BIOCHEMICAL EFFECTS OF THYROID DEFICIENCY ON THE DEVELOPING BRAIN

Abstract— The effects of neonatal thyroidectomy on some constituents of the cerebrum, cerebellum and liver of the rat have been studied during the first 7 weeks of life. In the normal rat between the 6th and 14th post-natal days the RNA content per unit of DNA in the brain increased by 70 per cent. Although the brain continued to grow from the 14th to the 35th day, the amount of RNA relative to DNA decreased by about 20 per cent. The ratio of protein to DNA increased during the whole period studied and in the cerebral cortex it was more than trebled between the age of 6 and 35 days. The growth of the cerebellum extended over a longer period than that of the cerebrum, its weight increasing by 88 per cent between the ages of 14 and 35 days as compared with a cerebral increase of 34 per cent. The DNA content showed a 50 per cent increase during this period. Qualitatively these maturational changes were not affected by neonatal thyroidectomy. Quantitative changes, which applied equally to the cerebral cortex and brain as a whole, were observed. At the age of 35 days, the weights of the cerebral hemispheres and cerebellum were reduced by thyroidectomy by 20 per cent; the overall DNA content per organ did not change, but the amounts of protein and RNA relative to DNA decreased significantly. It is therefore inferred that thyroid deficiency affects the size of the cells in brain and cerebellum rather than their total number. Conversely, the cell population of the liver was only a quarter of that in the control. There was a small but significant decrease in the hepatic protein and RNA content in the hypothyroid animal. The activities of the following enzymes which served as markers for subcellular fractions in homogenates of cerebral cortex were determined: lactate dehydrogenase for the supernatant, glutamate dehydrogenase for the mitochondrial and glutamate decarboxylase for the synaptosomal fractions. When the activities were expressed on a fresh weight basis a significant decrease by comparison with the control values was observed only in the case of glutamate decarboxylase (—15 per cent at the age of 17–32 days); when the activities were based on DNA content all values were reduced, probably as a result of the general decrease in cell size. Pyrimidine metabolism of brain and liver, studied after the administration of [6-¹⁴C]-orotic acid, was not affected in either tissue by neonatal thyroidectomy. A small but significant reduction in the incorporation of labelled pyrimidine nucleotides in liver RNA was observed, but no significant decrease in the incorporation in cerebral RNA was found in the hypothyroid rats.     

EFFECTS OF CORTICOSTEROIDS ON THE BIOCHEMICAL MATURATION OF RAT BRAIN: POSTNATAL CELL FORMATION

(1) Treatment with cortisol acetate (0.2 mg daily during the first 4 days after birth) reduced the rate of growth in the rat: at 35 days of age the body weight was reduced by 50 per cent and the brain weight, depending on the region, by up to 30 per cent. (2) In the brain the normal increase in cell number was severely inhibited during the period of cortisol treatment; this resulted in a final deficit in cell number of about 20 per cent in the cerebrum and 30 per cent in the cerebellum. (3) To determine whether cortisol affected primarily cell formation or cell destruction the labelling of brain DNA was studied 1 h after a subcutaneous injection of 20 Ci/100 g [2-¹⁴C]thymidine. In the controls the amount of labelled DNA increased by a factor of two in the cerebrum and seven in the cerebellum during the period 2-13 days, and it decreased to 40 and 27 per cent of the peak values in the cerebrum and cerebellum respectively in the following 7 days. The results indicated that mitotic activity is higher in the cerebellum than in the cerebrum in the 2nd week of life. It would appear that in the cerebrum appreciable cell death accompanies new cell formation, especially during the period 13-35 days of age. (4) Cortisol treatment affected cell division rather than cell destruction in the brain since it strongly inhibited the incorporation of [2-¹⁴C]thymidine into DNA. The inhibition was severe during the period of treatment but it did not result in a lasting fall in mitotic activity. At the age of 13 days the amount of labelled DNA formed approached the normal level and it was twice that in controls at 20 days, indicating a tendency for compensating cell deficit by an accelerated mitotic activity. Nevertheless, massive cell proliferation ceased at about the same age as in normals; the labelling of DNA decreased markedly between 13 and 20 days after birth, and the DNA content did not increase after the age of 20 days. (5) In contrast to the marked effect on cell number, cortisol treatment did not influence significantly the maturational changes related to average cell size (DNA concentration) or the chemical composition of cells (RNA/DNA and protein/DNA).     

