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C. Aceves, A. Ruiz-J., C. Romero and C. Valverde-R.

Abstract. Serum levels of thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) were studied in dry, early (first trimester) and middle (second trimester) lactating purebred Holstein cows. The study encompassed three different seasons: autumn, winter and spring. Under comfortable weather conditions (temperature 22°C; relative humidity, 40%) or moderately hot (28°C; 60%), January and October, respectively, cows in early lactation exhibited significantly lower levels of T4 and T3, and higher values of rT3 than dry or middle lactating animals. In contrast, during May, when environmental temperature increased (34°C; 40%), a clear-cut shift in T3/rT3ratio occurred, and animals in early lactation exhibited the highest T3 and the lowest rT3 concentrations.

These findings suggest that in dairy cattle, peripheral thyroid hormone metabolism plays a major role in regulating the homeorhetic responses involved in the maintenance of high priority functions.

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C. Aceves, C. Romero, L. Sahagun and C. Valverde-R

Abstract. Milk yields and the circulating profile of T4, T3 and rT3 were assessed during three different seasons of the year, in first trimester lactating (L) and in dry (D) multiparous holstein cows acclimated to distinct weather conditions. Within the thermoneutral zone (18–28°C; 40–60% RH) and regardless of their geographical location, the thyroid hormone profile in all L-cows (n = 50) resembled the so-called euthyroid sick syndrome (T4, 43.7 ± 7.7 nmol/l; T3, 1.31 ± 0.10 nmol/l and rT3, 0.52 ± 0.08 nmol/l). In both groups of animals the T3/T4 molar ratio was similar within the entire range of climates encompassed in the study. However, both groups exhibited a significant shift in the T3/rt3 molar ratio during cold (10°C; 50%) or hot-dry (34°C; 40%) weather conditions. This shift reaches maximum values (L, 6.5 ± 1.2; D, 7.9 ± 1.0 nmoles/l) under hot-humid conditions (28–42°C; 60–90%). The relative increase of T3 levels from comfortable to cold or hot environmental temperatures, was significantly higher in L than D animals (30 vs 12%, respectively). Furthermore, only L-cows exhibited a significant decrease in the rT3/T4 molar ratio during either type of thermoregulatory demands, as well as a significant increase of T4 values under heat-acclimation. These results suggest that heat-acclimation in dairy cattle does not depress thyroid gland activity, and lend further support to the notion that adaptive thermoregulatory mechanisms in homeothermic vertebrates, involve adjustments in the peripheral monodeiodinative pathways of thyroid hormones.

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MA Rol De Lama, A Perez-Romero, JA Tresguerres, M Hermanussen and C Ariznavarreta

OBJECTIVE: A novel non-invasive technique termed microknemometry, which allows daily leg length measurement, was used to investigate the growth promoting effect of growth hormone (GH) on peripubertal rats. We compared the effect of different patterns of recombinant human (rh) GH administration to peripubertal male rats with the effect produced by two daily administrations of the same amount of rhGH to peripubertal female rats or adult male rats. Another group of peripubertal male rats was also submitted to a 3-day period of starvation, in order to study catch-up growth during refeeding and to determine whether this process could be stimulated by exogenous GH administration. RESULTS: GH treatment was unable to stimulate tibial growth or weight gain in peripubertal males, whereas a clear growth promoting effect was observed in female rats and also in adult male rats. Starvation caused a dramatic body weight loss, and a reduction in tibial growth rate. Peripubertal male rats gained body weight faster than unstarved animals during refeeding, although recovery was not complete after nine days. Tibial growth, however, was resumed at the same speed as in normally fed males. This means that no catch-up effect was observed after refeeding in animals either with or without GH treatment. CONCLUSIONS: During peripuberty, normal male rats grow at a maximal speed that cannot be further increased by exogenous GH treatment, whereas age-matched female rats or older males grow at a slower rate than peripubertal males. Thus, exogenous rhGH administration is capable of enhancing growth velocity.

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Darya Gorbenko Del Blanco, Christopher J Romero, Daniel Diaczok, Laura C G de Graaff, Sally Radovick and Anita C S Hokken-Koelega

Orthodenticle homolog 2 (OTX2) is a homeobox family transcription factor required for brain and eye formation. Various genetic alterations in OTX2 have been described, mostly in patients with severe ocular malformations. In order to expand the knowledge of the spectrum of OTX2 mutation, we performed OTX2 mutation screening in 92 patients with combined pituitary hormone deficiency (CPHD). We directly sequenced the coding regions and exon–intron boundaries of OTX2 in 92 CPHD patients from the Dutch HYPOPIT study in whom mutations in the classical CPHD genes PROP1, POU1F1, HESX1, LHX3, and LHX4 had been ruled out. Among 92 CPHD patients, we identified a novel heterozygous missense mutation c.401C>G (p.Pro134Arg) in a patient with CPHD, pituitary malformation, and an underdeveloped left optic nerve. Binding of both the wild-type and mutant OTX2 proteins to bicoid binding sites was equivalent; however, the mutant OTX2 exhibited decreased transactivation. We describe a novel missense heterozygous OTX2 mutation that acts as a dominant negative inhibitor of target gene expression in a patient with CPHD, pituitary malformation, and optic nerve hypoplasia. We provide an overview of all OTX2 mutations described till date, which show that OTX2 is a promising candidate gene for genetic screening of patients with CPHD or isolated GH deficiency (IGHD). As the majority of the OTX2 mutations found in patients with CPHD, IGHD, or short stature have been found in exon 5, we recommend starting mutational screening in those patients in exon 5 of the gene.

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Carlos Posadas-Romero, Esteban Jorge-Galarza, Rosalinda Posadas-Sánchez, Jorge Acuña-Valerio, Juan G Juárez-Rojas, Eric Kimura-Hayama, Aida Medina-Urrutia and Guillermo C Cardoso-Saldaña

Background

The association of subclinical hypothyroidism (SCH) with insulin resistance, metabolic syndrome (MS), and coronary atherosclerosis is uncertain.

Objective

To investigate the role of increased intrahepatic fat in the association of SCH with insulin resistance, MS, and coronary atherosclerosis.

Design, patients, and methods

We conducted a cross-sectional study in a sample of 753 subjects (46% males) aged 35–70 years with no history of diabetes, renal, hepatic, thyroid, or coronary heart disease, and were participants of the Genetics of Atherosclerotic Disease study. SCH was defined as a high serum TSH level with normal free thyroxine concentration. Fatty liver (FL), coronary artery calcification (CAC), and abdominal visceral adipose tissue were assessed by computed tomography. Cross-sectional associations of SCH with and without FL, with MS, insulin resistance, and subclinical atherosclerosis defined as a CAC score >0, were examined in logistic regression models.

Results

SCH was observed in 17.7% of the population studied. The prevalence of FL was similar in both euthyroid and SCH subjects (31.8 vs 27.8%, P=0.371). SCH plus FL subjects were heavier and had more metabolic abnormalities compared with SCH plus normal liver subjects. In multivariate-adjusted logistic regression analyses, SCH plus FL was associated with MS (odds ratio (OR): 2.73, 95% CI: 1.26–5.92), insulin resistance (OR: 4.91, 95% CI: 1.63–14.75), and CAC score >0 (OR: 3.05, 95% CI: 1.20–7.76). SCH without FL showed no associations.

Conclusion

SCH with FL is associated with increased odds of MS, insulin resistance, and CAC, independent of potential confounders.