Neonatal Persistent Exposure to 6‐Propyl‐2‐thiouracil,a Thyroid‐Disrupting Chemical,Differentially Modulates Expression of Hepatic Catalase and C/EBP‐β in Adult Rats

Persistent exposure of rats to 6‐propyl‐2‐thiouracil (PTU) from birth resulted in decreases in plasma thyroid hormone (TH) levels and hepatic expression of catalase and CCAAT enhancer binding protein β (C/EBP‐β). Catalase promoter region (–185 to +52) that contains binding sites for C/EBP‐β showed an augmentation in the methylation level along with a change in methylation pattern of CpG islands in response to PTU treatment. PTU withdrawal on 30 days of birth restored TH levels and C/EBP‐β to control rats in adulthood. Although catalase expression was restored to some extent in adult rats in response to PTU withdrawal, a permanent change in its promoter CpG methylation pattern was recorded. The results suggest that downregulation of adult hepatic catalase gene in response to persistent neonatal PTU exposure may not solely be attributed to thyroid‐disrupting properties of PTU. It is possible that besides thyroid‐disrupting behavior, PTU may impair expression of hepatic catalase by altering methylation pattern of its promoter.     

Regulation of myosin isoenzyme composition in fetal and neonatal rat ventricle by endogenous thyroid hormones

The effect of thyroid hormone on the expression of ventricular isomyosins V1, V2, and V3 was studied in fetal and neonatal rats. Between 15 and 21 days gestation, V3 accounts for 80-90% of fetal ventricular myosin. After birth, there is a rapid transition from the fetal V3 isotype to an equal mixture of V1 and V3 at 3 days, and to 100% V1 at 3 weeks of age. The endogenous serum levels of thyroxine (T4) and triiodothyronine (T3) increase from trace amounts in the fetus to adult levels at 2-3 weeks of age; this increase correlates with the maximal expression of V1 during the same period. Expression of the V1 isomyosin can be eliminated in the neonatal rat if endogenous thyroid hormone synthesis is suppressed by propylthiouracil (PTU) treatment. In the PTU-treated rats, V3 is the only isomyosin synthesized between 1 and 30 days of age. In fetal ventricle, the amount of V1 is also decreased but not completely eliminated by PTU treatment. Conversely, the relative amount of V1 can be increased in the fetal ventricle by increasing the fetal serum concentrations of T4 and T3 to adult physiological levels. In these fetal ventricles, V1 represents greater than 85% of the total myosin. Likewise, the expression and accumulation of V1 could be stimulated in ventricles of PTU-treated, 12-day-old rats by administration of pharmacological or physiological doses of T3. Within 4 to 8 h after an initial dose of T3, V1 accumulates to 5-10% of the ventricular myosin, and by 72 h comprises 60-80% of the myosin. These results indicate that endogenous thyroid hormone induces the synthesis of ventricular heavy chain alpha, which as a dimer forms the V1 isomyosin, or plays a permissive role for the continued synthesis of heavy chain alpha in ventricles of fetal and neonatal rats.     

Investigation of putative control mechanisms for thyroid growth

We have previously shown that the growth response of the rat thyroid to a sustained elevation of the serum level of TSH, induced by goitrogen administration, is self-limiting. This study investigated the possibility that this limitation of growth is due to the inhibitory action of a chalone secreted by the thyroid follicular cells, the serum concentration of which increases as the gland grows. Twenty-seven adult rats were treated with the goitrogen aminotriazole for 5 months to reach a 'plateau of growth'. One group of 9 rats was then subjected to hemithyroidectomy, another to a sham operation, while a third acted as unoperated controls. Four weeks later there was no significant difference between the groups in thyroid weight, follicular cell number or serum TSH. The absence of regeneration following hemithyroidectomy indicates that a systemically-circulating chalone does not play a role in the regulation of growth in the goitrous thyroid. Other mechanisms including the possible role of a 'local' chalone are briefly discussed.     

