Effects Of Thyroid Hormone Deficiency Research Articles

Neonatal screening for primary and central congenital hypothyroidism: is it time to go Dutch?

Thyroid hormone (TH) is indispensable for brain development in utero and during the first two to three years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonatal screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroid-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterised by low TH concentrations while TSH is normal, low or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH-based thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a unique T4-TSH-thyroxine-binding globulin (TBG) NBS algorithm for CH which enables detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hypothyroidism instead of mild, and that early detection of central CH by NBS problably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

Therapeutic effect of biosynthesized silver nanoparticles on hypothyroidism induced in albino rats

BackgroundIn this study, silver nanoparticles (AgNPs) were biosynthesized using Rhizopus oryzae. The therapeutic effect of AgNP treatment protocols for hypothyroidism induced in male albino rats via biochemical as well as hematological parameters, thyroid profile, and androgen male sex hormone (testosterone) was evaluated. ResultsFTIR, XRD, TEM, DLS, SEM, and EDX were used to comprehensively characterize the biosynthesized AgNPs. The AgNPs have a 17–35 nm diameter, according to the results of their characterization. The average size detected by XRD was 37.96 nm, while the average size of the biosynthesized AgNPs was 78 nm determined by DLS analysis. Furthermore, ALT, AST activity, urea, creatinine, and TSH levels revealed a significant increase in the untreated hypothyroidism group according to potassium dichromate-induced hypothyroidism compared to the normal control group. The untreated hypothyroidism group's FT3, FT4, and albumin levels, however, significantly decreased when compared to the normal control group. In contrast, when compared to the hypothyroidism-untreated group, the mean values of FT3, FT4, and TSH were all significantly higher and TSH was significantly lower in the hypothyroidism AgNPS-treated group. Furthermore, T. testosterone and F. testosterone levels revealed a significant decrease in untreated hypothyroidism group when compared to the normal control group. Contrarily, F. testosterone levels in the hypothyroidism-treated group were much higher than those in the hypothyroidism-untreated group. ConclusionsAgNPs were successfully biosynthesized which exhibited therapeutic potential to increase thyroid hormone levels and avoid the biochemical side effects of thyroid hormone deficiency in the animal model of hypothyroidism.How to cite: Saied E, Hussein AS, Al-Askar AA, et al. Therapeutic effect of biosynthesized silver nanoparticles on hypothyroidism induced in albino rats. Electron J Biotechnol 2023;65. https://doi.org/10.1016/j.ejbt.2023.06.001.

Hypothyroidism, skin changes, and methods of skin care

Hypothyroidism mainly affects adults. The improper functioning of the thyroid gland results in hormone deficiency, and the slowdown of the metabolism of the whole body and skin changes. The study aimed to present, based on a literature review, skin symptoms occurring in hypothyroidism and substances that can reduce the adverse effects of thyroid hormone deficiency, and support skin care. The cosmetics rich in moisturizing ingredients, antioxidants, keratolytic, and immunomodulating substances are recommended to strengthen the skin barrier.

The Consensus on the Diagnosis and Management of Congenital Hypothyroidism in Term Neonates.

Congenital hypothyroidism (CH) is one of the most treatable endocrine disorders in infants and children that can influence the function of many organs in the body. On-time diagnosis and treatment can prevent the adverse effects of thyroid hormone deficiency on the child's neurodevelopment. There are many challenges in screening, post-screening, diagnosis, and managing this disorder. Therefore, this article aimed to mention updated information on this issue. Although there are different approaches for the treatment of hypothyroidism, the authors decided to create a national approach based on the conditions of our country.

Thyroid Hormone Deficiency Suppresses Fetal Pituitary-Adrenal Function Near Term: Implications for the Control of Fetal Maturation and Parturition.

