Plasma Growth Hormone Research Articles

Acute and chronic effects of cortisol on milk yield, the expression of key receptors, and apoptosis of mammary epithelial cells in Saanen goats

Cortisol (CORT) induces mammary development in late gestation and is fundamental to the differentiation of mammary epithelial cells and lactogenesis. The objective of this study was to investigate the relationship between CORT, insulin, prolactin, growth hormone, and insulin-like growth factor-1 in milk as well as the effect of CORT on the expression of receptors of insulin (INSR), prolactin (PRLR), growth hormone (GHR); we also studied the insulin-like growth factor-1 (IGF1R), glucocorticoid (NR3C1), mineralocorticoid (NR3C2), B-cell lymphoma 2 (BCL2), BCL-2-like protein X (BAX) genes, and the apoptosis rate of mammary epithelial cells of lactating Saanen goats in vivo and in vitro. The following experiments were conducted: (1) comparing hormone release in milk and blood after ACTH or a placebo administration; (2) evaluating the effect of acute CORT increases in mammary gland expression and milk yield in vivo; and (3) evaluating the effect of a chronic increase in CORT concentration in epithelial mammary cell apoptosis in vitro. In vivo, ACTH administration significantly increased CORT release but did not affect insulin, prolactin, growth hormone, and insulin-like growth factor-1 release in plasma and milk versus placebo. The results show also that a low CORT release after ACTH administration increased the expression of GHR and PRLR genes in the mammary tissue. Indeed, CORT release significantly increased the milk yield from goats subjected to ACTH versus goats subjected to the placebo. However, a higher amount of CORT added in vitro upregulated the NR3C1, GHR, PRLR, and BAX genes and downregulated the IGF1R and INSR genes, which could negatively modulate the apoptosis of mammary epithelial cells. Finally, the effect of CORT in vivo after ACTH administration demonstrated the increased expression of the PRLR and GHR genes, which may improve epithelial cell responsiveness and be associated with the positive effect of CORT observed on milk yield at mid-end lactation.

Survival outcomes, hematologic complications and growth impairment after sequential chemoradiotherapy in intracranial NGGCTs: aretrospective study.

This study aimed to evaluate the clinical features, prognostic factors, and survival outcomes for patients with intracranial nongerminomatous germ cell tumors (NGGCTs), with aparticular focus on treatment toxicity for long-term survivors. Intracranial NGGCTs treated with platinum-based chemotherapy and craniospinal irradiation (CSI) in our institution were retrospectively analyzed. Hematological complications following sequential chemoradiotherapy as well as height and weight in childhood survivors were evaluated. Plasma growth hormone (GH) concentrations prior to and after radiotherapy were obtained for the comparisons. Atotal of 111 intracranial NGGCTs were included. The 3‑year overall survival (OS) and event-free survival (EFS) rates were 83.5% ± 3.9% and 71.0% ± 4.8%, respectively. Acombined treatment modality consisting of ≥ 4cycles of platinum-based chemotherapy and CSI was associated with an improved OS (P = 0.003) and EFS (P < 0.001). Thrombocytopenia of any grade occurred in 35.4% (34/96) of patients, and the threshold age for an increased risk of thrombocytopenia was 14 years (area under the curve AUC = 0.752, P < 0.0001) as derived from receiver operating characteristic (ROC) analysis. Growth impediment was found in 8of 56(14%) patients. The age for receiving radiotherapy was found to inversely correlate with height development, revealing acut-off age of 11.5 years for risking growth impairment (AUC = 0.806, P = 0.004). Consistently, asignificant decline in plasma growth hormone after radiotherapy was observed in patients ≤ 11.5 years (P < 0.01) but not patients > 11.5 years. (P > 0.05). Our study suggested that acombined treatment modality with at least four cycles of chemotherapy and CSI was safe and effective for patients with intracranial NGGCTs. Radiotherapy should be used with caution for patients < 11.5 years due to growth impairment.

