Effect Of Experimental Hypothyroidism Research Articles

The effect of experimental hypothyroidism on nasal mucosa

The effect of experimental hypothyroidism on nasal mucosa

The effect of experimental hypothyroidism on the skin of adult male albino rats and the therapeutic role of topical triiodothyronine

The effect of experimental hypothyroidism on the skin of adult male albino rats and the therapeutic role of topical triiodothyronine

Effect of Experimental Hypothyroidism on Glomerular Filtration Rate and Plasma Creatinine Concentration in Dogs

Hypothyroidism affects renal function in a manner opposite the effects of hyperthyroidism. To evaluate the effects of experimentally induced hypothyroidism on glomerular filtration rate (GFR) and basal plasma creatinine concentration in dogs. Sixteen anestrous, female dogs. Hypothyroidism was induced by administration of (131)I in 8 dogs, and 8 healthy euthyroid dogs acted as controls. Exogenous plasma creatinine clearance (an estimate of GFR) was measured in all dogs before (control period) and 43-50 weeks after induction of hypothyroidism (posttreatment period). Other pharmacokinetic parameters of creatinine were also determined. No significant difference was observed for basal plasma creatinine concentration and creatinine clearance between control and hypothyroid dogs in the control period. In the posttreatment period, mean + or - SD creatinine clearance in the hypothyroid group (2.13 + or - 0.48 mL/min/kg) was lower (P < .001) than that of the control group (3.20 + or - 0.42 mL/kg/min). Nevertheless, basal plasma creatinine concentrations were not significantly different between the hypothyroid and control groups (0.74 + or - 0.18 versus 0.70 + or - 0.08 mg/dL, respectively) because endogenous production of creatinine was decreased in hypothyroid dogs (22 + or - 3 versus 32 + or - 5 mg/kg/d, P=.001). Hypothyroidism causes a substantial decrease in GFR without altering plasma creatinine concentrations, indicating that GFR evaluation is needed to identify renal dysfunction in such patients.

Cardiac angiotensin receptor expression in hypothyroidism: back to fetal gene programme?

Cardiac angiotensin receptor expression in hypothyroidism: back to fetal gene programme?

The Effects of Experimental Hypothyroidism on Hemorheology and Plasma Fibrinogen Concentration

Effects of hypothyroid on hemorheology of patients had widely attracted the attention of researchers during last decade. The present study has been planned with the purpose to determine the effects of experimental hypothyroidism on hemorheological parameters and fibrinogen concentration. To induce experimental hypothyroid methimazole (75 mg/100 g) was added to the fodder of an experimental group rats for 20 d. After experimental duration, plasma and blood viscosity, hematocrit (Hct), hemoglobin, erythrocyte rigidity index, and plasma fibrinogen concentration values of both the control and the experimental group animals were determined and evaluated. The serum T3 and T4 levels of the experimental group were found lower (p < 0.001) but TSH level higher (p < 0.001) than that of the control group. Plasma viscosity and fibrinogen concentration of hypothyroid group were found significantly higher than controls (p < 0.01). Hematocrit and hemoglobin values were also found lower in the experimental group than the control group animals (p < 0.01). However, there was no significant difference found in blood viscosity at the original Hct value but there was a significant increase at standard Hct value (p < 0.01). There was also no change in erythrocyte rigidity index between control and experimental groups. According to these results it may be said that in hypothyroidism, increased fibrinogen concentration may alter the rheological structure of blood by inducing increase in plasma viscosity.

Effects of experimental hypothyroidism on myelin sheath structural organization.

