Domestic Animal Endocrinology - Articles in Press

Oxyntomodulin increases the concentrations of insulin and glucose in plasma but does not affect ghrelin secretion in Holstein cattle under normal physiological conditions - Corrected Proof

S. ThanThan, H. Zhao, S. Yannaing, T. Ishikawa, H. Kuwayama — 2010-08-13

Abstract: Ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R1a), has been shown to stimulate growth hormone (GH) secretion. Regulation of ghrelin secretion in ruminants is not well studied. We investigated the effects of oxyntomodulin (OXM) and secretin on the secretions of ghrelin, insulin, glucagon, glucose, and nonesterified fatty acids (NEFA) in pre-ruminants (5 wk old) and ruminants (10 wk old) under normal physiological (feeding) conditions. Eight male Holstein calves (pre-ruminants: 52 ± 1 kg body weight [BW]; and ruminants: 85 ± 1 kg BW) were injected intravenously with 30 μg of OXM/kg BW, 50 μg of secretin/kg BW, and vehicle (0.1% bovine serum albumin [BSA] in saline as a control) in random order. Blood samples were collected, and plasma hormones and metabolites were analyzed using a double-antibody radioimmunoassay system and commercially available kits, respectively. We found that OXM increased the concentrations of insulin and glucose but did not affect the concentrations of ghrelin in both pre-ruminants and ruminants and that there was no effect of secretin on the concentrations of ghrelin, insulin, and glucose in these calves. We also investigated the dose-response effects of OXM on the secretion of insulin and glucose in 8 Holstein steers (401 ± 1 d old, 398 ± 10 kg BW). We found that OXM increased the concentrations of insulin and glucose even at physiological plasma concentrations, with a minimum effective dose of 0.4 μg/kg for the promotion of glucose secretion and 2 μg/kg for the stimulation of insulin secretion. These findings suggest that OXM takes part in glucose metabolism in ruminants.

Measuring cortisol in hair and saliva from dogs: coat color and pigment differences - Corrected Proof

A. Bennett, V. Hayssen — 2010-08-13

Abstract: Cortisol concentrations are frequently measured from a variety of sources including blood, saliva, urine, and feces to quantify stress in dogs. However, a need still exists for less intrusive collection methods in domestic animals and for more efficient means of measuring basal cortisol. The objectives of the present study were to minimize restraint for saliva sampling, to validate hair for basal cortisol measurement in dogs, and to determine concentrations of cortisol within the hair shaft and in relation to hair color. Using food luring, 79% of dogs required no restraint for saliva collection. Salivary and hair cortisol concentrations were positively correlated (P = 0.001), thus validating hair as a medium for basal cortisol quantification. Black dogs had less cortisol than nonblack dogs (P = 0.039) in hair, but not saliva. Across dogs, the average amount of cortisol did not differ between proximal and distal hair sections (P = 0.348). However, for 7 of the 9 dogs, more cortisol was present in the distal portions of the hair. We observed a difference in cortisol concentrations among hairs of different colors from individual dogs (P = 0.001). From the same 7 × 7 cm ischiatic patch from the same dog, black (eumelanin) hairs were consistently lower in cortisol than yellow (pheomelanin) hairs, and cortisol concentrations of agouti hairs were intermediate. This is the first evidence that hair of different colors might sequester cortisol differently.

Expression of mRNA for proglucagon and glucagon-like peptide-2 (GLP-2) receptor in the ruminant gastrointestinal tract and the influence of energy intake - Corrected Proof