EFFECTS OF HYPOTHYROIDISM AND UNDERNUTRITION ON DNA CONTENT AND THYMIDINE KINASE ACTIVITY DURING CEREBELLAR DEVELOPMENT IN THE RAT1,2

—The effects of hypothyroidism and several degrees of undernutrition on the development of cerebellar weight, DNA, and thymidine kinase activity were studied in young rats ranging in age from 2 to 22 days. Early propylthiouracil treatment caused a delayed cerebellar cell multiplication. The activity of cerebellar thymidine kinase was suppressed at ages 2 and 5 days and was in excess of control values on days 15 and 22, thus resulting in a delay in the developmental spectrum for thymidine kinase, and extending the time span of activity beyond that of controls. Undernutrition led to varying degrees of reduced cell proliferation at experimental ages 5, 12, and 19 days. Cerebella from the most undernourished animals showed significant differences from controls in thymidine kinase activity at ages 5 and 12 days. Comparisons between sub-groups from within the oversized litters at 5 and 12 days suggested that changes in thymidine kinase activity relate to the degree of undernutrition to which the sub-group is subjected and that during development there may be a critical degree of undernutrition at which a particular essential enzyme becomes affected. This study emphasizes the biochemical similarities and differences between neonatal hypothyroidism and undernutrition, while pointing out the difficulties which exist in biochemical separation of components of the two conditions. Further evidence is presented that thymidine kinase is responsive to hormonal stimuli during cerebellar development and may play an important role in the regulation of DNA biosynthesis in brain as well as other organs.     

Effect of cortisol on the cellular proliferation and maturation in the cerebrum and the cerebellum of the rat: Importance of the age of the animals at the beginning of treatment]

Young rats were given either a single subcutaneous injection (1 mg at 0, 1, 4 or 8 days), or four consecutive daily injections (0.2 mg/day between 0 and 3 days; 0.4 mg/day between 4 and 7 days; 0.6 mg/day between 8 and 11 days) of cortisol acetate in order to test the influence of age on the action of corticosteroids on the biochemical maturation of the cerebrum and cerebellum in terms of their DNA, RNA, and protein contents. The results showed that: 1 The diminution of the DNA content at 35 days was greater in the cerebellum (- 16 to - 32%) than in the cerebrum (- 9 to 20%); the DNA content of the cerebrum was more affected by treatment at birth, whereas that of the cerebellum was more affected by the delayed treatments. Results were different when expressed in terms of reduction of the normal increase: the gain of DNA decreased more in the cerebrum (-70%) than in the cerebellum (-40%); but the most delayed treatment induced a greater effect in both organs. These abnormalities were not always accompanied by a significant decrease of the body weight. 2 Generally, the treatments led to an increase of the mean cell territory, expressed either in terms of decrease of the DNA concentration, or in terms of increase of the organ weight/DNA ratio. Moreover, the increase of the RNA/DNA and the protein/DNA ratios constituted an indication of an accelerated cellular maturation.     

Changes in DNA,RNA, protein and the activities of acid and alkaline DNases in developing and aging rat cerebellum

The content of DNA, RNA and protein in cerebellum at different stages of the life span of rat as well as the ratios of protein to DNA, showed-that in this region extensive cell proliferation occurs between the 1st and 7th day after birth and once again between the ages of 225 and 750 days. The putative DNA degrading enzymes, acid and alkaline DNases, showed a positive correlation with the rapid DNA accretion noticed during developmental stages as well as during old age. From these results, it could be presumed that there was a second bout of glial cell multiplication in aging cerebellum and that DNases must be playing some important role in the process.     

POSTNATAL CHANGES IN FREE AMINO ACID,DNA, RNA AND PROTEIN CONCENTRATIONS OF MINIATURE SWINE BRAIN1

Postnatal developmental characteristics of miniature swine brain were evaluated through the first 9 weeks of age. Differential growth rates of cerebrum, cerebellum and brain stem were defined in terms of DNA, RNA, protein and free amino acid concentrations at ages 5, 21, 35 and 63 days. Within the experimental conditions provided, hyperplasia ceased just prior to ages 21, 35 and 63 days for cerebellum, brain stem and cerebrum, respectively. An additional cerebral growth spurt, observed between weaning at age 35 days and sacrifice at age 63 days, may be indicative of impaired brain development due to inadequate nutrition provided by the dam's milk. Developmental changes in mean concentrations of brain free amino acids varied with anatomical area and differed somewhat from those of other species previously reported. For example, mean cerebral concentrations of aspartic acid, γ-aminobutyric acid and asparagine + glutamine decreased significantly (P < 0·05) with age and mean glutamic acid concentration was 5 times that of taurine.     

