Increased pituitary thyroxine 5′-deiodinase activity in adult rats rendered hyper- or hypo-thyroid during perinatal life

1985 ◽  
Vol 63 (4) ◽  
pp. 279-282 ◽  
Author(s):  
Peter Walker
Keyword(s):  
Adult Rats ◽  
Feedback Effects ◽  
Adult Rat ◽  
Gland Weight ◽  
Deiodinase Activity ◽  
Body Weights ◽  
Tsh Secretion ◽  
Neonatal Hyperthyroidism ◽  
Perinatal Hypothyroidism ◽  
And Control

Perinatal thyroid dysfunction in the rat leads to permanent alterations in pituitary TSH secretion in the adult animal. Thus, neonatal hyperthyroidism (NH) and perinatal hypothyroidism (PH) both result in apparent increased pituitary sensitivity to the feedback effects of thyroid hormones in the adult rat. To determine if increased intrapituitary generation of triiodothyronine (T3) might account for these observations, we measured thyroxine (T4) 5′-deiodinase activity in pituitary homogenates of adult NH and PH rats. NH was induced by injecting neonatal rats with 12 daily sc injections of T4 (0.4 μg/g body weight (BW)). Control rats received vehicle alone. PH was induced by administering 0.05% 6-n-propylthiouracil in the drinking water to pregnant dams from the 16th day of gestation through the 12th day postpartum. Thereafter, a normal water supply was substituted. NH and PH rats were allowed to mature and were sacrificed at 105 days of age. Serum T4, T3, and TSH concentrations were measured by radioimmunoassay. Pituitary T4 5′-deiodinase activity was assessed by the measurement of T3 formation by pituitary homogenates incubated in the presence of 0.65 μM T4 and 100 mM dithiothreitol at 37 °C for 90 min. Body weights of adult NH and PH rats were slightly but not significantly decreased compared with control rats. Relative pituitary gland weight (milligrams per 100 g BW) was significantly decreased in adult PH rats (P < 0.005) but not in adult NH rats. In adult NH rats, serum T4 and T3 concentrations were significantly decreased (P < 0.01) compared with control rats. Serum TSH concentrations were similar. No significant differences in serum T4, T3, and TSH concentrations were noted between adult PH and control rats. Pituitary T4 5′-deiodinase activity was significantly increased in both adult NH and PH rats compared with controls (NH > PH > control; P < 0.005, and P < 0.05, respectively). These data indicate that pituitary T4 5′-deiodinase activity is significantly increased in adult NH and PH rats. Increased pituitary T4 5′-monodeiodination may explain, in part, the apparent increased thyrotroph sensitivity to feedback effects of thyroid hormone in these animals.

scholarly journals Effects of thyroidectomy, T4, and DITPA replacement on brain blood vessel density in adult rats

2008 ◽  
Vol 294 (5) ◽  
pp. R1504-R1509 ◽  
Author(s):  
Evelyn Heymann Schlenker ◽  
Megan Hora ◽  
Yingheng Liu ◽  
Rebecca A. Redetzke ◽  
Eugene Morkin ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Vessel ◽  
Cardiac Function ◽  
Blood Vessels ◽  
Treated Group ◽  
P Value ◽  
Adult Rats ◽  
Adult Rat ◽  
Body Weights ◽  
And Function

In hypothyroid patients, altered microvascular structure and function may affect mood and cognitive function. We hypothesized that adult male hypothyroid rats will have significantly lower forebrain blood vessel densities (BVD) than euthyroid rats and that treatment with 3,5-diiothyroprionic acid (DITPA) (a thyroid hormone analog) or thyroxine (T4) will normalize BVDs. The euthyroid group received no thyroidectomy or treatment. The other three groups received thyroidectomies and pellets. The hypothyroid group received a placebo pellet, the DITPA group received an 80-mg DITPA-containing pellet, and the T4 group received a 5.2-mg T4 slow-release pellet for 6 wk. Body weights, cardiac function, and body temperatures were measured. A monoclonal antiplatelet endothelial cell adhesion antibody was used to visualize blood vessels. The euthyroid group averaged body weights of 548 ± 54 g, while the hypothyroid group averaged a body weight of 332 ± 19 g ( P value < 0.001). Relative to the euthyroid group, the DITPA-treated group was significantly lighter ( P value < 0.05), while the T4-treated group was comparable in body weight to the euthyroid group. The same trends were seen with body temperature and cardiac function with the largest difference between the euthyroid and hypothyroid groups. BVD in the euthyroid group was 147 ± 12 blood vessels/mm2 and in hypothyroid group 69 ± 5 blood vessels/mm2 ( P = 0.013) but similar among the euthyroid, DITPA, and T4 groups. These results show that hypothyroidism decreased BVD in adult rat forebrain regions. Moreover, DITPA and T4 were efficacious in preventing effects of hypothyroidism on cardiac function and BVD.