2010-08-06

Abstract: Glucagon-like peptide-2 (GLP-2) is a potent trophic gut hormone, yet its function in ruminants is relatively unknown. Experiment 1 was conducted as a pilot study to establish the presence of GLP-2 in ruminants and to ascertain whether it was responsive to increased nutrition, as in non-ruminants. Concentrations of intact GLP-2 in the blood and gut epithelial mRNA expression of proglucagon (GCG) and the GLP-2 receptor (GLP2R) were measured in 4 ruminally, duodenally, and ileally cannulated steers. Steers were fed to meet 0.75 × NEM for 21 d, and then increased to 1.75 × NEM requirement for another 29 d. Blood samples and ruminal, duodenal, and ileal epithelium biopsies were collected at low intake (Days −6 and −3), acute high intake (Days 1 and 3), and chronic high intake (Days 7 and 29) periods. Experiment 2 investigated the mRNA expression pattern of GCG and GLP2R in epithelial tissue obtained from the forestomachs (rumen, omasum, and abomasum) and intestines (duodenum, jejunum, ileum, and colon) of 18 forage-fed Angus steers (260 kg BW). In Experiments 1 and 2, real-time polymerase chain reaction showed that expression of GCG and GLP2R mRNA was detectable in forestomach tissues, but expression was greater (P < 0.001) in small intestinal and colon tissue. High energy intake tended (P = 0.07) to increase plasma GLP-2 during the acute period and was paralleled by a 78% increase (P = 0.07) in ileal GCG mRNA expression. After this initial adaptation, duodenal GCG mRNA expression increased (P = 0.08) during the chronic high intake period. Duodenal GLP2R mRNA expression was not affected by energy intake, but ileal GLP2R expression was increased after 29 d of high energy intake compared to both the low and acute high intake periods (P = 0.001 and P = 0.01, respectively). These data demonstrate that cattle express GCG and GLP2R mRNA primarily in small intestinal and colon tissues. Increased nutrient intake increases ileal GCG mRNA and plasma GLP-2, suggesting that GLP-2 may play a role in the trophic response of the ruminant gastrointestinal tract to increased feed intake.

Effect of hyperlipidemia on 11β-hydroxysteroid-dehydrogenase, glucocorticoid receptor, and leptin expression in insulin-sensitive tissues of cats - Corrected Proof

2010-08-06

Abstract: Glucocorticoid (GC) action depends on GC plasma concentration, cellular GC receptor expression, and the pre-receptor hormone metabolism catalyzed by 11β-hydroxysteroid dehydrogenase (11β-HSD). 11β-Hydroxysteroid dehydrogenase exists in 2 isoforms; 11β-HSD1 converts inactive cortisone to cortisol, and 11β-HSD2 converts cortisol to cortisone. Increasing evidence in humans and experimental animals suggests that altered tissue cortisol metabolism may predispose to diabetes mellitus (DM). Once DM is established, hyperglycemia and hyperlipidemia may further maintain the abnormal metabolism of cortisol. To gain further insight in this regard, healthy cats were infused for 10 d with lipids (n = 6) or saline (n = 5). At the end of the infusion period, tissue samples from adipose tissue (visceral, subcutaneous), liver, and muscle were collected to determine mRNA expression of 11β-HSD1, 11β-HSD2, and GC receptor by real-time reverse-transcriptase polymerase chain reaction; blood samples were collected to determine plasma cortisol and leptin concentrations. Lipid infusion resulted in greater 11β-HSD1 expression and lower GC receptor expression in visceral and subcutaneous adipose tissue, and lower 11β-HSD2 expression in visceral adipose tissue and liver. Plasma cortisol did not differ. Leptin and body weight increased in lipid-infused cats. In spite of comparable circulating cortisol levels, up-regulation of 11β-HSD1 and down-regulation of 11β-HSD2 expression may result in increased tissue cortisol concentrations in fat depots of hyperlipidemic cats. Down-regulation of GC receptor may represent a self-protective mechanism against increased tissue cortisol levels. In conclusion, hyperlipidemia has a profound effect on 11β-HSD expression and supports the connection between high lipid concentrations and tissue cortisol metabolism.