PSII-B-25 Age-related changes in growth hormone-insulin like growth factor 1 axis-regulating factors and metabolic hormones in Korean cattle steer

Abstract Meat yield is important for beef industry for maximum profits. Enhancing muscle growth by promoting hypertrophy of muscle fiber is required for increasing meat yield. Growth hormone (GH)-insulin like growth factor 1 (IGF1) axis and metabolic hormones have a central role for regulating hypertrophy of muscle fiber. We investigated age-related changes in GH-IGF1 axis-regulating factors and metabolic hormones in beef cattle. Ten Korean cattle steers were used. The longissimus thoracis (LT) samples were biopsied between the 11th and 12th rib at 12, 18, and 24 months of age. Steers were slaughtered at 34 month of age and the LT samples were collected. The LT samples were used for histological observation of muscle fiber size and detection of mRNA levels by real-time PCR analysis. Blood was collected at 12, 18, 24, and 34 months of age and used for hormone analyses. The mean muscle fiber size increased (P &amp;lt; 0.01) from 12 to 24 months, and remained unchanged at 34 months. Plasma GH concentrations were unchanged with age, whereas circulating IGF-1 concentrations decreased (P &amp;lt; 0.001) with age. Testosterone and insulin concentrations increased from 12 to 24 months and remained unchanged at 34 months. Leptin concentrations were unchanged from 12 to 24 months and increased at 34 months. The mRNA levels of growth hormone receptor (GHR) and signal transducer and activator of transcription 5a/b (STAT5a/b) decreased (P &amp;lt; 0.01) from 12 to 24 months, whereas mRNA levels of IGF-1 gene increased (P &amp;lt; 0.001) with age. Results indicate that the increased muscle fiber size in LT from 12 to 24 months are characterized with increasing concentrations of circulating testosterone and insulin. Age-dependent changes in muscle fiber hypertrophy were also related with changes in GHR, STAT5a/b, IGF-1 mRNA levels in the LT.

LIMITED INTRAVENOUS ACCESS: ROLE OF IM VASOPRESSIN IN VASODILATORY SHOCK

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Introduction:Vasopressin is an antidiuretic hormone analog that has become an important drug in the treatment of vasodilatory shock through its vasoconstrictive and water retention properties to maintain blood pressure. We present two cases of vasodilatory shock where intravenous access was limited and intramuscular (IM) vasopressin was used for management. CASE PRESENTATION: Patient 1: An 85 year old female with a medical history of hypertension and colon cancer presented with septic shock. She received dopamine via midline on the upper left arm to maintain blood pressure, with the patient's healthcare proxy refusing a central line. Multiple attempts to obtain venous access for a blood transfusion were unsuccessful. The dopamine drip could not be held due to severe hypotension. The decision was made to administer IM vasopressin (10 Units) to maintain blood pressure while stopping dopamine during the blood transfusion. The transfusion was completed over two hours and the blood pressure improved from 76/39 - 123/63. Patient 2: A 63 year old male with a medical history of smoking and peripheral vascular disease was admitted for tachycardia and hypoxia. He had necrotizing pneumonia and was in septic shock. He continued to be volume unresponsive despite intravenous fluid resuscitation. He was placed on a dopamine drip to maintain blood pressure and became tachycardic and remained in shock. Bedside ultrasound showed signs of volume overload. Twenty units of intramuscular vasopressin was given and blood pressure improved within 15 minutes and was maintained between 120/76-105/69 for 1.5 hours. DISCUSSION: Very frequently we encounter difficulties obtaining intravenous access while resuscitating a patient. Such situations pose an immense challenge in managing shock. Vasopressin is unique in its ability to be utilized intramuscularly.[1] Utilizing medications intramuscularly for urgent situations has a significant impact on management when there is limited, or lack of, intravenous access for hemodynamically unstable patients. The onset of action for vasopressin is approximately two hours, however our patient showed response within 15 minutes, demonstrating its potential.[1] After the initial onset of shock, endogenous stores of antidiuretic hormone are consumed and the vasodilatory mechanisms of shock may propagate.[3] Vasopressin itself may reverse some of the vasodilatory changes induced in shock, and in combination with other pressors may prove to be of greater benefit than that of pressors alone.[2] CONCLUSIONS: In the setting of shock with limited intravenous access, intramuscular vasopressin may be an effective option for initial stabilization until IV access is obtained. REFERENCE #1: Brostoff J, James VH, Landon J. Plasma corticosteroid and growth hormone response to lysine-vasopressin in man. J Clin Endocrinol Metab. 1968;28(4):511-518. REFERENCE #2: Forrest P. Vasopressin and shock. Anaesth Intensive Care. 2001;29(5):463-472. REFERENCE #3: Russell JA. Bench-to-bedside review: Vasopressin in the management of septic shock. Crit Care. 2011;15(4):226. DISCLOSURES: No relevant relationships by George Apergis, source=Web Response No relevant relationships by Dushyant Damania, source=Web Response No relevant relationships by Aaron Douen, source=Web Response No relevant relationships by Jean Mallipudi, source=Web Response No relevant relationships by George Mbolu, source=Web Response No relevant relationships by Ryan Panetti, source=Web Response