Relationship Between the Ubiquitin-Dependent Pathway and Apoptosis in Different Cells of the Central Nervous System: Effect of Thyroid Hormones

We have recently shown that sustained neonatal hyperthyroidism in the rat activates apoptosis of oligodendroglial cells (OLGc) and that inhibition of the proteasome-ubiquitin (Ub) pathway by lactacystin produces increased apoptosis in cerebellar granule cells (CGC). In the present study we have analyzed the relationship between the activation of the Ub-dependent pathway, the expression of the Ub genes and programmed cell death in neurons of the rat cerebellum and cerebral cortex and in OLGc. This study was carried out in normal animals, in rats submitted to sustained neonatal hyperthyroidism and in cell cultures treated with an excess of thyroid hormones. In neurons of the cerebral cortex, thyroid hormone produces an increase of Ub-protein conjugates, an enhancement in the expression of the Ub genes and an increase in apoptosis, while the opposite results are obtained in CGC. These results indicate that in neurons, the changes in the cell death program produced by thyroid hormone run in parallel with those occurring in the Ub-dependent pathway. In OLGc, thyroid hormone increases apoptosis but does not produce changes in the Ub pathway. Preliminary studies indicate that in coincidence with what occurs in optic nerves, the sciatic nerves both in controls and in hyperthyroid animals are unable to form Ub-protein conjugates. These results indicate that in cells of the CNS such as neurons, in which the Ub-dependent pathway is actively expressed, it appears to be closely correlated with apoptosis.     

EFFECT OF UNDERNUTRITION ON CELL FORMATION IN THE RAT BRAIN

Abstract— Rats were undernourished by approximately halving the normal food given from the 6th day of gestation throughout lactation. Growth of the foetuses was nearly normal, in marked contrast to the severe retardation caused by undernutrition during the suckling period. In comparison with controls the size and the DNA content of the brain were permanently reduced by undernutrition during the suckling period: this effect was relatively small, approx. 15 per cent decrease at 21 and 35 days. The rate of ¹⁴C incorporation into brain DNA at 30 min after administration of [2-¹⁴C] thymidine was taken as an index of mitotic activity; compared with controls there was severe reduction in mitotic activity (maximal decrease by about 80 per cent at 6 days in the cerebrum and by 70 per cent at 10 days in the cerebellum). The rate of acquisition of cells was calculated from the slopes of the logistic curves fitted to the estimated DNA contents. In normal animals the maximal slope was attained at 2·7 days and at 12·8 days after birth in cerebrum and cerebellum respectively; the daily acquisition of cells at these times was 4·8 × 10⁶ and 18 × 10⁶ cells respectively. The fractional increase in cell number at the maximum was 5·4 percent per day in the cerebrum and 15·2 per cent per day in the cerebellum. The rate of acquisition of cells relative to the rate of mitotic activity was higher in the brains of undernourished animals than in controls. One of the compensatory mechanisms for the severe depression of mitotic activity in the brain of undernourished animals Seems to involve a reduction in the normal rate of cell loss.     

Thyroid hormones modulate ornithine decarboxylase in the immature rat cerebellum

In this study, we measured ornithine decarboxylase (ODC) activity as a potential parameter to evaluate the response of the developing rat brain to thyroid hormones. In cerebellum, neonatal hyperthyroidism (40 micrograms thyroxine/100 g body weight daily from birth) increased ODC activity at 2 and 5 days of age and then accelerated its developmental decline. Conversely, ODC activity was decreased in 2- and 5-day-old hypothyroid rats (propylthiouracil to the mother), but it was not significantly different from normal thereafter. No significant differences were observed in the forebrain following either treatment. In hypothyroid rat cerebellum, a single injection of triiodothyronine (T3, 100 micrograms/100 g 18 h before sacrifice) increased significantly ODC activity at all ages. A dose-response study showed that 0.5 micrograms T3/100 g is sufficient to obtain maximal stimulation. Finally, administration of antiserum against rat growth hormone had no significant effect on ODC response to T3. These results show that ODC is a useful marker of thyroid state and tissue response in the neonatal rat cerebellum.     

