T. S. Rumsey

Nutritional Modulation of Somatotropic Axis-cytokine Relationships in Cattle: A Brief Review

The objective of this review is to summarize data on the interrelationships that exist between nutrition, the endocrine system and their modulation of plasma tumor necrosis factor-alpha responses to endotoxin in cattle. During stress, intake of nutrients often is compromised and a percentage of available nutrients are diverted away from growth processes to stabilize other physiological processes of a higher survival priority. Management practices that minimize the magnitude and duration of disease stress will aid in speeding the return to homeostatic equilibrium. However, the shift away from growth during stress is almost inevitable as a mechanism to survive. Some degree of control and management of the metabolic cost of disease stress involves understanding the integration of nutritional, endocrine and immune signals by cells and working with the natural homeostatic processes. Endocrine hormones and immune system cytokine signals participate in redirecting nutrient use during disease stress. In an intricate interplay, hormones and cytokines regulate, modify and modulate each others production and tissue interactions to alter metabolic priorities. Levels of dietary protein and energy intake affect patterns of hormones and cytokines in the blood after endotoxin challenge and further modulate the biological actions of many of these regulatory effectors. In vivo, administration of growth hormone to young calves has significant effects to decrease the many specific physiological responses to endotoxemia. Many aspects of nutrition can attenuate or facilitate this effect.

Relationships between the thyroid and somatotropic axes in steers I: Effects of propylthiouracil-induced hypothyroidism on growth hormone, thyroid stimulating hormone and insulin-like growth factor I

The effects of propylthiouracil (PTU)-induced thyroid hormone imbalance on GH, TSH and IGF-I status in cattle were examined. In the first study, four crossbred steers (avg wt 350 kg) were fed a diet dressed with PTU (0, 1, 2 or 4 mg/kg/d BW) in a Latin square design with four 35-d periods. On day 29 in each period, steers were challenged with an intrajugular bolus of thyrotropin releasing hormone (TRH, 1.0 microgram/kg). Blood samples were obtained to assess the change in plasma GH and TSH as affected by PTU. Plasma IGF-I was measured from blood samples obtained before and after (every 6 hr for 24 hr) intramuscular injection of bovine GH (0.1 mg/kg, day 31). Doses of 1 and 2 mg/kg PTU increased plasma T4 (P < .01). At 4 mg/kg, PTU depressed T4 concentrations to 30% of control (P < .01). Plasma T3 linearly decreased with increasing doses of PTU (P < .01). Plasma TSH increased when PTU was fed at 4 mg/kg (P < .05) while the TSH response to TRH declined with increasing PTU (P < .02). Neither basal nor TRH-stimulated plasma concentration of GH was affected by PTU; the IGF-I response to GH tended to increase at the 1 and 2 mg/kg PTU (P < .01). In a second study 24 crossbred steers were fed PTU (1.5 mg/kg) for 119 d in a 2 x 2 factorial design with implantation of the steroid growth effector, Synovex-S (200 mg progesterone + 20 mg estradiol), as the other main effect. Basal plasma GH and IGF-I were not affected by PTU treatment. Synovex increased plasma concentration (P < .01) of IGF-I without an effect on plasma GH. The data suggest that mild changes in thyroid status associated with PTU affects regulation of T3, T4 and TSH more than GH or IGF-I in steers.

Relationships between the thyroid and somatotropic axes in steers. II: Effects of thyroid status on plasma concentrations of insulin-like growth factor I (IGF-I) and the IGF-I response to growth hormone.

Three studies assessed the effect of thyroid status on regulation of plasma IGF-I in cattle. First, four Angus-Hereford steers (av wt 345 kg) were fed 4 mg/d propylthiouracil daily for 35 d. With continued feeding of PTU steers were sequentially injected with thyroxine (T4, 5 mg/d, IM for 5 d) followed by triiodothyronine (T3, 2 mg/d, IM for 5 d). An injection of bovine pituitary growth hormone (GH, 0.1 mg/kg, IM) was given to each steer on day 35 of PTU, day 5 of T4 and again on day 5 of T3. PTU alone increased plasma thyroid stimulating hormone (TSH), decreased plasma T4 and T3 but had no influence on IGF-I. T3, but not T4, lowered plasma TSH, IGF-I and the IGF-I response to GH (P < .05). Next, twelve bull calves (av wht 167 kg) were divided equally into two groups. A control group was injected daily for five d with buffered saline; the experimental group was concurrently treated with T3 (5 mg/d, sc) for five d. Beginning the sixth day, all calves were injected with GH (0.1 mg/kg, IM daily) for three d with the respective buffer or T3 treatments continuing. Plasma IGF-I was depressed 29% by T3. The incremental area under the three-d response curve was less (P < .03) in T3 cattle. A growth trial was conducted in which twenty-four Angus x Hereford steers were injected daily with T3 (2 mg/kg, bi-daily x 56 d) or implanted with Synovex-S (S) in a 2 x 2 factorial arrangement. Synovex increased empty body protein gain (EBPG) and plasma IGF-I 15.5 and 27.9% (P < .01), respectively; T3 decreased EBPG and plasma IGF-I 13.9 and 15.1% (P < .07), respectively, in steers which maintained suppression in plasma TSH. The data support the conclusion that elevated T3 decreases plasma IGF-I, in part, through a diminished GH-responsiveness and anabolic treatments such as S can reverse the effects of excess T3.

