lactation can advance the first ovulation postpartum and increase conception rate to the first service in dairy cows. In summary, nutrition influences ovarian follicle development in cattle possibly through changes in metabolic hormones. These interactions can be manipulated to improve reproductive performance.

Feed restriction in cyclic gilts: gonadotrophin-independent effects on follicular growth.

Our objective was to determine whether changes in metabolic hormones, induced by feed restriction, can alter follicle distribution in swine ovaries through effects independent of LH pulsatility. In a factorial arrangement, 24 gilts were fed a high or a low level of dietary energy (240 or 80% of maintenance requirements) and given an antagonist of GnRH or saline between days 3 and 12 of the oestrous cycle. Serial blood samples were collected on day 12 and ovaries on day 13. Antagonist treatment, that blocked LH pulsatility, decreased the number of follicles larger than 2 mm and increased the number of follicles smaller than 1 mm. The feed restriction did not alter gonadotrophin secretion, decreased the number of follicles smaller than 1 mm and increased the number of 1 - to 1.9-mm follicles. These findings indicate that feed restriction can alter the growth of small follicles independently of gonadotrophin levels.

Effects of post-ovulatory food deprivation on oviductal sperm concentration, embryo development and hormonal profiles in the pig.

Nutrition is one of the multiple factors that modulate reproduction in animals. The effect of 48 h food deprivation on reproductive and metabolic hormonal changes in relation to cleavage rates was studied. Insemination of 15 sows was performed 20-10 h prior to expected ovulation and ova were recovered at slaughter 65-91 h post ovulation. Blood samples were collected every second hour, beginning from the time of insemination until slaughter, for measurements of progesterone, cortisol, the prostaglandin F2alpha metabolite (15-keto-13,14-dihydro-PGF2alpha) and insulin levels. The embryos from the food-deprived sows (D-group) had fewer accessory spermatozoa in their zona pellucida (ZP) compared with the control sows (C-group). A lower cleavage rate of the embryos in the D-group compared with the C-group was detected. Plasma progesterone, cortisol and prostaglandin F2alpha metabolite levels were significantly higher in the D-group compared with the C-group. Food deprivation is associated with changes in reproductive and metabolic hormones that might lead to changes in the oviductal environment, culminating in a lower cleavage rate of the embryos and presence of fewer viable spermatozoa in the reservoir.

Effect of age at weaning (30 vs. 60 day) on intake, growth, serum hormone and metabolite profiles in young ewe and ram lambs

Twenty-four Polypay lambs (12 sets of twins; 12 ewe and 12 ram lambs) born within a 3-d period were randomly allotted at birth within sex group to be weaned at either 30 (EW) or 60 (LW) d of age. Six lambs (three ewe and three ram lambs)/treatment were intensively bled at 30, 37, 60, and 67 d of age. Feed intake was higher (P &lt; 0.05) in EW lambs following weaning and up through weaning of LW lambs. Throughout the study, BW were similar (P &gt; 0.10) between treatments; however, ram lambs were heavier (P &lt; 0.05) than ewe lambs beginning at 18 d of age. At 37 d of age, EW lambs had lower (P &lt; 0.05) insulin and IGF-I concentrations (P = 0.10), and greater (P &lt; 0.05) GHmn values than LW lambs. Ram lambs had greater (P &lt; 0.05) serum GHmn, GHbl and GHam values, and greater (P &lt; 0.05) serum insulin and IGF-I concentrations than ewe lambs at 30, 60, and 67 d of age. At 37 d of age, EW lambs had lower (P &lt; 0.05) insulin:GH ratios than LW lambs. At 37 d of age, PRLmn and PRLam values were lower (P &lt; 0.05) in EW lambs than LW Lambs, and rams had lower (P &lt; 0.05) PRLam values than ewe lambs. The results indicate that weaning at 30 d of age is associated with major changes in metabolic hormones 1 wk postweaning, whereas weaning at 60 d of age had no apparent effect on hormonal patterns postweaning. Differences between EW and LW lambs may reflect early postweaning feed intake, along with stage of rumen development at weaning. Key words: Lambs, growth, hormones, weaning, metabolites