Reproduction in Domestic Animals

Reprod Dom Anim 43 (Suppl. 2), 317–323 (2008); doi: 10.1111/j.1439-0531.2008.01180.xISSN 0936-6768Comparative Aspects of the Endotoxin- and Cytokine-Induced Endocrine CascadeInfluencing Neuroendocrine Control of Growth and Reproduction in Farm AnimalsBK Whitlock 1 , JA Daniel 2 , RR Wilborn 3 , TH Elsasser 4 , JA Carroll 5 and JL Sartin 11 Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA; 2 Department ofAnimal Science, Berry College, Mt. Berry, GA, USA; 3 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn,AL, USA; 4 Growth Biology Laboratory, USDA ⁄ ARS, Beltsville, MD, USA; 5 Livestock Issues Research Unit, USDA ⁄ ARS, Lubbock, TX, USAContentsDisease in animals is a well-known inhibitor of growth andreproduction. Earlier studies were initiated to determine theeffects of endotoxin on pituitary hormone secretion. Thesestudies found that in sheep, growth hormone (GH) concentrationwas elevated, whereas insulin-like growth factor-I(IGF-I) was inhibited, as was luteinizing hormone (LH).Examination of the site of action of endotoxin in sheepdetermined that somatotropes expressed the endotoxin receptor(CD14) and that both endotoxin and interleukin-Ibactivated GH secretion directly from the pituitary. In the faceof elevated GH, there is a reduction of IGF-I in all speciesexamined. As GH cannot activate IGF-I release duringdisease, there appears to be a downregulation of GH signallingat the liver, perhaps related to altered nitration of Janus kinase(JAK). In contrast to GH downregulation, LH release isinhibited at the level of the hypothalamus. New insights havebeen gained in determining the mechanisms by which diseaseperturbs growth and reproduction, particularly with regard tonitration of critical control pathways, with this perhaps servingas a novel mechanism central to lipopolysaccharide suppressionof all signalling pathways. This pathway-based analysis iscritical to the developing novel strategies to reverse thedetrimental effect of disease on animal production.IntroductionGram-negative bacterial infections such as Escherichiacoli (E. coli), Salmonella, Pseudomonas and Proteus tendto occur frequently in farm animals. Common portals ofentry for these Gram-negative (endotoxin-containing)bacteria include, but are not limited to, the gastrointestinalsystem, the reproductive tract (especially uteri ofpostpartum animals), and the mammary gland. Infectionsof these systems or organs result in some of themost common and costly diseases of production ⁄ farmanimals such as enteritis, endometritis ⁄ metritis andmastitis. Regardless of the chronicity, infections in farmanimals with bacteria containing endotoxin, and thecytokine and endocrine changes that result, inevitablyimpact growth, metabolism and reproduction in anegative manner.Acute diarrhoea, often caused by Gram-negativebacteria such as enterotoxigenic E. coli and Salmonella,is a common disease in newborn calves and accounts formore than 50% of pre-weaning deaths in intensivelyraised calves (USDA 1996). However, pre-weaningmortality of farm animals may be just the beginning ofeconomic losses secondary to enteritis caused by Gramnegativebacteria. Other consequences of neonataldiarrhoea are as follows: (1) greater morbidity secondaryto increased susceptibility to other pathogens, (2)impaired growth rates due to reduced food intake andmetabolic disturbances and (3) delayed puberty anddecreased reproductive productivity (production ofoffspring and milk) as a result of poor growth ratesand inadequate energy stores.The outcomes of bacterial infection associated withthe postpartum uterus include puerperal metritis, clinicalendometritis, pyometra and subclinical endometritis(Sheldon et al. 2006). Arcanobacterium pyogenes(A. pyogenes), E. coli and other Gram-negative bacteria,namely Fusobacterium necrophorum (F. necrophorum)and Bacteroides spp., are predominant in the uterus ofclinically diseased animals (Hirvonen et al. 1999). Thesecommon forms of reproductive tract diseases in farmanimals (especially dairy cows) may delay the completeregeneration of endometrium, disrupt the resumption ofcyclic ovarian function resulting in postponement of thefirst insemination, increase the numbers of inseminationsper conception and thus prolong the calvinginterval and decrease the calving rate (Hussain andDaniel 1991). It is clear that uterine infections andconsequential diseases have detrimental effects onreproductive performance of dairy cows. As mostclinical and reproductive consequences are attributedto the presence of A. pyogenes in combination withorganisms like E. coli and other Gram-negative bacteria,a better understanding in pathogenesis and the mechanismsinvolved is of great practical and economicimportance.Mastitis is one of the major bacterial diseases inpostpartum farm animals, especially dairy cows. In theearly weeks of lactation, Gram-negative bacteria may bethe predominant mastitis pathogen. Clinical cases ofGram-negative mastitis load the hosts with endotoxin.In lactating cows, marked changes in plasma levels ofcertain energy-related metabolites were reported simultaneouswith the endotoxin-induced endocrine alterations.Concentrations of glucose tended to increaseinitially then subsequently declined and there was atendency for increased non-esterified fatty acid values,whereas plasma b-hydroxybutyrate (BHB) decreasedlinearly in a dose-dependent manner after lipopolysaccharide(LPS) infusion (Waldron et al. 2003).In addition to endotoxin from Gram-negative bacteriacausing metabolic perturbations, abnormal metabolicstatus of farm animals can influence their responseto infection. Epidemiological studies have demonstratedinterrelations among negative energy balance-relatedmetabolic disorders (hepatic lipidosis and ketosis), theincreased incidence of clinical mastitis and theÓ 2008 The Authors. Journal compilation Ó 2008 Blackwell Verlag