Plasma and tissue concentrations and molecular forms of somatostatin in calves infected with Sarcocystis cruzi

The effects of parasitic infection on plasma and tissue content of immunoreactive somatostatin (SRIF) were studied in 4-mo old male calves inoculated with the protozoan Sarcocystis cruzi. Because feed intake significantly decreased (70%) in infected calves around day 28 postinfection (pi), concomitant with the asexual replication of S. cruzi and outward expression of clinical signs, the relative contributions of infection and associated reduction in nutrition on plasma SRIF were evaluated. Treatment groups were: noninfected ad libitum fed (C), infected (250,000 S. cruzi oocysts per os) ad libitum fed (I) and noninfected calves pairfed to the level of intake of each infected calf (PF). Mean plasma concentrations of SRIF (pg/ml) on day 30 pi were: C, 224 +/- 22; I, 742 +/- 150; PF, 246 +/- 31 (effect of infection P less than .05). In another study, SRIF was measured in plasma and in pancreatic, duodenal, jejunal and ileal tissue extracts from normal and S. cruzi infected calves. Plasma and tissue samples were collected on day 42 pi. Mean plasma SRIF were 2.5 times higher in infected than control calves. Plasma insulin and insulin-like growth factor 1 was lower in infected v control calves (P less than .02). Plasma glucagon was similar between groups. Duodenal (P less than .05) and jejunal (P less than .02) SRIF content was higher in infected than control calves. Chromatography of tissue extracts on Sephadex G-50 revealed that the increase in SRIF was accounted for, in part, by molecular forms larger than cyclic SRIF-14. Data suggest that peripheral SRIF is increased in calves during S. cruzi infection. The increase in SRIF is not solely related to plane of nutrition. Altered levels of gut SRIF(s) may be associated with perturbed metabolic regulation in parasitized animals through direct effects on the gut.

Hormonal and nutritional modulation of hepatic arginase activity in growing cattle

The hormonal and nutritional modulation of hepatic arginase activity (HARG) was characterized in growing cattle in two studies. In the first study, 20 steers (initial weight, 182 +/- 2 kg) were assigned in equal numbers to either Synovex-S (SYN) (ear implant), recombinant bovine somatotropin (Somavubove; SbV; 0.1 mg/kg intramuscularly daily), SYN + SbV, or nothing (control). Steers were individually fed, for 56 d, a concentrate (80% diet dry matter [DM]) and silage (20% diet DM) diet providing 20 g of crude protein (CP) and 252 kcal metabolizable energy (ME) per kg body weight0.75. On Day 57, samples of liver were obtained at slaughter and subsequently assayed for HARG by the incubation of a tissue homogenate for 2 hr with 250 mM arginine, with and without Mn2+ and heat activation, and the measurement of the resulting urea. HARG was uniformly increased by divalent cation (Mn2+) and heating. SYN had no effect on HARG, whereas SbV treatment resulted in an overall 34% decrease in HARG. Plasma urea nitrogen (PUN) was decreased by SbV but not consistently affected by SYN. In the second study, 16 steers (avg. initial weight, 284 +/- 5 kg) were initially fed a concentrate basal diet consisting of 11% CP and 1.96 Mcal ME for 21 d. Steers were then assigned to one of four dietary treatments (6.4 kg DM/hr per day) in a factorial arrangement of high and low CP (8 and 14%) and two levels of energy (1.96 and 2.67 Mcal ME/kg of diet DM) for 210 d and slaughtered. HARG and PUN were higher in steers fed 14% CP but were lower at each level of CP fed at the higher level of ME. The data suggest that hormonal repartitioning compounds and diet composition may modulate nitrogen metabolism by affecting the activity of arginase in the liver as well as by affecting the total content of arginase in association with changes in organ size.