EVOLUTION DE L''INCORPORATION IN VIVO DE L''ACIDE [14C]OROTIQUE DANS L''ARN ET L''ADN DU CERVELET DE JEUNES RATS HYPO- ET HYPERTHYROIDIENS: EFFETS COMPARATIFS DE L''HYPO- ET L''HYPERTHYROIDIE SUR LES MULTIPLICATIONS CELLULAIRES

The change in the body and cerebellar weights, together with the quantity of RNA, DNA and proteins in the cerebellum were studied for the first 10 days and on the 12th, 14th, and 17th days of postnatal life in normal, hypo- and hyperthyroid rats. In the normal animals: (1) The average cellular protein content decreases from the first to the second day, increases to a maximum at 4 days, then decreases. (2) The specific radioactivity of the RNA, 14 h after an intravenous injection of [6-¹⁴C]orotic acid, varies distinctly from birth to 9 days and reaches two maxima at 4 and 6 days. After 9 days it decreases markedly. (3) Mitotic activity (number of replicating cells) increases, reaches a maximum at 9 days, then decreases. (4) The specific radioactivity of the DNA (used as a measure of the percentage of the cellular population in division) reaches a maximum at 6 days. (5) Mitotic efficiency (number of replicating cells in mitotic activity) decreases from 2 to 7 days, and subsequently increases. In the hypothyroid animals: (1) The average cellular protein content increases from the first to the second day and then decreases. (2) The specific radioactivity of the RNA, always significantly higher than that of normal animals, varies from birth to 9 days, reaches two maxima at 4 and 6 days, then decreases after 9 days. (3) Mitotic activity, always significantly lower than that of normal animals, increases from birth, reaches a maximum at 9 days, then decreases. (4) The specific radioactivity of the DNA reaches a maximum at 6 days and the mitotic efficiency a minimum at 7 days. Neither are significantly different from that of normal animals. In the hyperthyroid animals: (1) The average cellular protein content, is maximal at 2 days, then decreases. (2) The specific radioactivity of the RNA, always significantly lower from that of normal animals, decreases from birth. (3) Mitotic activity is similar to that of normal animals, increases from birth up to 6 days, then decreases. (4) The specific radioactivity of the DNA increases from birth up to 5 days, then decreases. It is significantly lower than that of normal animals. (5) Mitotic efficiency is significantly higher than that of normal animals. In the different groups, the maximum of the average cell size, always precedes the maximum of the cellular division. In the hypothyroid animals, the rate of cell death is higher than that of normal animals, and the average cell size is higher during the first fourteen days. In the hyperthyroid animals, the rate of cell death is lower than that of normal animals, and the average cell size is higher at 14 and 17 days.     

Perinatal methadone exposure and brain development: a biochemical study

Abstract— The neurochemical effect of maternally administered methadone (5 mg/kg, DL-methadone-HCI) on the brain (including the olfactory bulbs, cerebellum, and brain stem) and cerebellum of offspring exposed during gestation and/or lactation was studied in 10-, 21-, and 60-day old rats. Brain weights were significantly reduced in all methadone-exposed groups at 10 days of age, while only those rats subjected to methadone during gestation or lactation had deficits in brain weights at day 21; no differences were found at 60 days. Brain DNA content was significantly reduced in all opiate-exposed offspring at every age examined, but RNA/DNA and protein/DNA ratios were only consistently increased in rats of the gestation group. Cerebellar weight was reduced at 10 days in the gestation-lactation pups, at 21 days in rats of the gestation and lactation groups, and at 60 days in animals of the gestation and gestation-lactation groups. Cerebellar DNA content was significantly decreased in pups of the gestation group at every age investigated, but only reduced at 21 days in the lactation group and at 60 days in the gestation-lactation group. Rats in the lactation group had the greatest number of alterations in terms of RNA and protein, with the most noticeable being decreases in mean cellular RNA content on days 21 and 60 and a reduction in the mean cellular protein content on day 60. These data suggest that prenatal and/or postnatal methadone treatment affects the biochemical maturation of the central nervous system; deficits in neurons and/or glia, as well as a reduction in myelination, might be reflected in these changes.     