Complete recovery of growth deficits after reversal of PTU-induced postnatal hypothyroidism in the female rat: a model for catch-up growth

Newborn rats of both sexes were treated from birth with the anti-thyroid goitrogen, n-propylthiouracil (PTU) given in the drinking water of the litter (0.1% w/v). One group received the treatment for 25 days, another for 50 days, and a third group for 120 days. The experimental rats showed growth retardation as well as all other classical signs of developmental arrest or delays induced by postnatal hypothyroidism. In order to assess the ability of the hypothyroid animals to recover spontaneously from the retarded state, at days 25, 50 and 120 postnatal the PTU water was replaced with tap water. In each case, within 5-7 days after PTU withdrawal the animals began to show marked compensatory growth accompanied by many signs of behavioral and physiological recovery. In general, the male rats showed higher compensatory growth rates as compared to the females, enabling them to attain significantly higher body weights. However, when growth recovery was followed for up to 6 months it was found that the male rats were unable to attain complete catch-up growth, regardless of the age at which recovery began, while the females of all age groups were able to achieve this goal. In view of the severity of PTU-induced growth retardation, these results suggest significant plasticity of growth processes in the rat, especially in the female. It is suggested that male and female rats recovering from prolonged PTU-induced growth retardation offer a good model system for the study of biochemical, anatomical and physiological aspects of growth recovery and catch-up growth at both the cellular and organismic levels, particularly in relation to the effects of thyroid, growth hormone, and other growth-promoting factors.     

Ultrastructural detection of the onset of pituitary thyrotroph sensitivity to lowered thyroid hormone concentrations in the fetal sheep

The goitrogen methylthiouracil was administered orally to pregnant ewes of known gestational ages to induce hypothyroidism in both mother and fetus. Developing pituitary thyrotrophic cells were studied using electron microscopy to detect the earliest gestational age at which morphological changes occurred in response to lowered plasma thyroid hormone concentrations. At 50 days of gestation, the pituitaries of fetuses exposed to the goitrogen were indistinguishable from untreated control glands. However, at 58 days and subsequent ages, "thyroidectomy' cells were observed in pituitaries of all hypothyroid fetuses. These findings indicate that fetal sheep pituitary thyrotrophs are sensitive to lowered thyroid hormone concentrations by 58 days of gestation, suggesting that thyroid-thyrotroph interaction exists at this early stage of development.     

丙基硫氧嘧啶影响妊娠合并甲状腺功能亢进孕妇甲状腺功能及妊娠结局的研究

目的:探讨丙基硫氧嘧啶(PTU)影响妊娠合并甲状腺功能亢进(甲亢)孕妇甲状腺功能及妊娠结局的影响。方法:选择我院妇产科2010年3月至2013年1月收治的110例妊娠合并甲亢的患者作为观察对象,随机分为观察组58例,对照组52例。观察组予PTU每天300 mg口服,对照组确诊后未能定期检测甲状腺功能而自行停药,或拒绝PTU药物治疗。结果:观察组TT3、TT4、FT3、FT4、TSH水平均显著低于对照组,差异均具有统计学意义(均P0.05);观察组早产或流产、剖宫产、妊娠高血压、心力衰竭、重度子痫明显低于对照组,而足月产明显高于对照组,差异均具有统计学意义(均P0.05);观察组的围生儿发生胎儿窘迫、低体重儿、新生儿甲亢、转入NICU发生率均显著低于对照组,两组比较差异均具有统计学意义(均P0.05)。结论:规范的PTU治疗能很好地改善妊娠合并甲亢患者的孕期甲状腺功能,减低甲亢对孕妇及新生儿的危害,改善妊娠结局,且对新生儿畸形率无显著的影响,是一种相对安全和有效的治疗方法。     

Inhibitory effect of large doses of propylthiouracil and methimazole on an increase of thyroid radioiodine release in response to thyrotropin.

Thyroidal radioiodine release increased shortly after a single injection of small doses of PTU, while moderate doses of MMI produced a similar increase of thyroidal radioiodine release with a latency of 7-9 hr. Large doses of PTU and MMI failed to augment thyroidal radioiodine release for at least 29 to 34 hr after the initial administration of goitrogens, although plasma TSH increased significantly because of goitrogen administration. An increase of thyroid hormone release in response to exogenous TSH was depressed by PTU and MMI in rats and mice treated with T4. Since this depression of TSH action only continued for a short period in spite of continuous administration of goitrogens, and since final thyroidal radioiodine release rate was similar to that produced by small doses of PTU, the effects mentioned were not simply due to general toxic action of goitrogens. It is suggested that large doses of PTU and MMI not only block thyroid hormone synthesis but also interfere with the action of TSH on thyroid hormone secretion.     