Relationship between Anthropometric, Physical and Hormonal Parameters among Pre-Pubertal Handball Players.

Background: The aims of our study were to investigate the changes in anthropometric and physical parameters and fasting hormonal levels among pre-pubertal female handball players (n = 14, age: 11.53 ± 0.58 yrs, height: 153.36 ± 5.12 cm, body mass: 43.59 ± 6.14 kg) in the pre-season period following 8 weeks of handball training, and to analyze the contribution of hormones, physical performance and anthropometric parameters. Methods: Prior to and immediately following the training period, several anthropometric, strength, and cardiorespiratory variables, including fasting hormonal concentrations (plasma cortisol, estradiol, testosterone and growth hormones) were measured. Athletes performed concurrent resistance and aerobic exercises, including game-based trainings during the 8-week training period. Results: Significant elevations were found in all strength parameters (maximal handgrip strength dominant (D): 16.40%, p < 0.01; non-dominant (ND): 25.15%, p < 0.05; maximal concentric (MVC) torque of quadriceps D: 13.82%, p < 0.05; ND: 12.61%, p < 0.05; MVC torque of hamstring D: 12.14%, p < 0.01; ND: 12.44%, p < 0.01), including plasma cortisol levels (C, 34.30%, p < 0.05) and peak respiratory quotient (5.24%, p < 0.05). Body composition and maximal oxygen uptake (VO2max) remained unchanged. Percentage changes in thigh (r = 0.316, p < 0.05), hand (r = 0.361, p < 0.05), and hip circumference (r = 0.297, p < 0.05) correlated with C changes. Percentage changes in plasma growth hormone levels (GH) contributed to the magnitude of gains in handgrip strength (r = 0.553, p < 0.05). Percentage changes in maximal exercise pulmonary ventilation (MVE) correlated with elevated C (r = −0.592, p < 0.05). Discussion: Changes in anthropometric variables and fasting hormone levels (estradiol, testosterone and cortisol) were poor indicators of developing VO2max and strength during pre-pubertal years. Physical adaptation may not be explained in consideration of the athletes’ hormonal or anthropometric characteristics. Conclusion: Gradually increased training volume followed by a summer break should be applied to youth handball, considering the anti-hypertrophic responses and the inhibitory effect of elevating C on pre-pubertal maturation.

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway.

Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates.Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60.Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml).Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.

Hormonal stress responses of growth hormone and insulin-like growth factor-I in highly resistance trained women and men

