W. Bruce Currie

Adiponectin deficit during the precarious glucose economy of early lactation in dairy cows.

In rodents and primates, insulin resistance develops during pregnancy and fades after parturition. In contrast, dairy cows and other ruminants maintain insulin resistance in early lactation (EL). This adaptation favors mammary glucose uptake, an insulin-independent process, at a time when the glucose supply is scarce. Reduction in circulating levels of the insulin-sensitizing hormone adiponectin promotes insulin resistance in other species, but whether it contributes to insulin resistance in EL dairy cows is unknown. To address this question, plasma adiponectin was measured in high-yielding dairy cows during the transition from late pregnancy (LP) to EL. Plasma adiponectin varied in quadratic fashion with the highest levels in LP, a maximal reduction of 45% on the day after parturition and a progressive return to LP values over the next 8 wk. Adiponectin circulated nearly exclusively in high molecular weight complexes in LP, and this distribution remained unaffected in EL. The reduction of plasma adiponectin in EL occurred without changes in adiponectin mRNA in adipose tissue but was associated with repression of the expression of proteins associated with the endoplasmic reticulum and involved in assembly of adiponectin oligomers. Finally, EL increased the expression of the adiponectin receptor 1 in muscle and adiponectin receptor 2 in liver but had no effect on the expression of these receptors in adipose tissue and in the mammary gland. These data suggest that reduced plasma adiponectin belongs to the subset of hormonal adaptations in EL dairy cows facilitating mammary glucose uptake via promotion of insulin resistance.

Toxicologic studies with pregnant goats fed grass-legume silage grown on municipal sludge-amended subsoil

Pregnant goats were fed grass-legume silage grown on soil amended with 112 dry metric tons per hectare of municipal sewage sludge from Syracuse, New York for 135 days. Whereas PCBs were not detectable in control or sludge-grown silage, cadmium was much higher (3.81 ppm) in the sludge-grown silage as compared to the control silage (0.14 ppm). There were no consistent differences in residues of cadmium in the goats milk or body tissues of the kids when compared to controls. The concentration of cadmium in the livers of the adult animals was significantly higher (p < 0.05) in the sludge treatment than controls. No significant treatment effects were observed in mutagenic responses for the goats milk. Interestingly, the pregnant goats fed the sludge-grown silage produced far too little milk for their kids while the control animals produced sufficient milk. There were no observable changes in the tissue ultrastructure as examined by electron microscopy for both the adults and the kids from either ration treatment.

Uterine excitability and distensibility influenced by treatment in vitro with progesterone

Abstract Myometrial strips excised from rabbits at day 25 or 26 of pregnancy develop the same level of active isometric tension as those obtained at parturition when tetanized under optimal conditions in Ca++-replete medium. When Ca++ is selectively removed from the medium, active tension decays and the rate of this uncoupling reflects the progestational state of the myometrium. Strips from pregnancy which are under the influence of progesterone display a resistance to uncoupling relative to the rapid rate of uncoupling of the uterine strips obtained at term. It has been proposed that the progesterone-influenced uterus possesses a pool of Ca++-binding sites in the sarcolemma and that this reserve of Ca++ protects the strip from the uncoupling effects of removing the ion from the bathing medium. This expression of the action of the steroid can be predictably altered by incubating uterine strips in culture medium with or without added progesterone. In the absence of added steroid, the strips metabolize the endogenous progesterone and the rate of uncoupling is accelerated over the course of a few hours. Resistance to uncoupling is maintained by near physiological concentrations of progesterone in the medium. The effect of incubation without added progesterone can subsequently be reversed by delayed exposure to the steroid. The reversal process displays a 2–4 hour latency but is complete by 6 hours. This action of progesterone can be mimicked by exposure of the strips to cycloheximide or actinomycin D. The rapidity of action of these agents in establishing high resistance to uncoupling is cycloheximide > actinomycin D > progesterone. Progesterone appears to maintain high resistance to uncoupling by a tonic inhibition of transcriptional events that would otherwise lead to the sarcolemmal changes normally associated with the inhibition of labor. Steroid treatments imposed in vitro also alter resting length-tension relationships in myometrial strips. During mid to late pregnancy, the strips are very distensible and contrast with the relatively indistensible strip collected at parturition. Strips obtained during days 21 – 29 of pregnancy then incubated without progesterone acquire the indistensible properties of strips taken at parturition. Exposure to progesterone in vitro maintains distensibility but this action is progressively overcome in a dose-related fashion by incubation with bacterial collagenase. These findings indicate that changes in the organization of the collagen in the uterine strips markedly affect distensibility and suggest that progesterone may act to inhibit collagenolysis. Distensibility can be maintained by exposure to porcine relaxin in vitro , despite the absence of progesterone. The results suggest that hormonally-controlled changes in the myometrial connective tissue may contribute to the characteristic changes in the properties of the uterus attending the initiation of labor.