Background: The fetal hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the control of parturition and maturation of organ systems in preparation for birth. In hypothyroid fetuses, gestational length may be prolonged and maturational processes delayed. The extent to which the effects of thyroid hormone deficiency in utero on the timing of fetal maturation and parturition are mediated by changes to the structure and function of the fetal HPA axis is unknown. Methods: In twin sheep pregnancies where one fetus was thyroidectomized and the other sham-operated, this study investigated the effect of hypothyroidism on circulating concentrations of adrenocorticotrophic hormone (ACTH) and cortisol, and the structure and secretory capacity of the anterior pituitary and adrenal glands. The relative population of pituitary corticotrophs and the masses of the adrenal zones were assessed by immunohistochemical and stereological techniques. Adrenal mRNA abundances of key steroidogenic enzymes and growth factors were examined by quantitative polymerase chain reaction. Results: Hypothyroidism in utero reduced plasma concentrations of ACTH and cortisol. In thyroid-deficient fetuses, the mass of corticotrophs in the anterior pituitary gland was unexpectedly increased, while the mass of the zona fasciculata and its proportion of the adrenal gland were decreased. These structural changes were associated with lower adrenocortical mRNA abundances of insulin-like growth factor (IGF)-I and its receptor, and key steroidogenic enzymes responsible for glucocorticoid synthesis. The relative mass of the adrenal medulla and its proportion of the adrenal gland were increased by thyroid hormone deficiency in utero, without any change in expression of phenylethanolamine N-methyltransferase or the IGF system. Conclusions: Thyroid hormones are important regulators of the structure and secretory capacity of the pituitary-adrenal axis before birth. In hypothyroid fetuses, low plasma cortisol may be due to impaired adrenocortical growth and steroidogenic enzyme expression, secondary to low circulating ACTH concentration. Greater corticotroph population in the anterior pituitary gland of the hypothyroid fetus indicates compensatory cell proliferation and that there may be abnormal corticotroph capacity for ACTH synthesis and/or impaired hypothalamic input. Suppression of the development of the fetal HPA axis by thyroid hormone deficiency may contribute to the delay in fetal maturation and delivery observed in hypothyroid offspring.

Hypothyroidism effects on the morpho-histometrical features of testes in adult rats

Background: Up until now, the effect of thyroid hormones on the male reproductive organ, after puberty, is not well understood. OBJECTIVES: In the present study, the morpho-histometrical effects of thyroid hormone deficiency on the adult-male rat reproductive organs were investigated. MATHODS: Thirty adult male rats were randomly divided into three groups (n=10): control, hypothyroid, and hypothyroid which receives Levothyroxine. After 4-months we examined the number of spermatogonia cells, primary spermatocytes, and Sertoli cells, as well as the seminiferous tubules epithelium thickness, area of seminiferous tubules, and the diameter and thickness of testis artery walls. RESULTS: No significant difference was observed between the hypothyroid and control rats in terms of the area of seminiferous tubules, the number of spermatogonia cells, primary spermatocytes, and Sertoli cells. Moreover, the epithelium thickness of seminiferous tubules and the diameter and thickness of artery walls were significantly decreased in hypothyroid group compared with the control rats. CONCLUSIONS: These observations are consistent with the hypothesis that hypothyroidism can affect the male fertility and declare that it may influence male reproduction by reducing the testis blood flow.

The effect of thyroid hormone deficiency on erythropoiesis in dogs

This research aimed to evaluate the effect of thyroid hormone deficiency on the erythrocytic system in dogs. Dogs with clinical symptoms of hypothyreosis such as obesity, hyperpigmentation, and lethargy were selected. The dogs demonstrating breed predisposition to hypothyreosis were incorporated in the analysis: Dachshunds, Retrievers, and mixed-breed dogs. A detailed history was taken and clinical, hormonal, biochemical and haematological blood tests were performed. Peripheral blood samples were taken from 53 dogs. Finally, the dogs with the initial T4 (thyroxine) concentration < 1.3 µg/dl and animals demonstrating clinical improvement after a 2-month therapy with levothyroxine at a dose of 10 µg/kg administeredper ostwo times a day were qualified. The animals between 10 months to 13 years of age were divided into two groups: clinically healthy (control group, n = 35) and dogs presenting clinical symptoms of hypothyreosis (experimental group, n = 18). In this research, the broadly described normocytic normochromic non-regenerative anaemia was not diagnosed in dogs with hypothyreosis. However, a positive correlation between T4 and red blood cell indices such as the average mass of haemoglobin per red blood cell, concentration of haemoglobin in a given volume of packed red blood cells as well as a negative correlation with haematocrit value was discovered in the experimental group after the 2-month therapy with levothyroxine. These results point to the influence of thyroid hormones on erythropoiesis. This observation is partially consistent with other studies, which noted the casual link between the changes in red blood cell system and the function of thyroid in dogs and humans.

Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant human growth hormone

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5-3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.