The purpose of this study was to examine the responses of growth hormone (GH) and insulin-like growth factor-I (IGFI) to intense heavy resistance exercise in highly trained men and women to determine what sex-dependent responses may exist. Subjects were highly resistance trained men (N = 8, Mean ± SD; age, yrs., 21 ± 1, height, cm, 175.3 ± 6.7, body mass, kg, 87.0 ± 18.5, % body fat, 15.2 ± 5.4, squat X body mass, 2.1 ± 0.4; and women (N = 7; Mean ± SD, age, yrs. 24 ± 5, height, cm 164.6 ± 6.7, body mass, kg 76.4 ± 8.8, % body fat, 26.9 ± 5.3, squat X body mass, 1.7 ± 0.6). An acute resistance exercise test protocol (ARET) consisted of 6 sets of 10 repetitions at 80% of the 1 RM with 2 min rest between sets was used as the stressor. Blood samples were obtained pre-exercise, after 3 sets, and then immediately after exercise (IP), 5, 15, 30, and 70 min post-exercise for determination of blood lactate (HLa), and plasma glucose, insulin, cortisol, and GH. Determination of plasma concentrations of IGFI, IGF binding proteins 1, 2, and 3 along with molecular weight isoform factions were determined at pre, IP and 70 min. GH significantly (P ≤ 0.05) increased at all time points with resting concentrations significantly higher in women. Significant increases were observed for HLa, glucose, insulin, and cortisol with exercise and into recovery with no sex-dependent observations. Women showed IGF-I values that were higher than men at all times points with both seeing exercise increases. IGFBP-1 and 2 showed increase with exercise with no sex-dependent differences. IGFBP-3 concentrations were higher in women at all-time points with no exercise induced changes. Both women and men saw an exercise induced increase with significantly higher values in GH in only the mid-range (30-60 kD) isoform. Only women saw an exercise induced increase with significantly higher values for IGF fractions only in the mid-range (30–60 kD) isoform, which were significantly greater than the men at the IP and 70 min post-exercise time points. In conclusion, the salient findings of this investigation were that in highly resistance trained men and women, sexual dimorphisms exist but appear different from our prior work in untrained men and women and appear to support a sexual dimorphism related to compensatory aspects in women for anabolic mediating mechanisms in cellular interactions.

Starvation-induced transcription factor CREBH negatively governs body growth by controlling GH signaling.

cAMP responsive element-binding protein H (CREBH) is a hepatic transcription factor to be activated during fasting. We generated CREBH knock-in flox mice, and then generated liver-specific CREBH transgenic (CREBH L-Tg) mice in an active form. CREBH L-Tg mice showed a delay in growth in the postnatal stage. Plasma growth hormone (GH) levels were significantly increased in CREBH L-Tg mice, but plasma insulin-like growth factor 1 (IGF1) levels were significantly decreased, indicating GH resistance. In addition, CREBH overexpression significantly increased hepatic mRNA and plasma levels of FGF21, which is thought to be as one of the causes of growth delay. However, the additional ablation of FGF21 in CREBH L-Tg mice could not correct GH resistance at all. CREBH L-Tg mice sustained GH receptor (GHR) reduction and the increase of IGF binding protein 1 (IGFBP1) in the liver regardless of FGF21. As GHR is a first step in GH signaling, the reduction of GHR leads to impairment of GH signaling. These data suggest that CREBH negatively regulates growth in the postnatal growth stage via various pathways as an abundant energy response by antagonizing GH signaling.

Lack of Brain Insulin Receptor Substrate-1 Causes Growth Retardation, With Decreased Expression of Growth Hormone-Releasing Hormone in the Hypothalamus.

Insulin receptor substrate-1 (Irs1) is one of the major substrates for insulin receptor and insulin-like growth factor-1 (IGF-1) receptor tyrosine kinases. Systemic Irs1-deficient mice show growth retardation, with resistance to insulin and IGF-1, although the underlying mechanisms remain poorly understood. For this study, we generated mice with brain-specific deletion of Irs1 (NIrs1KO mice). The NIrs1KO mice exhibited lower body weights, shorter bodies and bone lengths, and decreased bone density. Moreover, the NIrs1KO mice exhibited increased insulin sensitivity and glucose utilization in the skeletal muscle. Although the ability of the pituitary to secrete growth hormone (GH) remained intact, the amount of hypothalamic growth hormone-releasing hormone (GHRH) was significantly decreased and, accordingly, the pituitary GH mRNA expression levels were impaired in these mice. Plasma GH and IGF-1 levels were also lower in the NIrs1KO mice. The expression levels of GHRH protein in the median eminence, where Irs1 antibody staining is observed, were markedly decreased in the NIrs1KO mice. In vitro, neurite elongation after IGF-1 stimulation was significantly impaired by Irs1 downregulation in the cultured N-38 hypothalamic neurons. In conclusion, brain Irs1 plays important roles in the regulation of neurite outgrowth of GHRH neurons, somatic growth, and glucose homeostasis.

