Dichotomy between Serum Free Triiodothyronine and Free Thyroxine Concentrations in Familial Thyroxine- Binding Globulin Deficiency

El-Gareib

et al. 2012

Excessive concentrations of free radicals in the developing brain may lead to neurons maldevelopment and neurons damage and death. Thyroid hormones (THs) states play an important role in affecting the modulation of oxidative stress and antioxidant defense system. Thus, the objective of this study was to clarify the effect of hypothyroidism and hyperthyroidism in rat dams on the neurons development of different brain regions of their offspring at several postnatal weeks in relation to changes in the oxidative stress and antioxidant defense system. The adult female rats were administered methimazole (MMI) in drinking water (0.02% w/v) from gestation day 1 to lactation day 21 to induce hypothyroidism and exogenous thyroxine (T4) in drinking water (0.002% w/v) beside intragastric incubation of 50--200 T4 μg/kg body weight (b. wt.) to induce hyperthyroidism. In normal female rats, the sera total thyroxine (TT4) and total triiodothyronine (TT3) levels were detectably increased at day 10 post-partum than those at day 10 of pregnancy. Free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations in normal offspring were elevated at first, second and third postnatal weeks in an age-dependent manner. In hypothyroid group, a marked depression was observed in sera of dam TT3 and TT4 as well as offspring FT3, FT4 and GH, while there was a significant increase in TSH level with the age progress. The reverse pattern to latter state was recorded in hyperthyroid group. Concomitantly, in control offspring, the rate of neuron development in both cerebellar and cerebral cortex was increased in its density and complexity with age progress. This development may depend, largely, on THs state. Both maternal hypothyroidism and hyperthyroidism caused severe growth retardation in neurons of these regions of their offspring from the first to third weeks. Additionally, in normal offspring, seven antioxidant enzymes, four non-enzymatic antioxidants and one oxidative stress marker (lipid peroxidation, LPO) followed a synchronized course of alterations in cerebrum, cerebellum and medulla oblongata. In both thyroid states, the oxidative damage has been demonstrated by the increased LPO and inhibition of enzymatic and non-enzymatic antioxidants in most examined ages and brain regions. These disturbances in the antioxidant defense system led to deterioration in the neuronal maturation and development. In conclusion, it can be suggested that the maldevelopment of neurons and dendrites in different brain regions of offspring of hypothyroid and hyperthyroid mother rat dams may be attributed, at least in part, to the excess oxidative stress and deteriorated antioxidant defense system in such conditions.

Section: Methodsmentioning

confidence: 99%

Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: II—The developmental pattern of neurons in relation to oxidative stress and antioxidant defense system

El-Gareib

et al. 2012

“…Estimation of total thyroxine (TT4), total triiodothyronine (TT3) in sera of mothers and free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) in sera of their offspring were determined in Diabetic Endocrine Metabolic Pediatric Unit, Center for Social and Preventive Medicine, New Children Hospital, Faculty of Medicine, Cairo University according to the methods of Thakur et al (1997), Maes et al (1997), Larsen (1982), Smals et al (1981), Mandel et al (1993) and Reutens (1995), respectively. The kits for these hormones were obtained from Calbiotech INC (CBI), USA.…”

Section: Methodsmentioning

confidence: 99%

Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: I. The development of the thyroid hormones–neurotransmitters and adenosinergic system interactions