Experimental Hypothyroidism Delays Field Excitatory Post‐Synaptic Potentials and Disrupts Hippocampal Long‐term Potentiation in the Dentate Gyrus of Hippocampal Formation and Y‐Maze Performance in Adult Rats

Manipulations of thyroid hormones have been shown to influence learning and memory. Although a large body of literature is available on the effect of thyroid hormone deficiency on learning and memory functions during the developmental stage, electrophysiological and behavioural findings, particularly on propylthiouracil administration to adult normothyroid animals, are not satisfactory. The experiments in the present study were carried out on 12 adult male Wistar rats aged 6-7 months. Hypothyroidism was induced by administering 6-n-propyl-2-thiouracil in their drinking water for 21 days at a concentration of 0.05%. The spatial learning performance of hypothyroid and control rats was studied on a Y-maze. The rats were then placed in a stereotaxic frame under urethane anaesthesia. A bipolar tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted into the granule cell layer of the ipsilateral dentate gyrus to record field excitatory post-synaptic potentials. After a 15-min baseline recording of field potentials, long-term potentiation was induced by four sets of tetanic trains. The propylthiouracil-treated rats showed a significantly attenuated input-output (I/O) relationship when population spike (PS) amplitudes and field excitatory post-synaptic potentials (fEPSP) were compared. fEPSP and PS latencies were found to be longer in the hypothyroid group than in the control group. The PS amplitude and fEPSP slope potentiations in the hypothyroid rats were not statistically different from those in the control rats, except for the field EPSP slope measured in the post-tetanic and maintenance phases. The hypothyroid rats also showed lower thyroxine levels and poor performance in the spatial memory task. The present study provides in vivo evidence for the action of propylthiouracil leading to impaired synaptic plasticity, which might explain deficit in spatial memory tasks in adult hypothyroid rats.

Reproductive Effects of Prolonged Experimentally Induced Hypothyroidism in Bitches

Hypothyroidism has detrimental effects on reproduction in females of many species. Studies of hypothyroidism in bitches are limited and results conflicting. Hypothyroidism interferes with reproductive function and health of offspring in bitches. A total of 9 healthy mixed-breed bitches (control) and 9 mixed breed bitches with hypothyroidism induced by radioactive iodine administration. Dogs in both groups were bred 20.9 ± 4.0 and 56 ± 7.6 weeks after radioiodine administration in the hypothyroid group and again after levothyroxine was administered for 37 ± 14 weeks to hypothyroid dogs. Measures of the estrus cycle, fertility, gestation, whelping, and pup health were evaluated at each breeding. Comparisons were made between hypothyroid and control dogs as well as within groups between times. Pregnancy was documented in all dogs in both groups at the 1st breeding, 4/8 and 6/6 untreated hypothyroid and control dogs, respectively, at the 2nd breeding, and 6/6 and 5/6 treated hypothyroid and control dogs, respectively, at the 3rd breeding. Periparturient mortality was higher and birth weight was lower in pups born to untreated hypothyroid dogs compared with control dogs or treated hypothyroid dogs. There was no difference in interestrus interval, gestation duration, breeding behavior, interval between birth of pups, or serum progesterone concentrations at any breeding between or within groups. Resolution of hypothyroidism reversed the detrimental effects of thyroid hormone deficiency on reproduction. Hypothyroidism causes reversible periparturient mortality and low birth weight in offspring. Further investigation is necessary to determine if fertility is affected.

Experimentally Induced Hyperthyroidism Disrupts Hippocampal Long-Term Potentiation in Adult Rats

Background: Manipulating thyroid hormones has been shown to influence learning and memory. Although a large body of literature is available on the effects of thyroid hormone deficiency on learning and memory functions during developmental or adult-onset hypothyroidism, electrophysiological findings are limited. This limitation is especially notable with respect to thyroxine administration in adult, normothyroid animals. Methods: Experiments were carried out on 12 adult male Wistar rats, each 9–10 months of age. Rats were randomly divided into hyperthyroid (0.2 mg/kg/day intraperitoneal thyroxine injection, for 21 days) and control groups (n = 6 animals in each group). Following spatial learning performance tests on hyperthyroid and control groups, rats were anesthetized with urethane and placed in a stereotaxic frame. A bipolar, tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted within the granule cell layer of the ipsilateral dentate gyrus to record field excitatory postsynaptic potentials (fEPSP). Following a 15-min baseline recording of fEPSPs, long-term potentiation (LTP) was induced by four sets of tetanic pulse trains. Results: Thyroxine-treated rats showed significantly worse performance in the spatial memory task and attenuated input-output relationships in the electrophysiological analyses. Treated rats also showed a lower efficacy of LTP induction when compared with controls. Conclusion: The present study provides clear in vivo evidence for the action of L-thyroxine in the impairment of synaptic plasticity and in inducing spatial memory task deficits in adult rats. These findings may explain the complaints of cognitive function reductions in hyperthyroid patients.

