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Lars Holzhausen

“Influence of the Insulin-like Growth Factor system on the endocrinological answer after an experimentally induced inflammation of the uterus”

Dairy cattle with low Insulin-like Growth Factor I (IGF-I) concentrations four to six weeks before parturition show a higher incidence of production diseases in com-parison to animals with high IGF-I levels at this time. The Growth Hormone (GH)-IGF-I axis interacts with the immune system and other endocrine axes.

This present work analysed the influence of different IGF-I concentrations of cattle between the days 240 to 254 post inseminationem (p. insem.) on the endocrine systems during late pregnancy. Furthermore, endocrine changes after an intrauterine inflammatory insult after parturition were investigated.

Blood samples were taken from healthy pluriparous Holstein Friesian cows between days 240 and 254 p. insem. to determine peripheral IGF-I concentrations. Ten animals with high (>175 ng/ml) and ten with low (<125 ng/ml) IGF-I concentrations were selected for further studies. The cows were transported to the Clinic for Cattle before day 266 p. insem. One IGF-I low animal was excluded from the experiment before day 266 due to severe aggressiveness. Blood samples were taken daily from the remaining ten IGF-I high and nine IGF-I low animals until birth occurred spon-taneously.

For a postpartal inflammatory challenge the following essential factors were defined:

clinical healthiness until birth, a physiological parturition, and an expulsion of the placenta within 12 hours after birth. Thirty minutes after the release of the placenta an intrauterine infusion was performed with 1000 ml Lipopolysaccharide (LPS) solution (E. coli O55:B5, Sigma Aldrich, St. Louis, Missouri, USA, concentration 5 µg/ml, IGF-I high and IGF-I low cows each n = 6). Cows, which did not fulfill the present criteria, were used as a control group (n = 7). Endocrine parameters were examined without an iatrogenic inflammatory insult (12 h p.p.; 1000 ml physiological sodium chloride solution intrauterine).

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A swap sample was taken from every cow 10 minutes before the infusion and examined for microbiological contamination. Furthermore, a blood sample from the vena jugularis was withdrawn before and six times after the infusion in 30 minutes intervals. After 180 minutes the LPS group was sacrificed and tissue samples were taken from uterus, liver, muscle, and fat.

The parameters IGF-I, GH, Cortisol, Prostaglandin F metabolite, Trijodthyronin, thyroxin (T4), Insulin, Non-Esterified Fatty Acids (NEFA), and Adrenocorticotropic hormone were determined in blood. The tissue samples were examined for the expression of the GH receptor. The liver was additionally semi-quantitatively analyzed for the expression amount of the GH receptor.

Until day 275 p. insem. the IGF-I concentrations between the groups were different (P < 0.05). The IGF-I concentration of the IGF-I high group showed a more distinct decline compared to the IGF-I low group (P < 0.05). In contrast the GH concen-trations remained constant in both groups of animals (P > 0.05). Furthermore, during the time period before parturition the IGF-I low group showed lower T4 concentrations as well as higher cortisol and higher NEFA concentrations than the IGF-I high group (P < 0.05).

Immediately before the LPS infusion the swap samples of the IGF-I low animals contained significantly more Clostridium species compared to the IGF-I high animals.

The intrauterine infusion of LPS led to a decline of T4 in the six IGF-I low cows and to rise of T4 in the six IGF-I high animals (P < 0.05). Cortisol concentrations of the IGF-I low animals were higher (P < 0.05) compared to the IGF-I high group and after 150 minutes an increase (P < 0.05) could be noticed only in the IGF-I low group. There were no histological differences (P ≥ 0.05) between the two IGF-I groups. The GH receptor was detectable via immune histology in all examined tissues. A difference in the expression amount of the liver was not seen.

The results of this work show differences in the endocrine constellation and the reaction on an inflammatory insult in the uterus between the IGF-I groups. This might correlate to a higher risk of production diseases in the IGF-I low group out of other publications. This endocrine differences could influence immune cells differently.

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