Effect of Thyromimetic GC-1 Selective Signaling on Reproductive and Lactational Performance in the Hypothyroid Rat

<b><i>Introduction:</i></b> The potential of the thyroid hormone receptor β (TRβ1) selective analog GC-1 has been widely proven in animal models and humans. However, its effect on the reproductive stage of the female rat has not been evaluated. <b><i>Methods:</i></b> The effect of the administration of GC-1 or equimolar doses of triiodothyronine (T3) was evaluated on the reproductive performance of the hypothyroid female rat and the indirect effect on pup thyroid status, weight, and survival. <b><i>Results:</i></b> Hypothyroidism reduced the number of embryos implanted in the uterus, whereas T3 and GC-1 treatment in hypothyroid females reestablished the number of implanted embryos to normal. Initiation of labor was delayed by hypothyroidism, and T3 replacement treatment reinstated the normal timing of parturition. The administration of GC-1 alone to the lactating mother did not affect pup survival, weight, or thyroidal status. <b><i>Conclusions:</i></b> Our findings show the differential effect of thyroid hormone selective signaling during gestation and the indirect exposure of the pups; we also emphasize the plausible use of GC-1 for treatment of hypothyroid mothers during the lactation period.

Thyroid Hormone Regulation and Insulin Resistance: Insights From Animals Naturally Adapted to Fasting

The contribution of thyroidal status in insulin signaling and glucose homeostasis has been implicated as a potential pathophysiological factor in humans, but the specific mechanisms remain largely elusive. Fasting induces changes in both thyroid hormone secretion and insulin signaling. Here, we explore how mammals that undergo natural, prolonged bouts of fasting provide unique insight into evolved physiological adaptations that allow them to tolerate such conditions despite intermittent states of reversible insulin resistance. Such insights from nature may provide clues to better understand the basis of thyroidal involvement in insulin dysregulation in humans.

Bone Maturity and Thyroidal Status at Birth: Role of the Ultrasonographic Evaluation of the Distal Femoral Epiphysis

Purpose: Thyroidal hormones are important for bone development, and ultrasonographic (US) evaluation of the distal femoral epiphysis (DFE) has recently been suggested as a new method for the assessment of skeletal maturity in infants. A delayed bone maturation, expressed by a smaller or absent DFE nucleus (in terms of DFE surface area, sum of the epiphyseal diameters, or DFE height and acetabular size), has been largely demonstrated in diagnosed hypothyroid infants, while no data analyze the role and meaning of the DFE dimensions (in terms of volume) in newborn before knowledge of the congenital neonatal screening results. The aims of the present study were to ultrasonographically evaluate the volume of DFE in newborns, and to determine whether it has any predictive role for the thyroidal status at birth. Materials and Methods: 238 newborns (M/F: 121 /117) were evaluated. The gestational age, body weight and length at birth were registered. Neonatal screening for congenital hypothyroidism (CH), based on TSH levels on blood spot, was performed in all on the 3 rd day of life. The DFE volume was ultrasonographically evaluated, taking into account the three diameters of the DFE nucleus, within 48 hours of birth. Results: No newborn was found to have CH on neonatal screening. The DFE volume ranged between 0.00 cm and 0.61 cm (mean 0.14 ± 0.10 cm, median 0.13 cm). The DFE volume did not differ between males and females, while it was significantly greater in at term babies than in preterm babies. No differences in TSH values at screening were noted among the groups. The DFE volume was significantly related to gestational age, birth weight and length. A significant relationship was found between the DFE volume and TSH concentrations at screening. Conclusion: US evaluation of DFE volume provides a simple method for assessing bone maturity at birth, which is related to gestational age, body weight and length at birth. Nonetheless, it has any predictive role for thyroidal status at birth, being not related to TSH levels on neonatal screening for CH.

Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations

Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T4) and triiodothyronine (T3), and brain T3 levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T3 by 48%, serum total T4 by 21%, and whole-brain T3 by 10% at P12. Fe deficiency reduced serum total T3 by 43%, serum total T4 by 67%, and whole-brain T3 by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that at least some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels.

The influence of certain medicinal products on the function of the hypothalamo-pituitary-thyroid axis and the efficiency of substitution therapy with thyroid hormones

The influence of various medicinal preparations on the function of the hypothalamo-pituitary-thyroid axis is discussed. Thyroidal status at different somatic diseases is considered alongside the efficiency of substitution therapy with thyroid hormones for the management of hypothyroidism.