A previous study using the 2'3'cyclic nucleotide 3'phosphodiesterase (CNPase), an oligodendroglial marker that also stain ensheathed fibers, showed a decrease in the number of immunoreactive fibers and a change in the pattern of CNPase immunoreactivity (CNPase+) in hypothyroid animals. CNPase+ fibers, in mature hypothyroid animals, showed a continuous pattern of staining in contrast with a discontinuous one in controls. As CNPase, in adult animals, can be found only in regions in which oligodendrocyte cytoplasm remains as internal, external and paranodal loops, it was suggested that the reduction of thyroid hormone levels leads to a failure in myelin compaction. Previous data showed a higher frequency of some abnormalities in myelin sheath as multiple cytoplasmic loops and redundant myelin profiles in mutant animals that present a failure in myelin compaction. The increase in the frequency of these abnormalities (multiple internal and external loops and redundant myelin) indicates a failure in the interrelations between the axons and the oligodendroglial processes. To verify if the thyroid hormone deficiency during CNS development disturbs these interrelations, we evaluated the frequency of the morphological abnormalities (multiple internal and external loops and redundant myelin) in myelin sheath of corpus callosum (cc) in experimental hypothyroidism. Randomic fields were kept by electron microscopy and the analysis of the frequency of morphological abnormalities showed a significant difference in hypothyroid animals at 60-day-old (PND60), with no significant differences at 90-day-old (PND90) animals. The frequency of multiple internal loops is higher in hypothyroid animals at PND60 that indicates a disturbance in the wrapping by the oligodendroglial process. These findings showed that thyroid hormone might modulate the axon-oligodendroglial relationships that are important for the adequate temporal sequence of events that occur during myelinogenesis, with possible consequences on myelin compaction.

Effects of experimental hypothyroidism on the development of the hypothalamo-pituitary-adrenal axis in the rat

Hypothyroid pups were obtained by adding methimazole in the mother's drinking water from day 15 of gestation and sacrificed at 4, 8 or 15 days. Circulating corticosterone decreased at all ages, while CBG concentrations diminished at day 4, increased at day 8 and did not change at day 15 in hypothyroid rats. As opposed to controls, plasma ACTH concentrations decreased steadily with age while there was an accumulation of ACTH in the anterior pituitary of hypothyroid 15-day-old rats. Anterior pituitary POMC contents were unaffected by the treatment. In the hypothalamic PVN, CRF mRNA levels in the total population of CRF-synthesizing cells and in the CRF +/AVP + subpopulation were below those of controls whatever the age considered while AVP mRNA in the CRF +/AVP + subpopulation did not change at day 4 and decreased at day 8 and 15 in hypothyroid animals. Both the number of cell bodies expressing detectable levels of CRF mRNA and the percentage of CRF and AVP colocalization decreased at day 4 and were unchanged thereafter. CRF and AVP immunoreactivity in the zona externa of the median eminence increased with age but was not affected by methimazole treatment. The concentration of AVP mRNA in the magnocellular cell bodies of the PVN and the SON as well as AVP immunoreactivity in the zona interna of the median eminence were not changed by the treatment at days 4 and 8. In hypothyroid 15-day-old rats, SON AVP mRNA increased, AVP immunoreactivity decreased while plasma osmolality was enhanced. In conclusion, our data demonstrate that experimental hypothyroidism impairs specifically the maturation of hypothalamic parvocellular CRF and AVP gene expression during the stress hyporesponsive period. These observations suggest that the physiological peak in plasma thyroxine concentrations that occur between day 8–12 may participate in the maturation of hypothalamic CRF- and AVP-synthesizing cells.

Effects of Experimental Hypothyroidism on 5-HT1A, 5-HT2A Receptors, 5-HT Uptake Sites and Tryptophan Hydroxylase Activity in Mature Rat Brain

The study was aimed at investigating the repercussions of deficiency in thyroid function with and without thyroid hormone (TH) replacement on the neurochemical entities which underly serotonin (5-HT) neutrotransmission, namely 5-HT_1A, 5-HT_2A receptors, 5-HT transporter and tryptophan hydroxylase (TPH) in the mature brain. Surgically thyroidectomized male Wistar rats received: (1) an iodine-free diet to produce severe hypothyroidism; (2) hormonal replacement with 15 µg/kg/day of thyroxine (T4) for 21 days to normalize serum TH levels, or (3) hormonal replacement with 200 µg/kg/day of T4 for 14 days to produce an excess of circulating THs. Sham-operated rats were used as controls. Neither hypothyroidism nor an excess in serum TH levels affected ³H-8-OH-DPAT binding to 5-HT_1A receptors, ³H-citalopram binding to 5-HT transporter and TPH activity in various brain structures indicating that, in the mature brain, the presynaptic entities of 5-HT neurotransmission are resistant to large variations in TH levels. By contrast, hypothyroid rats had a significant decrease in B_max of ³H-ketanserin binding to cortical 5-HT_2A receptors compared to controls. Cortical ³H-ketanserin binding in thyroidectomized rats was normalized after replacement with low-dose T4. Excess serum TH levels in thyroidectomized rats did not produce any changes in cortical 5-HT_2A receptors when compared to thyroidectomized rats with normalized TH levels. The present data suggest that the decrease in cortical 5-HT_2A receptors is the main neurochemical event underlying the impairing effect of hypothyroidism on 5-HT neurotransmission.