scholarly journals Toxicology of Repeated Iodine Thyroid Blocking in Adult Rat

2018 ◽  
Vol 3 (1) ◽  
Keyword(s):  
Single Dose ◽  
Late Onset ◽  
Repeated Administration ◽  
Nuclear Accidents ◽  
Adult Rats ◽  
Adult Rat ◽  
Safety Studies ◽  
Thyroid Morphology ◽  
And Control

Radioactive iodines emitted following nuclear accidents are responsible for the dramatic increase of the late-onset thyroid cancer. Until the Fukushima disaster, a single dose of potassium iodide (KI) has been considered as an efficient countermeasure. Indeed, recently it has been suggested that repeated administration of KI may be necessary to ensure adequate protection in case of protracted exposure. Whereas, the effect of a single dose of KI has largely been studied ensuring its safety, studies regarding adverse effects of repeated iodine thyroid blocking (ITB) administration are scarce. Our objective was to assess the long term overall impact of KI in adult rats after repeated intake. Adult Wistar rats were subjected to either KI or saline solution over eight days. Biochemical homeostasis, hormones level, autoimmunity status, thyroid morphology and thyroid transcriptome profile were analyzed thirty days after the discontinuation of KI administration. Biochemical parameters, plasma levels of TSH; thyroid hormones; anti-TPO and anti-Tg did not differ between treated and control rats, the thyroid histology was not affected by the treatment and no long term transcriptome signature attributable to the treatment was noticed. Based on these data, we conclude the safety of repeated KI intake in adult rats; these data are prominent and may contribute to the ongoing development of KI guidelines and marketing authorization.

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

1984 ◽  
Vol 105 (1) ◽  
pp. 31-39 ◽  
Author(s):  
M. E. Besa ◽  
A. M. Pascual-Leone
Keyword(s):  
Saline Control ◽  
Hypothalamic Lesions ◽  
Tsh Secretion ◽  
Tsh Regulation ◽  
Neonatal Hyperthyroidism ◽  
And Control ◽  
Two Populations ◽  
Tsh Levels

Abstract. The neo-T4 syndrome was induced in rats by administration of 30 μg 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 μg 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 neoT4 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.

EFFECT OF EXPERIMENTALLY INDUCED THYROIDITIS ON BIOSYNTHESIS OF THYROXINE IN RATS

1969 ◽  
Vol 62 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Colum A. Gorman ◽  
James W. Anderson ◽  
Eunice V. Flock ◽  
Charles A. Owen ◽  
Khalil G. Wakim
Keyword(s):  
Intravenous Administration ◽  
Hashimoto's Thyroiditis ◽  
Sprague Dawley ◽  
Thyroid Extract ◽  
Histologic Appearance ◽  
Gland Weight ◽  
Sprague Dawley Rats ◽  
Thyroid Glands ◽  
And Control ◽  
Experimentally Induced

ABSTRACT Thyroiditis was induced in Sprague-Dawley rats by repeated immunization with thyroid extract and Freund's adjuvant. Immunized and control animals were killed at intervals up to 6 hours after intravenous administration of 131I as iodide at 5, 8 and 10 weeks after the first injection. Radioiodinated compounds in the thyroid glands were identified chromatographically. Evidence of moderate thyroiditis was present (histologic appearance, gland weight, and protein-bound iodine-butanol-extractable iodine difference) but the rate of incorporation of radioiodide into thyroxine, the percentage of radioactivity in the gland as iodide, and the MIT/DIT ratio were not significantly different in immunized and control animals. The MIT/DIT ratio was found to vary with time after 131I administration in both immunized and control animals. These studies did not uncover a defect in organification of iodide in experimental thyroiditis similar to that described by others in humans with Hashimoto's thyroiditis.