Circulating levels of growth hormone in postural orthostatic tachycardia syndrome

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case–control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 years; n = 46). Plasma GH levels were measured using high-sensitivity chemiluminescence sandwich immunoassay. The burden of orthostatic intolerance symptoms was assessed by the Orthostatic Hypotension Questionnaire (OHQ), consisting of a symptom assessment scale (OHSA) and a daily activity scale (OHDAS). POTS patients had significantly higher composite OHQ score than controls, more symptoms and less activity. Supine heart rate and diastolic blood pressure (BP), but not systolic BP, were significantly higher in POTS. Median plasma GH levels were significantly lower in POTS (0.53 ng/mL) than controls (2.33 ng/mL, p = 0.04). GH levels were inversely related to OHDAS in POTS and supine systolic BP in POTS and controls, but not heart rate neither group. POTS is associated with lower GH levels. Impairment of daily life activities is inversely related with GH in POTS. A higher supine diastolic BP is inversely associated with GH levels in POTS and healthy individuals.

A Mathematical Model For The Special Effects Of Phosphatidylserine On Endocrine Reaction To Reasonable Concentration Exercise In Healthy Male Subjects

In this study, we implement a three-parameter Weibull-G exponential model analysis to analyse the impact of short-range supplementation with a modest dosage of cortisol, lactate, growth hormone and testosterone plasma attentions in healthy male profiles before, during, and after moderate intensity practice.PS supplementation facilitates a desirable athlete state of hormones through stepping up at the rates of cortisol. Ultimately, we conclude that the application part coincides with a mathematical model and the result is linked to the medical report. In the future, this paper will be very beneficial in the medicinal field.

Effects of long-term cortisol treatment on growth and osmoregulation of Atlantic salmon and brook trout

Cortisol is the final product of the hypothalamic-pituitary-interrenal (HPI) axis and acts as a gluco- and mineralo-corticoid in fish. Long-term elevations of cortisol have been linked to reduced growth in fishes, but the mechanism(s) and relative sensitivities of species are still unclear. We carried out experiments to examine the relative effects of cortisol on growth and gill NKA activity in two salmonids: Atlantic salmon (Salmo salar) and brook trout (Salvelinus fontinalis). Treatment with intraperitoneal cortisol implants for 30 days resulted in reduced growth in both species, but with greater sensitivity to cortisol in brook trout. Gill NKA activity was strongly upregulated by cortisol in Atlantic salmon, and weakly upregulated in brook trout but with no statistically significant effect. Cortisol treatment resulted in reduced plasma levels of insulin-like growth factor I and increased plasma growth hormone levels in Atlantic salmon. Our results demonstrate that there are species differences in the sensitivity of growth and osmoregulation to cortisol, even among species in the same family (Salmonidae).

Delayed Postnatal Growth and Anterior Pituitary Development in Growth-Retarded (grt) Female Mice.

Growth-retarded (grt) mice display primary congenital hypothyroidism due to the hyporesponsiveness of their thyroid glands to thyroid-stimulating hormone (TSH). We examined somatic growth, anterior pituitary development, and hormonal profiles in female grt mice and normal ones. Although growth in grt females was suppressed 2 weeks after birth, the measured growth parameters and organ weights gradually increased and finally reached close to the normal levels. Grt mice exhibited delayed eye and vaginal openings and remained in a state of persistent diestrus thereafter, plasma estrogen levels being lower than those in normal mice. Grt mice that received normal-donor thyroids showed accelerated growth and their body weights increased up to the sham-normal levels, indicating the importance of early thyroid hormone supplementation. In the anterior pituitary, there were fewer growth hormone (GH) and prolactin (PRL) cells in grt mice than in normal mice as examined at 12 weeks after birth, but the numbers of these cells did not differ from those in normal mice after 24 weeks. Grt mice had more TSH cells than normal mice until 48 weeks. Plasma GH levels in grt mice were lower than those in normal mice at 2 weeks, but did not differ substantially after 5 weeks. Compared with normal mice, grt mice had significantly lower plasma PRL and thyroxine levels, but notably higher TSH levels until 48 weeks. These findings indicate that thyroid hormone deficiency in grt mice causes delayed development and growth, and inappropriate development of GH, PRL and TSH cells, followed by the abnormal secretion of hormones by these pituitary cells.

Evaluation of hypophysectomy for treatment of hypersomatotropism in 25 cats.

