Effects Of Neonatal Hyperthyroidism Research Articles

Effect of neonatal hyperthyroidism on GH gene expression reprogramming and physiological repercussions in rat adulthood

The neonatal period (NP) is a critical phase of the development in which the expression pattern of most genes is established. Thyroid hormones (TH) play a key role in this process and, alterations in its availability in the NP may lead to different patterns of gene expression, which might reflect in the permanent expression of several genes in the adulthood. GH gene expression in the pituitary is greatly dependent on TH in the early postnatal life; thus, modifications of thyroid state in NP might lead to alterations in GH gene expression as well as to physiological repercussions in the adult life. This study aimed to investigate this possibility by means of the induction of a neonatal hyperthyroidism in rats (4 mug of 3,5,3'-triiodo-l-thyronine (T3)/100 g body weight, s.c.) for 5, 15 or 30 days, and further evaluation of GH gene expression, as well as its physiological consequences in adult rats subjected to a transient hyperthyroidism in the first 30 days of life. GH mRNA level was shown to be increased in T3-treated rats for 5 days; when the treatment was extended to 15 or 30 days, the GH mRNA levels were similar to the control group. Moreover, rats treated with T3 for 30 days and killed when 90 days old, i.e., 60 days at the end of the T3 treatment, showed decreased GH mRNA content, body weight, bone mineral density, and lean body mass. (1) T3 effects on GH gene expression depend on the period of life in which the hyperthyroidism is set and on the length of T3 treatment in the NP and (2) transient neonatal hyperthyroidism leads to a lower GH mRNA expression in adult life accompanied by physiological repercussions indicative of GH deficiency.

Neonatal hyperthyroidism causes impairment in submandibular gland-nerve growth factor (SMG-NGF) ontogeny in mice.

The effect of neonatal hyperthyroidism on submandibular gland (SMG) nerve growth factor (NGF) concentrations was studied in female Swiss-Webster mice. For this purpose, newborn female pups were treated with thyroxine (T4, 0.4 microgram/g body weight/day) from birth through day 6, while their littermate pups were treated with similar volumes of vehicle. Animals were sacrificed on days 7, 15, 21, 31 and 71. Somatic growth (body weight and nose to rump length), serum T4 and T3 concentrations, and SMG and serum-NGF concentrations were measured. The data indicate that neonatal hyperthyroidism a) causes inhibition of somatic growth; b) induces alterations in normal ontogenic patterns of serum T4 and T3; c) impairs the developmental rise in SMG-NGF concentration and d) transiently increases serum-NGF levels.

Effect of neonatal hyperthyroidism upon the regulation of TSH secretion in rats.

The neo-T4 syndrome was induced in rats by administration of 30 micrograms T4/in 5 doses starting on the first day of life. In the first experiment (A), neo-T4 and saline-control rats were divided into two populations, one of which was thyroidectomized on day 25. All rats then received 5 micrograms T4/100 g b.w. on days 42, 43 and 44, and were sacrificed on day 45. In the second experiment (B), neo-T4 and saline-control rats were thyroidectomized at 25 days of age and were sacrificed 10, 20 and 40 days after the operation. In both experiments, pituitary and plasma TSH and pituitary GH were determined. T4 administration has the same effect on plasma and pituitary TSH regulation in neo-T4 and control rats, thyroidectomized or not. The increase in pituitary GH produced by T4 is smaller in the thyroidectomized neo-T4 animals. The comparison between T4-induced increases of pituitary TSH in thyroidectomized neo-T4 and saline control-rats, and the corresponding decreases in non-thyroidectomized animals suggests an alteration in TSH synthesis which has previously been compared with that found in rats with lesions of the hypothalamus. However, the changes in pituitary and plasma TSH levels in neo-T4 rats at different intervals after thyroidectomy do not coincide with those described for rats with hypothalamic lesions. The possible perturbation in pituitary TSH synthesis proposed for neo-T4 rats accords with the lack of response to TRH found in adult animals treated with thyroxine, an effect which remains even when plasma T4 levels decrease.

Neonatal hyperthyroidism: effects on sympathetic responses to stress in adult rats.

Treatment of developing rats with thyroid hormone results in accelerated maturation of sympathetic and adrenal medullary responses to reflex activation of central sympathetic outflow. In this study, we examined the effects of neonatal hyperthyroidism on the responsiveness of the sympathetic nervous system of adult rats to acute stress. Hyperthyroidism was produced in Long-Evans hooded rats by injections of thyroxine (neo-T4, 1 mg/kg body wt) on postnatal days 1-4. Littermate controls received injections of vehicle only. In adulthood, male rats of the two groups were prepared with chronic tail artery catheters to allow repeated sampling of blood and direct measurements of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats/min). Two days after surgery, rats were stressed by exposure to 1 min of inescapable foot shock (2.0 mA, 0.6-s duration, every 6 s). The activity of the sympathetic nervous system was assessed by measuring plasma levels of norepinephrine (NE) and epinephrine (E). Basal plasma levels of NE and E and resting MAP did not differ between neo-T4 and control rats. However, basal HR was elevated in neo-T4 rats. Footshock-induced increments in plasma levels of both catecholamines were greater in neo-T4 compared with control rats even though behavioral responses to footshock were similar across groups. However, neo-T4 rats were more active when tested in an open field on each of 3 consecutive days. These findings indicate that neonatal treatment with T4 results in hyperresponsiveness of the sympathoadrenal medullary system to acute stress that persists into adulthood.

Thyroid Hormone and Cell Formation in the Developing Rat Cerebellum

Effects of neonatal hyperthyroidism on cell formation in the developing rat cerebellum were reinvestigated. Administration at birth of excessive doses of thyroxine or triiodothyronine led to an early stimulation of cell acquisition, followed by a permanent deficit of cells in the cerebellum. The corrective effects of physiological doses of thyroxine on the troubles of the histological and biochemical development of the cerebellum in thyroid-deficient animals were also studied. As early as 6 days, cell maturation and formation were already retarded in animals treated with propylthiouracil, but, as previously reported, cell formation was prolonged and the final number of cells was normal. Administration to thyroid-deficient animals of progressively increasing doses of thyroxine, nearly equal to the amounts of hormone secreted by the thyroid gland of the developing normal rat, returned the evolution of the cerebellar wet weight and of the cerebellar DNA to normal, as well as the histological maturation of the cerebellum, even if it did not entirely correct the retardation of body growth. These results are consistent with the view that thyroid hormone early stimulates maturation of the cerebellar germinative cells and subsequently interacts with cell formation in the cerebellum, and that this action is physiological.

Effect of neonatal hyperthyroidism on maturation and learning in the rat

1. 1. Rats made hyperthyroid by injections of l-triiodothyronine (T3) given during the first 24 days of life grew more slowly but matured more rapidly than normal litter-mates. The eyes opened earlier and the age at which the righting and placing reactions first appeared was accelerated. The effects of combining growth hormones with T3 were almost identical with those of giving T3 alone; those of giving T3 alone over the 2nd to 4th days of life were similar in trend but, except in the case of eye opening, did not attain statistical significance. 2. 2. Despite this accelerated maturation the animals given all three treatments performed significantly less well, when adult, on the Hebb-Williams closed field test. 3. 3. Maturation of innately organized behaviour was not advanced in animals in which treatment was delayed until the 14th day and the performance of these rats on the closed field test was equal to that of the controls. 4. 4. These findings are discussed in the light of growth and endocrine changes reported elsewhere.