Proliferating Cell Nuclear Antigen as a Molecular Biomarker for Spermatogenesis in PTU-Induced Hypothyroidism of Rats

The thyroid hormone has few serious effects on the testes except during the neonatal stage. There is little knowledge concerning the prolonged effect of thyroid hormone deficiency throughout the rat's life span and its effect on spermatogenesis. Proliferating cell nuclear antigen (PCNA) is a nuclear matrix protein, which is essential for multiple cell cycle pathways. Here we used PCNA immunohistochemistry as a marker to differentiate between the testes of control and hypothyroid rats. About 20 rats were equally divided into 2 groups; the first group was the control group, while the second group was the experimental group in which rats were fed 0.05% 6-n-propyl thiouracil (PTU) in drinking water for 6 weeks. Immunohistochemistry, using an antibody against PCNA, showed at least 3 differences in the pattern of PCNA immunoreactivity (PCNA-ir). First, PCNA-ir was not detected in Sertoli and Leydig cells in the testes of control rats and detected in some of the hypothyroid rats. Second, in the control group more than 96% of spermatogonia were PCNA-positive cells; however, hypothyroidism caused the reduction to approximately 25% PCNA staining in spermatogonia. The third difference was in the abnormal distribution of spermatogonia seen in the hypothyroid rat testis, not in the control one. These results suggest that prepubertal hypothyroidism affects the proliferation of spermatogenic cells leading to impaired spermatogenesis and that PCNA index is a useful marker for assessing germ cell kinetics and spermatogenesis in prepubertal hypothyroidism.

Neural response to transcranial magnetic stimulation in adult hypothyroidism and effect of replacement treatment

Purpose Despite clinical evidences that hypothyroidism is often associated with cognitive dysfunction, affective disorders and psychosis, the effects of thyroid hormone deficiency on the adult brain have been largely unexplored. We investigated the hypothesis that hypothyroidism might affect cortical excitability and modulates inhibitory and excitatory cortical circuits by using Transcranial Magnetic Stimulation. Materials and methods Cortical excitability was probed in 10 patients with overt hypothyroidism and 10 age-matched healthy controls. We tested motor thresholds and corticospinal excitability, cortical silent period and peripheral silent period, short interval intracortical inhibition, intracortical facilitation. Patients were evaluated at the time of diagnosis, as well as after 3 and 6 months replacement therapy with l-thyroxin. Results At baseline, patients showed decreased cortical excitability, with increased resting and active motor threshold and decreased steepness of the motor evoked potential recruitment curves. These changes were paralleled by longer cortical silent period and decreased short interval intracortical inhibition. After 3 months replacement therapy, all the parameters but short interval intracortical inhibition were restored to normal values. Short interval intracortical inhibition returned to normal values only after 6 months of replacement therapy. Conclusions Thyroid hormones are needed to modulate cortical excitability and cortical inhibitory circuits in adults.

Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor α

Thyroid hormone insufficiency leads to impaired neurogenesis, behavioral alterations and cognitive deficits. Thyroid hormone receptors, expressed in brain regions involved in these behaviors, mediate the effects of thyroid hormone deficiency or excess. To determine the contribution of thyroid hormone receptor alpha (TRα) in these behaviors, we examined the behavior of euthyroid as well as hypo- and hyperthyroid mice lacking all isoforms of the TRα (TRα o/o). The hypothyroxinemic TRα o/o mice demonstrated behavioral inhibition, manifested in decreased activity and increased anxiety/fear in the open field test (OFT) and increased immobility in the forced swim test (FST) compared to C57BL/6J mice. TRα o/o mice also showed learning and recall impairments in the Morris water maze (MWM), which were exaggerated by hypothyroidism in TRα o/o mice. These impairments were concurrent with increased thigmotaxis, suggesting an increased anxiety-like state of the TRα o/o mice in the MWM. Expression of genes, known to be involved in processes modulating learning and memory, such as glucocorticoid receptor (GR), growth-associated protein 43 (GAP-43) and neurogranin (RC3), were significantly decreased in the hippocampus of TRα o/o mice. GR expression was also decreased in the frontal cortex and amygdala of TRα o/o mice, indicating that expression of GR is regulated, probably developmentally, by one or more isoforms of TRα in the mouse brain. Taken together these data demonstrate behavioral alterations in the TRα o/o mice, indicating the functional role of TRα, and a delicate interaction between TRα and TRβ-regulated genes in these behaviors. Thyroid hormone-regulated genes potentially responsible for the learning deficit found in TRα o/o mice include GR, RC3 and GAP-43.