BackgroundSuccessful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats.ObjectivesTo describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020.AnimalsTwenty‐five client‐owned cats with spontaneous hypersomatotropism.MethodsRetrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin‐like growth factor‐1 (IGF‐1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF‐1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow‐up information from owners and referring veterinarians.ResultsMedian postoperative hospital stay was 7 days (range, 3‐18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0‐101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6‐13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF‐1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14‐240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900‐1794 days; range, 11‐3180 days) and the overall 1‐, 2‐, and 3‐year all‐cause survival rates were 76%, 76%, and 52%, respectively.Conclusions and Clinical ImportanceThis study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure.

Metabolic and hormonal control of energy utilization and partitioning from early to mid lactation in Sarda ewes and Saanen goats

In a recent study, we observed that starch-rich diets used in mid lactation induced lower milk production persistency and higher body fat accumulation in dairy ewes compared with dairy goats. Because these species differences could be linked to hormonal mechanisms that drive energy partitioning, in the same experiment, we explored the evolution of metabolic and hormonal status during lactation to test this hypothesis. Twenty mature Sarda dairy ewes and 20 mature Saanen goats [15-134 ± 11 d in milk (DIM), mean ± SD] were compared simultaneously. In early lactation, each species was allocated to one dietary treatment: high-starch diet [HS: 20.4% starch, on dry matter (DM) basis], whereas from 92 ± 11 DIM, each species was allocated to 1 of 2 dietary treatments: HS (20.0% starch, on DM basis) and low-starch (LS: 7.8% starch, on DM basis) diets. Blood samples were collected in the morning to analyze glucose, nonesterified fatty acids (NEFA), growth hormone (GH), insulin, and insulin-like growth factor I (IGF-I). Data were analyzed using the PROC MIXED procedure of SAS with repeated measurements (SAS Version 9.0). The HS and LS diets applied in mid lactation did not affect metabolic status of the animal within species; thus, only a comparison between species was carried out. From early to mid lactation, plasma glucose concentration was higher in ewes than in goats (54.57 vs. 48.35 ± 1.18 mg/dL), whereas plasma NEFA concentration was greater in goats than in ewes (0.31 vs. 0.25 ± 0.03 mmol/L). Goats had higher plasma GH concentration and lower plasma insulin content than ewes (4.78 vs. 1.31 ng/mL ± 0.47; 0.11 vs. 0.26 μg/L ± 0.02). Plasma IGF-I concentration did not vary between species. The comparison of metabolic and hormonal status of lactating Sarda dairy ewes and Saanen goats, carried out by studying simultaneously the 2 species in the same stage of lactation and experimental conditions, suggests that the higher insulin and glucose concentration observed in Sarda ewes explains why they partitioned more energy toward body reserves than to the mammary gland, especially in mid lactation. This can justify the negative effect of high-starch diets in mid-lactating Sarda ewes. Conversely, the highest GH and NEFA concentration observed in Saanen goats explain why they partitioned more energy of starch diets toward the mammary gland than to body reserves and justify the positive effect of high-starch diet in mid lactation. Together, these different responses contribute to explain why specialized dairy goats, such as the Saanen breed, have a higher milk production persistency than specialized dairy sheep breeds, such as the Sarda.

Interactive Effects of Copper Sources and a High Level of Phytase in Phosphorus-Deficient Diets on Growth Performance, Nutrient Digestibility, Tissue Mineral Concentrations, and Plasma Parameters in Nursery Pigs