Effect of hypothyroidism on glucose transport and metabolism in rat small intestine

The effect of experimental hypothyroidism on the absorption, transmural transport and metabolism of glucose was studied by perfusion of isolated loops of rat jejunum in vitro. When expressed on a dry weight basis, the rate of absorption was enhanced by 32% ( P < 0.01); when expressed on a length basis there was no significant change, since the enhancement per unit weight was almost exactly compensated by a diminution in mass per unit length in the hypothyroid state. When expressed in either units, there was a significant enhancement in transmural transport (+123% and +77%, respectively, both P < 0.001), which reflected in part a diminution in the rate of glucose utilization (−29%, P < 0.01 and −43%, P < 0.001, respectively). The changes in glucose utilization were matched by changes in lactate production. Three factors contributed to the diminution in glucose utilization in the hypothyroid state: a diminution in the concentration of 6-phosphofructo-1-kinase (−35%, P < 0.05), and increase in the S 0.5 of 6-phosphofructo-1-kinase for fructose 6-phosphate from 0.4 to 0.6 mM and a fall in the mucosal concentration of fructose 2,6-bisphosphate (−56%, P < 0.05). From the point of view of the whole animal, there is little if any change in the capacity of the intestine to absorb glucose from the lumen, but there is a large enhancement of transmural transport that is metabolically driven.

Effect of experimental hypothyroidism on the control of 6-phosphofructo-1-kinase activity in rat jejunal mucosa

Changes in the activity of 6-phosphofructo-1-kinase (PFK, EC 2.7.1.11) from the epithelial cells of rat small intestine during experimental hypothyroidism were studied. Hypothyroism resulted in significant decreases in the plasma concentrations of total tri-iodothyronine, free tri-iodothyronine, total thyroxine, free thyroxine and insulin. These changes were associated with a significant increase in the plasma concentration of thyrotropin. The total activity and activity ratios (activity at 0.5 mM fructose 6-phosphate at pH 7.0/activity at pH 8.0 ( v 0.5/V)) of jejunal PFK of hypothyroid rats were significantly diminished as compared to control rats. PFK of hypothyroid rats was more sensitive to inhibition by ATP. The mucosal enzyme of both control and hypothyroid state was sensitive to stimulation by AMP and fructose 2,6-bisphosphate. It is concluded that during hypothyroidism the rate of glycolytic pathway in the small intestine is reduced as a result of a fall in glucose uptake, and the subsequent kinetic changes of PFK are primarily to maintain the concentrations of fructose 6-phosphate (and glucose 6-phosphate) during the reduced glycolytic flux. These changes in PFK activity may be caused by changes in plasma insulin concentrations, glucose utilization and fructose 2,6-biphosphate concentrations.

The effect of experimental hypothyroidism on phosphofructokinase activity and fructose 2,6-bisphosphate concentrations in rat heart.

Experimental hypothyroidism was induced in rats by the administration of NaClO4. Hearts from normal and hypothyroid rats were homogenized, and the extracts were assayed for phosphofructokinase-1 and phosphofructokinase-2 activity and fructose 2,6-bisphosphate concentrations. Hypothyroidism was associated with a drastic loss of phosphofructokinase-1 activity. A hyperbolic relationship between plasma thyroxine concentrations and phosphofructokinase-1 activity was found. As treatment with NaClO4 progressed, the decrease in blood thyroxine was faster than the decrease in enzyme activity. After prolonged hypothyroidism (a decrease in thyroxine of more than 10-fold), a 4-fold decrease in phosphofructokinase-1 activity was observed. In this metabolic condition 2-fold decreases in phosphofructokinase-2 activity and in fructose 2,6-bisphosphate were observed. A similar decrease in phosphofructokinase-1 activity in a partially purified preparation was found. The addition of L-thyroxine in the diet had little effect on phosphofructokinase-1 activity. However, exposure of minced pieces of hearts of hypothyroid rats to tri-iodothyronine for 5 h resulted in a clear increase in phosphofructokinase-1 activity, which was partially prevented by the simultaneous addition of cycloheximide. These results could account for the decrease in carbohydrate metabolism in heart from hypothyroid rats.

Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver

The effect of experimental hypothyroidism on the catabolism of plasma lipoproteins and on the expression of low density lipoprotein receptors by the liver was investigated in rats made hypothyroid by surgery. The animals developed mild hypercholesterolemia, mainly due to an increase of plasma low density lipoprotein, while other lipoprotein classes were only marginally affected. Kinetic studies using [ 125I]LDL indicated that a decreased fractional catabolic rate of the lipoprotein was responsible for this finding in agreement with the in vitro observation of a reduced binding of lipoproteins to liver membranes from hypothyroid rats and with the demonstration, by ligand blotting analysis, of a decreased expression of lipoprotein receptors in liver membranes. These data suggest that hypothyroidism affects lipoprotein distribution also by decreasing the catabolism of low density lipoproteins by the liver.

Effect of experimental hypothyroidism on hearing in adult guinea pigs.

A group of guinea pigs was rendered hypothyroid using propylthiouracil solution in their drinking water. The animals were hypothyroid for at least 120 days. During this time no change was noted in their hearing thresholds for high-frequency clicks. The audiometric evaluation was performed using brainstem evoked response audiometry.

The effect of experimental hypothyroidism on coronary blood flow and hemodynamic factors

A reduction in the basal metabolism rate and protein bound iodine conversion ratio in a group of dogs following the administration of I 131 was accepted as evidence of experimentally induced hypothyroidism. Observations of cardiac functions were made in the normal control group and in the hypothyroid group. The latter group was characterized by a reduction in coronary sinus blood flow, left ventricular oxygen consumption and heart rate. Atropine increased each of these values in the hypothyroid animals to a level approximately equal to that induced by atropine in the normal control group. The ability of the hypothyroid heart to raise coronary sinus blood flow and left ventricular oxygen consumption to the level of the normal heart in response to atropine is explained in terms of changes in heart rate because a close association between heart rate and these two functions has been established under a wide variety of experimental conditions. The capacity of the hypothyroid heart to change its rate appears to be unimpaired. The cardiac index of the hypothyroid heart is also reduced but fails to return to the normal control levels in response to atropine. This reduction is probably associated with an increase in A-V oxygen difference, indicating a relatively greater reduction in cardiac output than in total oxygen consumption.

Effect of Experimental Hypothyroidism on Period of Gestation in the Rabbit.

In some unpublished data obtained in this laboratory, it was found that thyroid removal in the pregnant female albino rat resulted in abortion or resorption of the foetuses, provided this operation was done before the first two-thirds of the gestation period. Because the rabbit possesses a somewhat different type of ovarian activity than does the rat, it was thought to be of interest to determine whether the pregnant female rabbit would react to thyroidectomy in a similar manner. The results of this preliminary study indicate that contrary to the reaction obtained in the rat, thyroid removal has little if any effect on the period of gestation in the rabbit. Although 33 New Zealand does, ranging in age from 7 to 18 months, were used as experimental animals, complete data on only 15 are reported here. The results on the remaining 18 animals will be reported when the data are completed. Ten additional normal females served as controls. Each doe was mated, being allowed to copulate twice, and the thyroid glands removed at definite intervals after mating. This interval in some cases was as short as 2 hours, while in other cases the time was extended to 12 days. The length of the period of gestation was then noted. The controls were mated but were not subjected to operative procedures and the duration of gestation also noted. As can be seen from Table I, no apparent differences between the length of the gestation period occurred in operated and unoperated animals. It appeared possible that all of the thyroidectomies might not have been complete, and that regeneration of thyroid remnants might have occurred. In 6 animals (Nos. 3, 7, 8, 34, 40, and 54) which were sacrificed, the entire thyroid region was removed, fixed, and a careful search made for traces of thyroid tissue under a binocular dissecting microscope.