Basal measures of insulin sensitivity and insulin secretion and simplified glucose tolerance tests in dogs - Corrected Proof

K.R. Verkest, L.M. Fleeman, J.S. Rand, J.M. Morton — 2010-08-05

Abstract: There is need for simple, inexpensive measures of glucose tolerance, insulin sensitivity, and insulin secretion in dogs. The aim of this study was to estimate the closeness of correlation between fasting and dynamic measures of insulin sensitivity and insulin secretion, the precision of fasting measures, and the agreement between results of standard and simplified glucose tolerance tests in dogs. A retrospective descriptive study using 6 naturally occurring obese and 6 lean dogs was conducted. Data from frequently sampled intravenous glucose tolerance tests (FSIGTTs) in 6 obese and 6 lean client-owned dogs were used to calculate HOMA, QUICKI, fasting glucose and insulin concentrations. Fasting measures of insulin sensitivity and secretion were compared with MINMOD analysis of FSIGTTs using Pearson correlation coefficients, and they were evaluated for precision by the discriminant ratio. Simplified sampling protocols were compared with standard FSIGTTs using Lin's concordance correlation coefficients, limits of agreement, and Pearson correlation coefficients. All fasting measures except fasting plasma glucose concentration were moderately correlated with MINMOD-estimated insulin sensitivity (|r| = 0.62–0.80; P < 0.03), and those that combined fasting insulin and glucose were moderately closely correlated with MINMOD-estimated insulin secretion (r = 0.60–0.79; P < 0.04). HOMA calculated using the nonlinear formulae had the closest estimated correlation (r = 0.77 and 0.74) and the best discrimination for insulin sensitivity and insulin secretion (discriminant ratio 4.4 and 3.4, respectively). Simplified sampling protocols with half as many samples collected over 3 h had close agreement with the full sampling protocol. Fasting measures and simplified intravenous glucose tolerance tests reflect insulin sensitivity and insulin secretion derived from frequently sampled glucose tolerance tests with MINMOD analysis in dogs.

Effect of recombinant human TSH on the uptake of radioactive iodine (123I) by the thyroid gland in healthy beagles - Corrected Proof

2010-08-05

Abstract: In human medicine, recombinant human thyroid-stimulating hormone (rhTSH) increases thyroid radioactive iodine uptake (RAIU), allowing radioiodine-131 (131I) dose reduction and greater efficacy in the treatment of differentiated thyroid cancer and multinodular goiter. The goal of this study was to evaluate the effect of rhTSH, administered 24 h and 48 h before radioiodine-123 (123I), on the thyroid RAIU in healthy dogs. Seven healthy euthyroid beagles were randomly allocated to 3 groups (2 groups of 2 dogs and 1 group of 3 dogs) in a prospective, blinded, crossover study. At Week 1, 1 group received 123I for a baseline RAIU; 1 group received 100 μg of rhTSH IV 24 h before 123I, and 1 group received 100 μg of rhTSH IV 48 h before 123I. All dogs received 37 MBq of radioactive 123I IV, and thyroid RAIU was determined 8 h, 24 h, and 48 h thereafter. The study was designed in such a manner that each dog received the 3 treatments and a wash-out period of 3 wk was respected in between. Blood samples were taken for measurement of serum total thyroxine (TT4) and thyrotropin (TSH) concentrations at baseline and 6 h, 12 h, 24 h, and 48 h after rhTSH administration. Recombinant human TSH caused no significant change on thyroid RAIU. The overall mean thyroid RAIU significantly decreased during the study independent of the treatment. Recombinant human TSH significantly increased serum TT4 concentration, which peaked 6 h after rhTSH administration. Compared to baseline, serum TSH concentration remained higher at 6 h, 12 h, 24 h, and 48 h. However, a statistically significant difference was reached only at 6 h and 12 h after rhTSH administration. No adverse effects of rhTSH were observed during the study. Further studies are needed to determine the best timing and dosage of administration of rhTSH in healthy and thyroid carcinoma dogs.