The present study investigated the interactive effects of copper sources and a high level of phytase on growth performance, nutrient digestibility, tissue mineral concentrations, and plasma parameters in nursery pigs. Weaning piglets (N = 192; 6.06 ± 0.99 kg), blocked by body weight, were randomly allotted to 1 of 4 dietary treatments, with 12 pens per treatment and 4 pigs per pen. A basal diet for each phase was formulated to meet nutrient requirements for nursery pigs with the exception that standardized total tract digestibility (STTD) P was reduced by 0.12% and Ca was adjusted to achieve Ca/STTD P = 2.15. The 4 dietary treatments were arranged in a 2 × 2 factorial design, with 2 Cu sources (125 mg/kg Cu from copper methionine hydroxy analogue chelate (Cu-MHAC) or copper sulfate (CuSO4)) and 2 phytase levels (0 or 1500 phytase units (FTU)/kg). Results showed that there was an interaction (P < 0.05) between Cu sources and phytase on ADG during days 0–41. When phytase was not present in the diets (P deficient), there was no difference between the two Cu sources in terms of ADG during days 0–41, whereas with phytase in the diets, Cu-MHAC tended to improve (P < 0.10) ADG during days 0–41 compared with CuSO4. Pigs fed Cu-MHAC had greater apparent total tract digestibility (ATTD) of neutral and acid detergent fiber and STTD of P than those fed CuSO4. Phytase increased (P < 0.05) growth performance, ATTD of Ca and P, and plasma inositol and growth hormone concentrations. In conclusion, Cu-MHAC may be more effective in improving growth rate than CuSO4 when phytase was supplemented at 1500 FTU/kg. Cu-MHAC enhanced fiber and P digestibility regardless of phytase, compared with CuSO4. Phytase addition in P-deficient diets was effective in improving growth performance, Ca and P digestibility, and plasma inositol and growth hormone concentrations.

Pharmacological profile and clinical efficacy of anamorelin HCl (ADLUMIZ&lt;sup&gt;®&lt;/sup&gt;Tablets), the first orally available drug for cancer cachexia with ghrelin-like action in Japan

Anamorelin hydrochloride (hereinafter referred to as anamorelin) is an orally active, small-molecule drug with a similar pharmacological action to ghrelin, an endogenous ligand of growth hormone secretagogue receptor type 1a (GHS-R1a). It was first approved in Japan for the treatment of cancer cachexia, characterized by weight loss and anorexia. Anamorelin stimulated the secretion of growth hormone (GH) from cultured rat pituitary cells and increased plasma GH levels by oral administration to rats, pigs and humans. When anamorelin was orally administered once daily for 6 days to rats, larger body weight gain associated with increased food consumption compared to the control group was observed from after the first dose. Anamorelin is a selective agonist for GHS-R1a and enhanced GHS-R1a-mediated pituitary GH secretion and increased food consumption, resulting in body weight gain. In the two Japanese phase II studies in patients with cancer cachexia associated with non-small cell lung cancer (NSCLC), improvement of lean body mass (LBM) and body weight losses and anorexia were demonstrated. The tumor types of target patients in the Japanese phase III study were colorectal, gastric, and pancreatic cancer. As a result, maintenance and increase of LBM and body weight as well as improvement of anorexia were observed, and the efficacy against cancer cachexia associated with colorectal, gastric, and pancreatic cancer was confirmed. There were no observed events considered to be significant safety risks. In conclusion, anamorelin is expected to provide a new therapeutic option for cancer cachexia for which no effective treatment has been available.

Physiological Effects of Water Flow Induced Swimming Exercise in Seabream Sparus aurata.

A longer on-land rearing period of Gilthead seabream Sparus aurata before transfer to sea-cages would allow the farmer to benefit from exercise-enhanced growth, resilience, and robustness as induced by increasing water flow in the tanks. In this study, the physiological effects of flow-conditioning were investigated by subjecting large groups of experimental fish to minimal flow or to flow regimes inducing swimming exercise at 1 or 2 body length (BL) s−1 for a period of 8 months (February–October) in 1,500 L tanks. Fish representing the three treatment groups were then used for: (1) a stress challenge netting test and plasma cortisol measurement (baseline, peaking, and recovery levels), (2) blood plasma measurements of glucose, triglycerides, lactate, cholesterol, growth hormone (GH), and insulin-like growth factor 1 (IGF1), and (3) heart and muscle gene expression of the GH and IGF1 receptors and the muscle transcriptome by deep RNA sequencing (RNAseq). Fish size after 8 months of flow conditioning was 92 ± 27 g body weight (BW) for fish under minimal flow, 106 ± 24 g BW (+15%) at 1 BL s−1, and 125 ± 27 g BW (+36%) at 2 BL s−1. Flow conditioning at 1 BL s−1 provided optimal conditions for growth and uniformity, but also stress (lowest baseline plasma cortisol), robustness (higher condition factor and larger hearts), and energy mobilization (increased plasma glucose). Although flow enhanced growth linearly with swimming speed, also the percentage of lordotic fish increased with exercise, particularly high for swimming at 2 BL s−1. The absence of important differences in plasma GH and IGF1, and expression levels of their receptors in heart and white skeletal muscle, indicated that other factors may be involved in growth enhancement. RNAseq of the white skeletal muscle showed upregulated expression of genes involved in muscle contraction, muscle development and its molecular regulation, and immune genes that may play a role in the muscle repair mechanism. An exercise regime of swimming at 1 BL s−1 can be considered as optimal for farming robust seabream although the increase of skeletal deformities should be avoided.