The impact of maternal protein restriction during perinatal life on the response to a septic insult in adult rats

2020 ◽  
pp. 1-8
Author(s):  
Reza Khazaee ◽  
Anastasiya Vinokurtseva ◽  
Lynda A. McCaig ◽  
Cory Yamashita ◽  
Daniel B. Hardy ◽  
...  
Keyword(s):  
Control Diet ◽  
Protein Restriction ◽  
Saline Control ◽  
Female Adult ◽  
Adult Rats ◽  
Male And Female ◽  
Maternal Protein Restriction ◽  
And Control ◽  
The Impact ◽  
Septic Insult

Abstract Although abundant evidence exists that adverse events during pregnancy lead to chronic conditions, there is limited information on the impact of acute insults such as sepsis. This study tested the hypothesis that impaired fetal development leads to altered organ responses to a septic insult in both male and female adult offspring. Fetal growth restricted (FGR) rats were generated using a maternal protein-restricted diet. Male and female FGR and control diet rats were housed until 150–160 d of age when they were exposed either a saline (control) or a fecal slurry intraperitoneal (Sepsis) injection. After 6 h, livers and lungs were analyzed for inflammation and, additionally, the amounts and function of pulmonary surfactant were measured. The results showed increases in the steady-state mRNA levels of inflammatory cytokines in the liver in response to the septic insult in both males and females; these responses were not different between FGR and control diet groups. In the lungs, cytokines were not detectable in any of the experimental groups. A significant decrease in the relative amount of surfactant was observed in male FGR offspring, but this was not observed in control males or in female animals. Overall, it is concluded that FGR induced by maternal protein restriction does not impact liver and lung inflammatory response to sepsis in either male or female adult rats. An altered septic response in male FGR offspring with respect to surfactant may imply a contribution to lung dysfunction.

PRE-MATERNAL ISOLATION EFFECTS ON BEHAVIOUR AND ENDOCRINE FUNCTION OF OFFSPRING

1969 ◽  
Vol 62 (2) ◽  
pp. 367-384 ◽  
Author(s):  
A. M. Sackler ◽  
A. S. Weltman ◽  
R. Schwartz ◽  
P. Steinglass
Keyword(s):  
Locomotor Activity ◽  
Growth Rates ◽  
Female Offspring ◽  
The Body ◽  
Endocrine Function ◽  
Male And Female ◽  
Isolation Stress ◽  
Developmental Growth ◽  
Body Weights ◽  
And Control

ABSTRACT This report was designed to determine combined effects of maternal endocrine imbalances and abnormal behaviour due to prolonged isolation stress of female mice on the behaviour, developmental growth rate and endocrine function of their offspring. Sixty female albino mice averaging 19 g were divided equally into isolated and control groups. The isolated females were housed singly; control females were maintained in groups of 2 mice per cage. After observation of behavioural and physiological effects characteristic of isolation stress in the test mice, all isolated and control mice were mated after a 6½ month experimental, isolation period. No differences were observed in fertility and fecundity of the two groups of mothers. Analyses of developmental growth rates of the litters of the isolated versus control mothers showed significantly lower body weights in the test offspring at 3 and 4 weeks of age. The body weights of the female offspring remained significantly lower from the 4th to 11th weeks. The effects on the body weights of the male offspring declined and were no longer statistically significant at the 5th to 11 weeks. Locomotor activity at 4½ and 8 weeks of age was markedly or significantly higher in the male and female mice from isolated mothers. Tail-blood samples taken prior to autopsy at 5 and 11 weeks of age revealed significant decreases in the total leukocyte and eosinophil counts of both sexes. At the two ages, the absolute and relative spleen and thymus weights of the male and female offspring were markedly and/or significantly lower than the values observed in counterpart young from control females. Significant decreases were also observed in the absolute gonadal organ weights of both sexes at 11 weeks of age. The various data indicated inhibited growth rates, heightened locomotor activity and evasiveness, as well as evidence of increased adrenocortical function in the offspring from test mothers. The gonadal weight decreases suggested retarded gonadal development. Further studies using split-litter techniques are required to differentiate the effects of prenatal endocrine imbalances versus postnatal maternal influence (i. e., nursing care) on the offspring.

scholarly journals Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induced inhibition of thyrotropin secretion in hypothyroid rats