Hypothyroidism in the fetal and neonatal rat does not impair the insulin secretory response to glucose

Fetal and neonatal hypothyroidism was induced by treating pregnant rats with propylthiouracil (PTU) in the drinking water from day 12 of gestation to day 7 postnatally. The serum levels of thyroxine and triiodothyronine were lowered in both mother and offspring and the neonates showed a 20% reduction in weight gain. An i.p. glucose tolerance test on the 7-day old neonates revealed no major disturbances in glucose tolerance or insulin response. The data suggest that thyroid hormones are not essential for the neonatal development of the B-cell secretory response to glucose.     

Effects of thyroidectomy and administration of propylthiouracil (PTU) or thyrotropin (TSH) to pregnant rats on the functional development of the fetal thyroid gland an immunohistochemical study

In order to elucidate the maternal factors influencing the functional development of the fetal rat thyroid gland, pregnant rats were subjected to either thyroidectomy or administration of PTU or TSH and the thyroid glands of the fetuses were examined chronologically by immunohistochemistry to detect thyroglobulin (Tg), T4 and T3. In the group undergoing thyroidectomy, the occurrence of immunoreactive Tg, T4 and T3 was the same as in the control group in spite of slight retardation of the development of the thyroid gland. On the other hand, PTU administration caused remarkable degeneration of the hyperplastic epithelium of the follicles, where immunoreactivity of T4 and T3 was barely detectable, suggesting a transplacental effect of PTU on the fetal thyroid gland. However, Tg remained unaffected and was stained as well as in the controls. Injection of TSH led to a delay in the occurrence of T4 and T3 by one day, probably due to increased levels of thyroid hormone from the stimulated thyroid gland of the mother rats.     

The effect of acute treatment with two goitrogens on plasma thyroid hormones, testosterone and testicular morphology in adult male rats

1. Hypothyroidism was induced in adult male rats by treatment with either iopanoic acid (IOP) or propylthiouracil (PTU). The hypothyroid animals were maintained for a period of 4 weeks. 2. The IOP and PTU treatments produced drastically different thyroid hormone profiles during the treatment period. 3. Serum testosterone levels were not significantly different from controls in either of the goitrogen-treated groups. 4. Testes weights and germ cell populations were not significantly different from controls in either of goitrogen treated groups. 5. Seminiferous tubule morphology showed no significant variation in lumen size or basal lamina structure in either of the treatment groups when compared to the controls.     

Thyroid hormone differentially regulates cellular development in neonatal rat heart and kidney.

The role of thyroid hormone in the control of cardiac and renal cell development was examined in neonatal rats made hyperthyroid by administration of triiodothyronine (T3, 0.1 mg/kg s.c. on postnatal days 1-5) or hypothyroid by administration of propylthiouracil (PTU, 20 mg/kg s.c. given to dams on gestational day 17 through postnatal day 5 and to pups on postnatal days 1-5). Indices of total cell number (total DNA per tissue), cell packing density (DNA per g tissue), and relative cell size (protein/DNA ratio) were evaluated from birth through young adulthood. PTU administration led to primary shortfalls in cell number that were of similar magnitude in both tissues, but persisted somewhat longer in the kidney than in the heart. Deficits in cell packing density and cell size in the hypothyroid animals were secondary to the effect on cell number, displaying smaller magnitudes of effect and a lag in appearance and disappearance of the deficits compared to that for total DNA; indeed, the phase in which tissues were restoring their cell numbers was accompanied by increased cell packing density, reflecting a more rapid restitution of cell numbers than tissue weight or cell size. In contrast to the relatively similar effects of PTU on developing cardiac and renal cells, the effects of T3 were selective for the heart. Although T3 caused general growth impairment, it evoked marked cardiac overgrowth that was accompanied by a striking increase in cell number and a small increase in cell size. The cardiac hyperplasia is unique to the developing animal, as post-replicative heart cells in adult animals show only hypertrophy in response to thyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of increased testis growth and sperm production in adult rats by neonatal administration of the goitrogen propylthiouracil (PTU): the critical period.