Photoperiodic regulation of pituitary thyroid-stimulating hormone and brain deiodinase in Atlantic salmon

Seasonal timing is important for many critical life history events of vertebrates, and photoperiod is often used as a reliable seasonal cue. In mammals and birds, it has been established that a photoperiod-driven seasonal clock resides in the brain and pituitary, and is driven by increased levels of pituitary thyroid stimulating hormone (TSH) and brain type 2 iodothyronine deiodinase (DIO2), which leads to local increases in triiodothyronine (T3). In order to determine if a similar mechanism occurs in fish, we conducted photoperiod manipulations in anadromous (migratory) Atlantic salmon (Salmo salar) that use photoperiod to time the preparatory development of salinity tolerance which accompanies downstream migration in spring. Changing daylength from short days (light:dark (LD) 10:14) to long days (LD 16:8) for 20 days increased gill Na+/K+-ATPase (NKA) activity, gill NKAα1b abundance and plasma growth hormone (GH) levels that normally accompany increased salinity tolerance of salmon in spring. Long-day exposure resulted in five-fold increases in pituitary tshβb mRNA levels after 10 days and were sustained for at least 20 days. tshβb mRNA levels in the saccus vasculosus were low and not influenced by photoperiod. Increased daylength resulted in significant increases in dio2b mRNA levels in the hypothalamus and midbrain/optic tectum regions of the brain. The results are consistent with the presence of a photoperiod-driven seasonal clock in fish which involves pituitary TSH, brain DIO2 and the subsequent production of T3, supporting the hypothesis that this is a common feature of photoperiodic regulation of seasonality in vertebrates.

Association between Growth Hormone and Insulin-like Growth Factor-1 (IGF-1) Levels, Liver Function and Short-Term Survival of Paediatric Liver Recipients

The growth hormone/insulin-like growth factor-1 (IGF-1) system is an important humoral mediator of liver function with an inherent potential for assessing liver condition and survival prognosis following liver transplantation (LT). Aim . Analysis of associations between growth hormone and IGF-1 levels in blood and markers of liver function and post-LT survival in children. Materials and methods . We examined 143 children with end-stage liver disease (ESLD) aged 3 to 73 (median 8) months after related LT. The growth hormone and IGF-1 concentrations in plasma were evaluated in ELISA assays. Results . In children with ESLD, concentrations of growth hormone and IGF-1 were significantly higher and lower, respectively, compared to healthy children of the same age ( p <0.01). Compared to the level of growth hormone, the level of IGF-1 was related to the diagnosis ( r = 0.30, p = 0.004). IGF-1 shows lower concentrations in biliary atresia and other cholestatic liver diseases compared to non-cholestatic aetiologies (4.7 (0.0—23.4) and 42.3 (9.0—55.0) ng/mL, respectively, p = 0.03). The growth hormone level directly correlated with the severity of liver fibrosis ( r = 0.47, p = 0.02). It was higher in fibrosis grade 4 (F4) than in F1—F3 (4.7 (2.1—7.2) and 2.1 (1.2—3.3) ng/mL, respectively, p = 0.02). Hormone levels normalised after LT. Unlike IGF-1, the level of growth hormone correlated one month after LT with the 6-months survival rate of recipients ( r = 0.36, p = 0.01) being significantly lower in survivors compared to patients who did not survive this period (1.3 (0.5—1.9) and 2.9 (1.6—12.4) ng/mL, respectively, p = 0.02). Conclusion . Blood levels of growth hormone and IGF-1 were shown to differ significantly between ESLD and healthy children, correlating with fibrosis severity and disease aetiology. The level of growth hormone in the blood of LT recipients associates with a short-term survival rate.