Increased Pro-Nerve Growth Factor and p75 Neurotrophin Receptor Levels in Developing Hypothyroid Rat Cerebral Cortex Are Associated with Enhanced Apoptosis

Thyroid hormone insufficiency adversely affects cortical development; however, its effect on apoptosis modulation during cerebral cortex development is not understood. We investigated the effect of perinatal hypothyroidism on apoptosis and its mechanisms during rat cerebral cortex development. Primary hypothyroidism was induced by feeding methimazole (0.025% wt/vol) in the drinking water to pregnant and lactating rats and continued until the animals were killed (hypothyroid group). Cerebral cortices from pups were harvested at different postnatal ages (postnatal d 0, 8, 16, and 24 and adult), and apoptosis was quantitated by terminal deoxynucleotide transferase-mediated dUTP nick end labeling and cleaved caspase-3 immunoreactivity. Compared with the euthyroid, primary somatosensory cortex (S1) in the hypothyroid group exhibited enhanced apoptosis. In S1 of euthyroid rats, apoptotic cells were mostly found in cortical layers I-III and the proportion of apoptotic cells enhanced significantly in the hypothyroid group (P < 0.001). Most of the apoptotic cells were neurons, as assessed by double immunolabeling. A significantly increased activation of caspase-3 and -7, decreased levels of antiapoptotic proteins Bcl-2 and Bcl-x(L), and increased levels of proapoptotic protein Bax was observed in the developing cerebral cortex of hypothyroid rats, compared with the euthyroid (P < 0.001). In addition, hypothyroidism significantly elevated the levels of 53-kDa pro-nerve growth factor (P < 0.001) and p75 neurotrophin receptor (P < 0.001) and decreased TrkA expression. Taken together, we provide evidence for the possible contribution of pro-nerve growth factor/p75 neurotrophin receptor pathway in hypothyroidism-enhanced apoptosis during rat cortical development. Thus, the present study may help in explaining the mechanism of the deleterious effect of thyroid hormone deficiency on cerebral cortex development in children.

Undetectable serum IgA and low IgM concentration in children with congenital hypothyroidism

Some studies suggest thyroid hormones may regulate the human immune system. In order to evaluate the effect of thyroid hormone deficiency on antibody production, we evaluated serum IgA and IgM concentrations in 83 children with congenital hypothyroidism (CH), diagnosed by neonatal screening. Patients were compared to two healthy, age-matched control groups. Patients with permanent CH had a significantly higher frequency of undetectable IgA concentrations (thyroid agenesis, P < 10 −5; thyroid ectopy, P = 0.013) and lower concentrations of IgA (thyroid agenesis, P < 10 −6; thyroid ectopy, P < 10 −5; dyshormonogenesis, P = 0.0002) and IgM (thyroid agenesis, P = 0.0002; thyroid ectopy, P < 10 −6; dyshormonogenesis, P = 0.0017) compared to control group. No difference was observed between patients with transient hypothyroidism and controls. A significant correlation was observed between serum IgA and IgM concentrations and fT 4 levels. IgA and IgM deficiency is correlated with the severity of congenital hypothyroidism and may help to evaluate the duration and severity of thyroid hormone deficiency during prenatal life.

The role of thyroid hormone in fetal and neonatal brain development

To understand how thyroid hormone regulates brain development it is important to identify thyroid hormone-responsive brain genes; determine how regulated expression of these genes affects brain cell development, physiology, and function; and determine how these physiologic changes affect brain function. The authors summarize recent studies contributing to the understanding of these processes and discuss important new studies that assess thyroid hormone metabolism in the developing brain. Specific thyroid hormone transporters are expressed in the developing brain. Recent data suggest that regulated expression of these transporters may control brain thyroid hormone influx and efflux. Additional data support a role for deiodinases in controlling local iodothyronine concentrations in the developing brain. A series of recent reports assesses the role of thyroid hormone in oligodendrocyte development and axonal myelination. These data provide a cellular and molecular explanation for the hypomyelination observed in neonates that have developed in a hypothyroid state. The cerebellar Purkinje cell is another well-described target of thyroid hormone in the developing brain. A recent study provides evidence that thyroid hormone acts directly on the Purkinje cell to regulate dendritic arborization. Finally, important new data provide insight regarding the functional effects of thyroid hormone deficiency on neuronal activity. Recent work has provided exciting new insights regarding the mechanisms controlling thyroid hormone action in the developing brain. It seems likely that regulation of thyroid hormone metabolism and transport during brain development is a critically important mechanism of control. Additionally, important new findings have furthered our understanding of the structural and physiologic effects of thyroid hormone deficiency and excess on brain cell function.