El-Tawab

2010

123

The adequate functioning of the maternal thyroid gland plays an important role to ensure that the offspring develop normally. Thus, maternal hypo- and hyperthyroidism are used from the gestation day 1 to lactation day 21, in general, to recognize the alleged association of offspring abnormalities associated with the different thyroid status. In maternal rats during pregnancy and lactation, hypothyroidism in one group was performed by antithyroid drug, methimazole (MMI) that was added in drinking water at concentration 0.02% and hyperthyroidism in the other group was induced by exogenous thyroxine (T4) (from 50 microg to 200 microg/kg body weight) intragastric administration beside adding 0.002% T4 to the drinking water. The hypothyroid and hyperthyroid states in mothers during pregnancy and lactation periods were confirmed by measuring total thyroxine (TT4) and triiodothyronine (TT3) at gestational day 10 and 10 days post-partum, respectively; the effect was more pronounced at the later period than the first. In offspring of control maternal rats, the free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations were pronouncedly increased as the age progressed from 1 to 3 weeks. In hypothyroid group, a marked decrease in serum FT3, FT4 and GH levels was observed while there was a significant increase in TSH level with age progress as compared with the corresponding control. The reverse pattern to latter state was recorded in hyperthyroid group. The thyroid gland of offspring of hypothyroid group, exhibited some histopathological changes as luminal obliteration of follicles, hyperplasia, fibroblastic proliferation and some degenerative changes throughout the experimental period. The offspring of hyperthyroid rats showed larger and less thyroid follicles with flattened cell lining epithelium, decreased thyroid gland size and some degenerative changes along the experimental period. On the other hand, the biochemical data revealed that in control offspring, the levels of iodothyronine 5'-monodeiodinase (5'-DI), monoamines, gamma-aminobutyric acid (GABA), acetylcholinesterase (AchE), ATPase-enzymes (Na(+),K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) follow a synchronized course of development in all investigated brain regions (cerebrum, cerebellum and medulla oblongata). In addition, the depression in 5'-DI activity, monoamines levels with age progress in all investigated regions, was more pronounced in hypothyroid offspring, while they were increased significantly in hyperthyroid ones in comparison with their respective controls. Conversely, the reverse pattern was recorded in level of the inhibitory transmitter, GABA while there was a disturbance in AchE and ATPases activities in both treated groups along the experimental period in all studied regions. In conclusion, the hypothyroid status during pregnancy and lactation produced inhibitory effects on monoamines, AchE and ATPases and excitatory actions on GABA in different brain regions of the offspring while the hypert...

“…Estimation of total thyroxine (TT4), total triiodothyronine (TT3) in sera of mothers and free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) in sera of their newborns were determined in Diabetic Endocrine Metabolic Pediatric Unit, Center for Social and Preventive Medicine, New Children Hospital, Faculty of Medicine, Cairo University according to the methods of Thakur et al (1997), Maes et al (1997), Larsen (1982), Smals et al (1981), Mandel et al (1993) and Reutens (1995), respectively. The kits for these hormones were obtained from Calbiotech INC (CBI), USA.…”

Section: Methodsmentioning

confidence: 99%

Comparative study of the effects of experimentally induced hypothyroidism and hyperthyroidism in some brain regions in albino rats

El-Bakry

El-Gareib

2010

Thyroid hormones (THs) play a crucial role in the development and physiological functioning of different body organs especially the brain. Therefore, the objective of this study was to show the histopathological effects of the different thyroid states on some brain regions (cerebrum and cerebellum) and the skeletal features of their newborns during the postnatal development from the 1st to 3rd week. The female white albino rats were allocated into 3 groups as follows: the experimental hypothyroidism group is induced by 0.02% methimazole (MMI) (w/v) in drinking water, while the experimental hyperthyroidism group is performed by exogenous T4 [from 50 to 200microg/kg body weight intragastric administration beside adding 0.002% T4 (w/v) to the drinking water] from the gestation day 1 to lactation day 21 and control group which received tap water. As well, both maternal hypo- and hyperthyroidism caused some malformation and developmental defects in the cerebellar and cerebral cortex of their newborns along the duration of the experiment. These degenerative symptoms became more prominent and widely spread at the 3rd postnatal week. Concomitantly, there were some degeneration, deformation and severe growth retardation in neurons of these regions in both treated groups throughout the experimental period. Moreover, the skeletal features of these newborns were accelerated in hyperthyroid group while these maturations were delayed partially in hypothyroid ones during the examined periods. These alterations, on both treated groups, were age and dose dependent. Thus, further studies need to be done to emphasize this concept.