We have previously shown that treating rats with the reversible goitrogen 6-propyl-2-thiouracil (PTU) from birth to Day 25 increases testis size and sperm production in adulthood by up to 80% and 140%, respectively. The purpose of this study was to determine the critical period(s) during development when PTU treatment can increase adult testis size and sperm production. Rats were treated with PTU beginning on Days 0, 8, 16, or 24 for periods of 9, 17, or 25 days. To further define the critical period, additional rats were treated with PTU prenatally or on Days 4-24. PTU treatments of 9, 17, or 25 days beginning at birth increased testis weight 18%, 38%, and 69%, respectively, by 135 days of age, while daily sperm production (DSP) increased 35%, 65%, and 94%, respectively. Efficiency of sperm production (DSP/g testis) also increased by approximately 25% in these rats. There was an inverse relationship between testis and body weights: increasing lengths of PTU treatment increased testis weight but decreased body weight. PTU treatment starting on Day 8 or later did not increase testis weight or DSP regardless of duration. Treatment on Days 4-24 increased adult testis weight and DSP similarly to treatment from birth to Day 24, but prenatal PTU treatment was ineffective. Testosterone concentrations were not altered in treated rats, even those with increased testis weight. These results indicate that the later part of the first postnatal week (Days 4-8) is the crucial period during which PTU treatment must begin in order to increase adult testis size and sperm production.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pituitary-thyroid axis reactivity to hyper- and hypothyroidism in the perinatal period: ontogeny of regulation of regulation and long-term programming of responses.

To evaluate the role of perinatal thyroid status in the development of pituitary-thyroid axis regulation, we administered triiodothyronine to newborn rats for the first five days postpartum to achieve hyperthyroidism, or propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5 to achieve hypothyroidism. Plasma T4, T3, and TSH levels were determined from birth through 50 days postpartum. Administration of exogenous T3 produced the expected immediate suppression of plasma T4 and TSH, with recovery toward normal values beginning within days of discontinuing the T3 regimen. Plasma T3 values were markedly elevated during the period in which T3 was being given, but subsequently became subnormal, with deficits persisting into young adulthood. With the PTU regimen, plasma T4 and T3 levels were markedly suppressed through postnatal day 10, rose over the ensuing two weeks, but nevertheless showed significant deficits into adulthood. TSH levels in the immediate neonatal period were subnormal in the PTU group, despite the marked lowering of circulating thyroid hormones; TSH then rose dramatically to levels four times normal, subsiding to control values by the end of the first month. These results suggest that a critical period exists in which regulation of pituitary-thyroid axis function is programmed. During this phase, TSH secretion can be suppressed by excess thyroid hormones, but cannot be increased by hormone deficiencies. Perhaps more importantly, perinatal thyroid status "programs" its own future reactivity, so that early hypothyroidism results in reduced T4 and T3 levels in adulthood, despite normal levels of TSH.     

The effect of mildronate and related substances on levels of thyroid hormones and some intermediates of lipid and carbohydrate metabolism in hyperthyroid and hypothyroid rats

The effects of mildronate [3(2,2,2-trimethylhydrazinium) propionate dihydrate], γ-butyrobetaine (GBB) and their combination (neomildronate) on the level of thyroid hormones and some intermediates of basal metabolism (free fatty acids, triglycerides, glucose) in serum of laboratory rats with various dysfunctions of thyroid glands including idiopathic hyperfunction and also hypofunction induced by administration of 6-propyl-2-thiouracil (PTU) or L-carnitine administration. Intraperitoneal injections of mildronate (150 mg/kg) during 20 days to male Wistar rats with elevated level of thyroid hormones and basal metabolism normalized thyroxin level and parameters of lipid metabolism in serum. Administration of the compounds studied to rats with hypothyroidism induced by administration of PTU or L-carnitine did not influence natural recovery of the hormonal level. Possible biochemical role of these pharmacological treatments is discussed in terms of in regulation of thyroid gland function.     

