Estradiol/progesterone implants increase food intake, reduce hyperglycemia and increase insulin resistance in endotoxic steers

C D McMahon, T H Elsasser1, D R Gunter, L G Sanders2, B P Steele and J L Sartin

Department of Anatomy, Physiology and Pharmacology, 2Discrete and Statistical Sciences, Auburn University, Auburn, Alabama 36849, USA and 1US Department of Agriculture, Agricultural Research Service, Growth Biology Laboratory, Beltsville, Maryland 20705, USA

(Requests for offprints should be addressed to J L Sartin, Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849-5520, USA)


Abstract

High doses of lipopolysaccharide (LPS) induce transient hyperglycemia, then chronic hypoglycemia and increased insulin resistance. In addition, appetite is reduced, while body temperature, concentrations of cortisol and tumor necrosis factor alpha (TNFalpha) are elevated. Furthermore, concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I) are reduced in cattle. The objectives of this study were to determine whether a gonadal steroid implant (20 mg estrogen and 200 mg progesterone) given to endotoxemic steers would: (1) reduce hyperglycemia, reduce hypoglycemia, reduce insulin resistance, (2) reduce changes concentrations of GH and IGF-I, (3) reduce inappetence, and reduce concentrations of blood urea nitrogen (BUN) and non-esterified fatty acids (NEFA), (4) reduce fever and concentrations of TNFalpha and cortisol. Holstein steers were assigned within a 2×2 factorial arrangement of treatments as follows (n=five per group): C/C, no steroid and vehicle; S/C, steroid and vehicle; C/E, no steroid and LPS (1 µg/kg BW, i.v.); S/E, steroid and endotoxin. Steroid implants were given at 20 weeks of age (d 0) and serial blood samples (15 min) were collected on d 14 for 8 h, with vehicle or LPS injected after 2 h. Intravenous glucose tolerance tests (100 mg/kg BW) were carried out at 6 h and 24 h. Hyperglycemia was 67% lower (P<0.05) in S/E- compared with C/E-treated steers between 30 and 150 min after i.v. injection of LPS. Hypoglycemia developed after 4 h and insulin resistance was greater in S/E- compared with C/E-treated steers (P<0.05) steers at 6 h and 24 h. Concentrations of IGF-I were restored earlier in steroid-treated steers than in controls. Concentrations of GH were not affected by steroids, but increased an hour after injection of LPS, then were reduced for two hours. Appetite was greater (P<0.05) in S/E- (2.1%BW) compared with C/E-treated steers (1.1%BW) (pooled s.e.m.=0.3). Concentrations of NEFA increased after injecting LPS, but concentrations were lower (P<0.05) in S/E- compared with C/E-treated steers. Lipopolysaccharide did not affect concentrations of BUN, but concentrations were lower in steroid-treated steers. Steroids did not affect body temperature, or concentrations of TNFalpha and cortisol. In summary, gonadal steroids reduce hyperglycemia, reduce inappetence and tissue wasting, but increase insulin resistance. Furthermore, concentrations of IGF-I are restored earlier in steroid-treated than in non-steroid treated steers injected with LPS. It is concluded that gonadal steroids reduce severity of some endocrine and metabolic parameters associated with endotoxemia. However, it is unlikely that gonadal steroids acted via antiinflammatory and immunosuppressive actions of glucocorticoids or through reducing concentrations of cytokines.


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Journal of Endocrinology


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