2005 ◽  
Vol 153 (3) ◽  
pp. 429-434 ◽  
Author(s):  
P Cettour-Rose ◽  
T J Visser ◽  
A G Burger ◽  
F Rohner-Jeanrenaud
Keyword(s):  
Specific Inhibitor ◽  
Adult Rats ◽  
Reverse T3 ◽  
Brown Adipose ◽  
Tsh Secretion ◽  
Serum T3 ◽  
Serum T4 ◽  
Serum Tsh ◽  
Tsh Levels

Objectives: Intrapituitary triiodothyronine (T3) production plays a pivotal role in the control of TSH secretion. Its production is increased in the presence of decreased serum thyroxine (T4) concentrations and the enzyme responsible, deiodinase type 2 (D2), is highest in hypothyroidism. In order to document the role of this enzyme in adult rats we developed an experimental model that inhibited this enzyme using the specific inhibitor, reverse T3 (rT3). Methods: Hypothyroidism was induced with propylthiouracil (PTU; 0.025 g/l in drinking water) which in addition blocked deiodinase type 1 (D1) activity, responsible for the rapid clearance of rT3 in vivo. During the last 7 days of the experiment, the hypothyroid rats were injected (s.c.) for 4 days with 0.4 or 0.8 nmol T4 per 100 g body weight (bw) per day. For the last 3 days, the same amount of T4 was infused via s.c. minipumps. In additional groups, 25 nmol rT3/100 g bw per day were added to the 3-day infusion of T4. Results: Infusion of 0.4 nmol T4/100 g bw per day did not affect the high serum TSH levels, 0.8 nmol T4/100 g bw per day decreased them to 57% of the hypothyroid values. The infusions of rT3 inhibited D2 activity in all organs where it was measured: the pituitary, brain cortex and brown adipose tissue (BAT). In the pituitary, the activity was 27%, to less than 15% of the activity in hypothyroidism. Despite that, serum TSH levels did not increase, serum T4 concentrations did not change and the changes in serum T3 were minimal. Conclusions: We conclude that in partly hypothyroid rats, a 3-day inhibition of D2 activity, without concomitant change in serum T4 and minimal changes in serum T3 levels, is not able to upregulate TSH secretion and we postulate that this may be a reflection of absent or only minimal changes in circulating T3 concentrations.

scholarly journals HOMOLOGOUS DISEASE IN THE ADULT RAT, A MODEL FOR AUTOIMMUNE DISEASE

1963 ◽  
Vol 118 (4) ◽  
pp. 635-648 ◽  
Author(s):  
Peter Stastny ◽  
Vernie A. Stembridge ◽  
Morris Ziff
Keyword(s):  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Connective Tissue Diseases ◽  
Skin Lesions ◽  
Cutaneous Lesions ◽  
Adult Rats ◽  
Hydropic Degeneration ◽  
Skin Changes ◽  
Adult Rat ◽  
The One

The cutaneous lesions of adult rats with homologous disease are described, and evidence is presented to indicate that they have an immunologic basis. The skin changes included erythema, purpura, edema, and a variety of inflammatory lesions. In the more active lesions, dermal infiltration, hydropic degeneration, acanthosis, and atrophy of the epidermis with hyperkeratosis and follicular plugging were present. In some cases, ulceration and sloughing were also observed. More chronic lesions were characterized by atrophy of the epidermis and collagenization of the dermis with disappearance of the skin appendages. Rejection of autografts was observed simultaneously with acceptance of homografts. The histologic appearance of autografts undergoing rejection was similar to that of the spontaneous skin lesions, suggesting that the latter, too, had an immunologic basis. In favor of this, also, was the specificity of the dermatitis for the skin of the host, with sparing of neighboring homograft tissue. There was a histologic similarity between the spontaneous skin lesions of homologous disease and those of lupus erythematosus on the one hand, and scleroderma on the other, thus supporting the possibility that the cutaneous lesions of these connective tissue diseases of man may also have an immunologic basis. It was concluded that the adult rat with homologous disease may furnish a model for human autoimmune disease.