THYROID PROLIFERATIVE POTENTIAL AS A FUNCTION OF AGE

The effect of a goitrogenic stimulus on thyroid weight and thyroid cell ³HTdR labeling of Sprague-Dawley rats varying from 2 to 40 weeks of age was determined. Propylthiouracil ad libitum in drinking water produced a spurt in follicle cell labeling index and thyroid weight evident after 24 hr for all age groups. The increase in labeling index reached a peak at 5–7 days and then decreased to a level a few times greater than that of the normal unstimulated thyroid. The tritiated thymidine labeling index for thyroid follicle cells and the effect of PTU thereon was determined for August male rats of 3 days to 12 weeks of age. In the older rats, the follicle cell labeling index rose to 5–6% after 4–5 days of PTU treatment and then slowly fell to about 1%, For the unstimulated control rat of comparable age, the labeling index was about 0.1%. At all ages the thyroid showed a rapid response to PTU. Examination of the time sequence of mitotic labeling showed that the DNA synthesis period was 7.5 hr for normal 2-week-old rats and for 10–12-week-old rats that had received PTU for 4 days. There was no second wave of labeled mitoses in either group during the 48-hr interval studied. From the curve of thyroid weight vs time on PTU and from the labeled mitoses curve, inferences regarding the minimum fraction of proliferating follicle cells in the stimulated ‘adult’rat thyroid were made.     

The changes of thyroglobulin in the lysosomal particles of thyroid during the postnatal period in rats.

The distribution of radioactivity and protein-SH groups was studied in neonatal rats injected with 125-I- in the 15,000 g pellets of thyroid glands to obtain information about the colloid which undergoes phagocytosis by lysosomes. The 15,000 g pellet was solubilized in Triton X--100. The soluble portion was enhanced on the 16th day of age, whereas the portion of the insoluble fraction remained almost unchanged. The content of protein-SH groups in the insoluble fraction decreased with age and was increased in the soluble fraction. The concentration of immunoreactive thyroid stimulating hormone (TSH) in the pituitary and in the blood of rats during ontogenesis was higher on the first day after delivery, then decreased within the first seven days and again markedly increased during the third postnatal week. It was concluded that higher amounts of Triton soluble thyroglobulin occurring during the postnatal period in rats reflects the availability of more substrate, i.e. thyroglobulin for pinocytosis and partially depends upon the TSH level. These findings also support the suggestion on maturation of the pituitary-thyroid system during the postnatal period in rats.     

Isoprenaline-induced changes in rat parotid and submandibular glands are age- and dosage-dependent.

Neonatal rats treated with chronic injections of isoprenaline (isoproterenol) for 10 days revealed differential induction of proline-rich proteins and glycoprotein synthesis between the parotid and submandibular glands. Biosynthesis of proline-rich proteins (Mr 17000-35000) and a Mr-220000 glycoprotein were detectable by solubilization in 10%-trichloroacetic acid extracts from parotid glands 14 days after birth. The enzyme lactose synthase (UDP-galactose: 2-acetamido-2-deoxy-D-glucosamine 4 beta-galactosyltransferase) (EC 2.4.1.22) is also induced 4-7-fold in specific activity compared with control neonatal rats, but again only after 14 days post partum, with isoprenaline treatment. This is in accord with the ability of the parotid gland to respond to beta-receptor stimulation and subsequent increases in intracellular cyclic AMP necessary for induction of protein synthesis [Grand, Chong & Ryan (1975) Am. J. Physiol. 228, 608-612]. Induction of the proline-rich proteins and a Mr-190000 glycoprotein in the soluble fraction from the submandibular gland were not detected until 49 days after birth under identical conditions in the same animal. Cyclic AMP in the submandibular gland undergoes increases on beta-receptor stimulation similar to those achieved in the adult animal, 1 day after birth (Grand et al., 1975). This same differential induction between parotid and submandibular gland was obtained with a range of isoprenaline dosages in adult animals. Trichloroacetic acid-soluble proline-rich proteins were isolated from parotid glands at a dosage of 4.0 mg of isoprenaline/kg body wt., but 7.0 mg/kg was required to induce also biosynthesis of these proteins in the submandibular gland. Gland hypertrophy showed the same differential dosage kinetics, based on gland weight, between the two glands; however, hypertrophy could be accomplished at a lower dosage of isoprenaline than that used to induce proline-rich-protein biosynthesis.     

Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone

In the present study the effect of thyroid hormone (T(3)) on oxidative stress parameters of mitochondria of rat liver is reported. Hypothyroidism is induced in male adult rats by giving 0.05% propylthiouracil (PTU) in drinking water for 30 days and in order to know the effect of thyroid hormone, PTU-treated rats were injected with 20 microg T(3)/100 g body weight/day for 3 days. The results of the present study indicate that administration of T(3) to hypothyroid (PTU-treated) rats resulted in significant augmentation of oxidative stress parameters such as thiobarbituric acid reactive substances and protein carbonyl content of mitochondria in comparison to its control and euthyroid rats. The hydrogen peroxide content of the mitochondria of liver increased in hypothyroid rats and was brought to a normal level by T(3) treatment. Induction of hypothyroidism by PTU treatment to rats also resulted in the augmentation of total and CN-sensitive superoxide dismutase (SOD) activities of the mitochondria, which was reduced when hypothyroid rats were challenged with T(3). Although CN-resistant SOD activity of the mitochondria remained unaltered in response to hypothyroidism induced by PTU treatment, its activity decreased when hypothyroid rats were injected with T(3). The catalase activity of the mitochondria decreased significantly by PTU treatment and was restored to normal when PTU-treated rats were given T(3). Total, Se-independent and Se-dependent glutathione peroxidase activities of the mitochondria were increased following PTU treatment and reduced when T(3) was administered to PTU-treated rats. The reduced and oxidised glutathione contents of the mitochondria of liver increased significantly in hypothyroid rats and their level was restored to normal when hypothyroid rats were injected with T(3). The results of the present study suggest that the mitochondrial antioxidant defence system is considerably influenced by the thyroid states of the body.     

Serum thyroid hormones and performance of offspring in ewes receiving propylthiouracil with or without melatonin

Two experiments were conducted during mid-gestation to examine effects in ewes of propylthiouracil (PTU) treatment alone or with melatonin on serum thyroid hormones, postpartum reproduction, and lamb performance. In the first experiment, beginning on day 0 (first day of treatment when all animals were 72.2+/-0.9 days of gestation), ewes received daily treatments (gavage) consisting of either 0mg (n=6) or 40 mg (n=6) PTU/kg body weight/day for 15 days. After 15 days, the 40 mg dosage was decreased to 20mg/kg body weight for an additional 20 days (35 days of PTU). Serum thyroxine (T4) did not differ (P>0.10) between groups through day 4; but on day 5, control females had a serum value of 67 ng/ml compared with 46 (+/-5)ng/ml for PTU-treated ewes (P=0.02). On the last day that 40 mg of PTU was administered, serum T4 averaged 67 and 7 (+/-5)ng/ml (P<0.001) in the two respective groups. Serum T4 remained low and was 80 and 1 ng/ml (P<0.001) in control and treated ewes on day 34. Serum T4 rose gradually after PTU but remained different from that observed in control ewes through day 48. Lambs from control and treated ewes had similar (P=0.46) T4 values at birth but lambs from PTU-treated ewes had lower (P=0.03) birth weights than did those from control ewes. Serum progesterone (P4) after parturition indicated a lack of cyclicity in all ewes. In the second experiment, beginning on day 0 (76.8+/-4.7 days of gestation), ewes received PTU as in Experiment 1. In addition, after 15 days of PTU, melatonin was given (i.m. injections at 5mg/day) for 30 days. Propylthiouracil decreased (P0.60) for lambs born to control and treated ewes. Female offspring of PTU+melatonin-treated dams reached puberty, became anestrus, and returned to cyclicity at similar (P>0.10) times to contemporary ewe lambs. Results indicate that 40/20mg PTU alone or with melatonin does not induce cyclicity after lambing in spring lambing ewes and has little effect on offspring performance.     

Effects of thyroid hormones on the evolution of monoamine oxidase activity in the brain and heart of the developing rat

The evolution of monoamine oxidase (MAO) activity towards tryptamine has been studied from birth to 20 days post-natal in the brain and heart of male rats. Hyperthyroidism was induced by thyroxine injections and hypothyroidism by PTU administration. The results are expressed per unit of fresh weight and per unit of protein weight. Cardiac MAO is higher in the hyperthyroid animals than in controls as soon as 5 days following birth; the difference between the 2 groups increases until 20 days. The deficiency in thyroid hormones, on the other hand, was followed by a slight decrease in the cardiac enzyme, this decrease reflecting the general deficit in protein synthesis. Brain MAO is not affected by hyperthyroidism, but a clear deficit follows PTU administration. This deficit is significant beginning at 10 days and the difference between the 2 groups increases up to 20 days. The effects of PTU-induced hypothyroidism can be corrected by thyroxine injections. Except for the decrease in the level of cardiac enzyme in hypothyroid animals, all the effects on MAO activity are independent of the total protein content of both organs.