Cortisol release, heart rate, and heart rate variability in transport-naive horses during repeated road transport - Corrected Proof

A. Schmidt, S. Hödl, E. Möstl, J. Aurich, J. Müller, C. Aurich — 2010-08-05

Abstract: Domestic animals are often repeatedly exposed to the same anthropogenic stressors. Based on cortisol secretion and heart rate, it has been demonstrated that transport is stressful for horses, but so far, changes in this stress response with repeated road transport have not been reported. We determined salivary cortisol concentrations, fecal cortisol metabolites, cardiac beat-to-beat (RR) interval, and heart rate variability (HRV) in transport-naive horses (N = 8) transported 4 times over a standardized course of 200 km. Immunoreactive salivary cortisol concentrations always increased in response to transport (P < 0.001), but cortisol release decreased stepwise with each transport (P < 0.05). Concentrations of fecal cortisol metabolites increased from 55.1 ± 4.6 ng/g before the first transport to 161 ± 17 ng/g the morning after (P < 0.001). Subsequent transport did not cause further increases in fecal cortisol metabolites. In response to the first transport, mean RR interval decreased with loading of the horses and further with the onset of transport (1551 ± 23, 1304 ± 166, and 1101 ± 123 msec 1 d before, immediately preceeding, and after 60–90 min of transport, respectively; P < 0.05). Decreases in RR interval during subsequent transports became less pronounced (P < 0.001). Transport was associated with a short rise in the HRV variable standard deviation 2 (P < 0.001 except transport 1), indicating sympathetic activation. No consistent changes were found for other HRV variables. In conclusion, a transport-induced stress response in horses decreased with repeated transport, indicating that animals habituated to the situation, but an increased cortisol secretion remained detectable.

Progesterone concentration, estradiol pretreatment, and dose of gonadotropin-releasing hormone affect gonadotropin-releasing hormone-mediated luteinizing hormone release in beef heifers - Corrected Proof

F.C.F. Dias, M.G. Colazo, J.P. Kastelic, R.J. Mapletoft, G.P. Adams, J. Singh — 2010-06-28

Abstract: We examined whether progesterone (P4)-induced suppression of LH release in cattle can be overcome by an increased dose of exogenous gonadotropin-releasing hormone (GnRH) or pretreatment with estradiol (E2). In Experiment 1, postpubertal Angus-cross heifers (N = 32) had their 2 largest ovarian follicles ablated 5 d after ovulation. Concurrently, these heifers were all given a once-used, intravaginal P4-releasing insert (CIDR), and they were randomly assigned to be given either prostaglandin F2α (Low-P4) or no treatment (High-P4) at follicle ablation, and 12 h later. Six days after emergence of a new follicular wave, half of the heifers in each group (n = 8) were given either 100 or 200 μg of GnRH i.m. Plasma luteinizing hormone (LH) concentrations were higher in the Low- vs High-P4 groups, and in heifers given 200 vs 100 μg of GnRH (mean ± SEM 15.4 ± 2.2 vs 9.1 ± 1.2, and 14.8 ± 2.1 vs 9.8 ± 1.4 ng/mL, respectively; P ≤ 0.01). Ovulation rate was higher (P = 0.002) in the Low-P4 group (15/16) than in the High-P4 group (6/16), but it was not affected by GnRH dose (P = 0.4). In Experiment 2, heifers (n = 22) were treated similarly, except that 5.5 d after wave emergence, half of the heifers in each group were further allocated to be given either 0.25 mg estradiol benzoate i.m. or no treatment, and 8 h later, all heifers were given 100 μg GnRH i.m. Both groups treated with E2 (Low- and High-P4) and the Low-P4 group without E2 had higher peak plasma LH concentrations compared to the group with high P4 without E2 (12.6 ± 1.8, 10.4 ± 1.8, 8.7 ± 1.3, and 3.9 ± 1.2 ng/mL, respectively; (P < 0.04)). However, E2 pretreatment did not increase ovulation rates in response to GnRH (P = 0.6). In summary, the hypotheses that higher doses of GnRH will be more efficacious in inducing LH release and that exogenous E2 will increase LH release following treatment with GnRH were supported, but neither significantly increased ovulation rate.