Thyroid hormone profiles and TSH evaluation during early pregnancy and the transition period in dairy cows.

The thyroid hormone axis is one important endocrine system within a complex system of various factors and hormones necessary to establish and maintain pregnancy in cattle and in metabolic adaptations towards lactation. Pregnancy and lactation occur contemporaneously in dairy cows, and have major impacts on thyroid hormones as well as status of the hypothalamus-pituitary thyroid axis influences pregnancy and lactation. As especially the thyroid hormone axis with special focus to TSH is not well studies in the past, the aim of the study was to examine the thyroid hormone axis, especially in heifers during adaptation to the first lactation, to verify the association between lactation and thyroid hormones. Secondly, the early pregnancy period was the focus of the present investigation. To determine thyroid hormone patterns and especially thyroid-stimulating hormone (TSH) during the transition period, 12 primiparous Holstein Friesian cows and 41 pregnant and 34 non-pregnant pluriparous cows were sampled. During the transition period, thyroxin (T4) concentrations decreased after calving in primiparous cows, and the milk yield [kg] was negatively correlated with triiodothyronine (T3) and T4 concentrations. In pregnant and non-pregnant pluriparous cows, T3, T4, TSH and free T4 (fT4) decreased between the day of ovulation (day 0) and day 18. From day 18 of gestation to day 100 after AI, an increase in TSH and fT4 and a decrease in Reverse T3 (rT3) was observed in the pregnant cows. In conclusion, the results of the present study confirm that regulative processes within the thyroid hormone metabolism occur during early lactation. For the first time it could be shown in dairy cows that TSH and fT4 increased during early pregnancy whereas rT3 decreased indicating also in bovine species a TSH stimulatory effect by pregnancy.

Number of nitrate groups determines reactivity and potency of organic nitrates: a proof of concept study in ALDH-2-/- mice.

BACKGROUND AND PURPOSE: Mitochondrial aldehyde dehydrogenase (ALDH-2) has been shown to provide a pathway for bioactivation of organic nitrates and to be prone to desensitization in response to highly potent, but not to less potent, nitrates. We therefore sought to support the hypothesis that bioactivation by ALDH-2 critically depends on the number of nitrate groups within the nitrovasodilator. EXPERIMENTAL APPROACH: Nitrates with one (PEMN), two (PEDN; GDN), three (PETriN; glyceryl trinitrate, GTN) and four (pentaerithrityl tetranitrate, PETN) nitrate groups were investigated. Vasodilatory potency was measured in isometric tension studies using isolated aortic segments of wild type (WT) and ALDH-2-/- mice. Activity of the cGMP-dependent kinase-I (reflected by levels of phosphorylated VAsodilator Stimulated Phosphoprotein, P-VASP) was quantified by Western blot analysis, mitochondrial dehydrogenase activity by HPLC. Following incubation of isolated mitochondria with PETN, PETriN-chromophore and PEDN, metabolites were quantified using chemiluminescence nitrogen detection and mass spectrometry. KEY RESULTS: Compared to WT, vasorelaxation in response to PETN, PETriN and GTN was attenuated about 10fold in ALDH-2-/- mice, identical to WT vessels preincubated with inhibitors of ALDH-2. Reduced vasodilator potency correlated with reduced P-VASP formation and diminished biotransformation of the tetranitrate- and trinitrate-compounds. None of these findings were observed for PEDN, GDN and PEMN. CONCLUSIONS AND IMPLICATIONS: Our results support the crucial role of ALDH-2 in bioactivating highly reactive nitrates like GTN, PETN and PETriN. ALDH-2-mediated relaxation by organic nitrates therefore depends mainly on the number of nitrate groups. Less potent nitrates like PEDN, GDN and PEMN are apparently biotransformed by other pathways.