Hyperthyroid adult rat cardiomyocytes. I. Nucleotide content, beta- and alpha-adrenoreceptors, and cAMP production

1989 ◽  
Vol 257 (5) ◽  
pp. C948-C956 ◽  
Author(s):  
C. M. Hohl ◽  
S. Wetzel ◽  
R. H. Fertel ◽  
D. K. Wimsatt ◽  
G. P. Brierley ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Adenine Nucleotide ◽  
Phosphodiesterase Inhibitor ◽  
Cardiac Cells ◽  
Beta Agonist ◽  
Camp Production ◽  
Adult Rats ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Half Maximal Effective Concentration

Ventricular myocytes isolated from the hypertrophied hearts of thyrotoxic adult rats have an increase in mean protein content per myocyte (6.3 +/- 0.2 vs. 4.4 +/- 0.2 ng) compared with euthyroid cells. Viability and adenine nucleotide profiles are similar in both populations, but NAD content of the hyperthyroid myocytes is depressed (4.9 +/- 0.2 vs. 5.5 +/- 0.2 nmol/mg for controls) and UTP is higher (1.2 +/- 0.09 vs. 0.9 +/- 0.04 nmol/mg). Binding of (-)-[125I]iodocyanopindolol to intact hyperthyroid myocytes is increased by 42% compared with controls, with no change in the dissociation constant (Kd). This elevation in beta-receptor number is correlated to enhanced beta-agonist-induced adenosine 3',5'-cyclic monophosphate (cAMP) production. The half-maximal effective concentration (EC50) for the euthyroid isoproterenol dose-response curve is 2.14 x 10(-7) M but is decreased to 2.51 x 10(-8) M in hyperthyroid cardiac cells. Basal adenylate cyclase activity is apparently not affected by thyroid hormones, since basal cAMP levels for both groups are identical (5 pmol/mg) and both rise roughly twofold in the presence of a phosphodiesterase inhibitor. Forskolin-induced cAMP production and cAMP-specific phosphodiesterase activity are similar as well. In contrast to beta-adrenergic response, there are no significant differences in alpha 1-antagonist [3H]prazosin binding parameters between hyperthyroid and euthyroid cardiomyocytes.

scholarly journals Competition of glycerol with other oxidizable substrates in rat brain

1986 ◽  
Vol 237 (1) ◽  
pp. 47-51 ◽  
Author(s):  
M C McKenna ◽  
L I Bezold ◽  
S J Kimatian ◽  
J T Tildon
Keyword(s):  
Rat Brain ◽  
Glutamine Metabolism ◽  
Glycerol Oxidation ◽  
Adult Rats ◽  
Adult Rat ◽  
Rat Pups ◽  
Age Related ◽  
Adult Rat Brain ◽  
14Co2 Production ◽  
Age Related Changes

The rate of conversion of [1,3-14C]glycerol into 14CO2 was measured in the presence and absence of unlabelled alternative substrates in whole homogenates from the brains of young (4-6 and 18-20 days old) and adult rats. Unlabelled glucose decreased 14CO2 production from [1,3-14C]glycerol by about 40% at all ages studied. Unlabelled 3-hydroxybutyrate significantly decreased the 14CO2 production from both low (0.2 mM) and high (2.0 mM) concentrations of glycerol in 4-6- and 18-20-day-old rat pups. However, the addition of 3-hydroxybutyrate had no effect on the rate of 14CO2 production from 2.0 mM-glycerol in adult rats, suggesting that the interaction of 3-hydroxybutyrate with glycerol in adult rat brain is complex and may be related to the biphasic kinetics previously reported for glycerol oxidation. Unlabelled glutamine decreased the production of 14CO2 by brain homogenates from 18-20-day-old and adult rats, but not in 4-6-day-old rat pups. In the converse situation, the addition of unlabelled glycerol to whole brain homogenates had little effect on the rate of 14CO2 production from [6-14C]glucose, 3-hydroxy[3-14C]butyrate and [U-14C]glutamine, although some significant differences were noted. Collectively these results suggest that glycerol and these other substrates may be metabolized in separate subcellular compartments in brain such that the products of glucose, 3-hydroxybutyrate and glutamine metabolism can dilute the oxidation of glycerol, but the converse cannot occur. The data also demonstrate that there are complex age-related changes in the interaction of glycerol with 3-hydroxybutyrate and glutamine. The fact that glycerol oxidation was only partially suppressed by the addition of 1-5 mM-glucose, -3-hydroxybutyrate or -glutamine could also suggest that glycerol may be selectively utilized as an energy substrate in some discrete brain region.

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