Developmental delay and unstable state of the testes in the rdw rat with congenital hypothyroidism.

From the present study of the rdw rat, it is clear that the thyroid hormone is essential for the development and maintenance of the testes. In previous studies, the thyroid hormone has few serious effects on the testes except during the neonatal stage when the thyroid hormone receptor is mainly present. However, there is little knowledge concerning the prolonged effect of thyroid hormone deficiency throughout the rat's life span. In the present study, a morphological analysis was performed on the testes of rdw rats with congenital hypothyroidism. The rdw testes required a longer time to develop into the normal adult structure. Moreover, the developed, normal structure began to degenerate after full maturation. Specific characteristics of the rdw testes include: (i) a prolonged proliferation of Sertoli cells during postnatal development; (ii) a developmental delay in the appearance of spermatocytes and spermatid; (iii) direct contact with each other for both spermatocytes and spermatids, without Sertoli cell cytoplasm completely intervening between adjacent germ cells; (iv) subsequent apoptosis of germ cells after maturation; (v) reduction in the height of the seminiferous epithelium; and (vi) lower testosterone levels in the rdw rats, especially during old age. Thus, we conclude that the thyroid hormone plays an important role in developing and maintaining normal function of testes.

Effects of thyroid hormone deficiency on behavior in rat strains with different predisposition to catalepsy

The effects of thyroidectomy on anxiety-related behavior in the elevated plus-maze test, locomotor activity, and defecation in the open-field test and duration of cataleptic freezing were studied in rats of two strains differing in predisposition to catalepsy: cataleptic strain GC and its ancestor strain Wistar. Total thyroxine level was significantly decreased in control GC rats compared to that in control Wistar rats. Control Wistar and GC rats did not differ either in the percentages of open-arm entries or the time spent therein in the elevated plus-maze test or in defecation score in the open-field test. At the same time, control Wistar rats showed more locomotor activity compared to control GC rats in the open-field test. Thyroid hormone deficiency did not affect the percentages of open-arm entries and the time spent therein in the elevated plus-maze test as well as defecation score in both strains. Thyroidectomy did not alter significantly locomotor activity in Wistar rats, but produced a nearly twofold increase in locomotor activity in GC rats. The most important finding is that thyroidectomy significantly increased the expression of catalepsy in Wistar rats, which points to a role of thyroid hormones in the regulation of predisposition to cataleptic reaction.

Regulation of glucogenesis by thyroid hormones in fetal sheep during late gestation.

The effects of thyroid hormone deficiency in utero on the fetal glucogenic capacity were investigated by measuring glucose production and hepatic levels of glycogen and gluconeogenic enzymes in normal sheep fetuses in the fed and fasted states during late gestation and in those made thyroid hormone deficient by fetal thyroidectomy (TX). In the fed state, fetal TX had no effect on glucose uptake, utilisation or production by the fetus. It also had no apparent effect on the glycogen content or activities of the key gluconeogenic enzymes in the fetal liver. In addition, fetal plasma concentrations of insulin, cortisol, adrenaline or noradrenaline were unaffected by fetal TX in the fed state. In contrast, the rates of fetal O(2) consumption and CO(2) production per kilogram fetal bodyweight were significantly lower in TX than in intact fetuses in the fed state (P<0.05). TX prevented fetal glucose production in response to maternal fasting for 48 h. It also abolished the normal decreases in the fetal glucose carbon oxidation fraction, the rate of CO(2) production from glucose carbon and in the fraction of the umbilical O(2) uptake used for glucose carbon oxidation that occur during fasting in intact fetuses. At the end of the fast, plasma noradrenaline concentrations and hepatic levels of glycogen, glucose 6-phosphatase, fructose diphosphatase and alanine aminotransferase were significantly lower in TX than in intact fetuses. These observations show that thyroid hormones are essential for glucogenesis in the sheep fetus during late gestation and suggest that these hormones act both on the hepatic glucogenic pathways and on the mechanisms activating glucogenesis in utero.