STIMULATION OF DNA SYNTHESIS BY ISOPROTERENOL IN RAT SUBMANDIBULAR GLAND DURING POSTNATAL GROWTH

The post-natal growth of rat submandibular gland and the effect of isoproterenol on this process were studied. Between 2 and 42 days of age the DNA content of the gland increased linearly but the increase in RNA and protein content was more rapid after 29 days of age. The RNA: DNA and protein: DNA ratio increased linearly with age. The proliferative activity, measured by the incorporation of tritiated thymidine, was maximum in the gland of 7-day-old rats. It declined steadily to a low level in 42-day-old rats. A single injection of isoproterenol had no effect on thymidine incorporation in 2-day-old rats. The drug, however, stimulated DNA synthesis in older animals and the degree of stimulation was inversely correlated with the proliferative activity in control rats. Small doses of isoproterenol given to rats for 4 days between 2 and 5 days of age produced a hypertrophy of the submandibular gland. The same treatment between 7 and 10 days of age caused both hypertrophy and hyperplasia of the gland. It is concluded that both the regulation of growth and the regulation of induced cell proliferation are a function of cellular differentiation and that cell proliferation can be induced only in cells that reached a certain degree of differentiation.     

Effect of hypothyroidism on the labeling of the various RNA species in developing rat brain

The effect of hypothyroidism on the in vitro incorporation of [³H]uridine into different RNA species in tissue slices of rat cerebral hemispheres at 5, 10, 15, and 21 days of age has been investigated. Gel electrophoresis analysis of total, nuclear and microsomal RNA was also accomplished. The results obtained indicate that RNA labeling is differently influenced by hypothyroidism at the various ages examined. RNA labeling is not significantly affected at 5 days of age while at later ages and especially at 21 days it is higher in hypothyroid rats compared to the controls. Moreover distinct differences at the various ages in the transport of newly synthesized RNA from the nucleus to the cytoplasm in the two groups of animals were found. These results are in agreement with the hypothesis that thyroid hormone deficiency causes a delay of the processes of cell proliferation and differentiation in developing rat brain.     

Density-dependent cell division after cortisol treatment of rat thymus in relation to age involution.

Cellular proliferation, in relation to cell density was investigated in the thymus of control and cortisol treated animals at 6 and 18 weeks of age. It was found that there was very little difference in the response of the two age groups to cortisol treatment. Cell density and cellular proliferation were markedly reduced 2 days after cortisol administration. From 4 days there was a rapid increase in cellular proliferation to triple the control rate. The mitotic index remained above normal until 12days then decreased to control values at 14 days. During this time the cell density of the thymus was being progressively restored. At all stages of regeneration, the mitotic index at first increased to a maximum at the mean cell density then decreased at the highest cell concentrations. A model system is discussed to account for this density dependent control of cellular proliferation in the thymus.     

低氧对新生大鼠脾单个核细胞DNA合成及转化的影响

本研究以荧光法测定脾单个核细胞ＤＮＡ合成及ＭＴＴ比色法测定的脾单个核细胞对ＣｏｎＡ的增殖反应,观察模拟高原低氧对出生后１４天大鼠上述两指标的影响,同时也观察了交感神经和副交感神经的活动状态,以初步探讨低氧对上述两指标的作用是如何介导的。结果表明：５ｋｍ海拔高度低氧作用２４ｈ不抑制脾单个细胞ＤＮＡ合成及脾单个核细胞转化,而作用５天时则抑制ＤＮＡ合成及脾单个核细胞转化,分别为对照组的５６．６％（Ｐ＜０．０１）和８６．８％（Ｐ＜０．０５）;７ｋｍ海拔高度低氧作用２４ｈ,ＤＮＡ合成及脾单个核细胞转化均受抑制,分别为对照组的６１．０％（Ｐ＜０．０１）和８１．２％（Ｐ＜０．０１）;７ｋｍ海拔２４ｈ低氧导致脾脏中乙酰胆碱下降,儿茶酚胺升高;用ＤＳＰ－４中枢药理性损毁ＮＥ神经元,可使脾单个核细胞ＤＮＡ合成的抑制程度减弱,脾脏中儿茶酚胺含量下降。这些结果表明低氧可抑制新生大鼠脾单个核细胞的ＤＮＡ合成及转化,并可能与交感神经兴奋及副交感神经抑制有关     

THE EFFECTS OF UNDERNUTRITION ON THE PROTEINS OF OPTIC AND SCIATIC NERVES DURING DEVELOPMENT

Abstract— Polyacrylamide gel electrophoresis has been used to assess the appearance of some optic and sciatic nerve proteins in normal developing rats and in undernourished rats. Of the myelin proteins, the'Wolfgram'proteolipid is already present about the time myelination begins. The basic myelin proteins appear later, first in sciatic and then in optic nerve. A non-myelin basic protein, assumed to be a histone, is present at high levels in both nerves before myelination begins. There is no apparent effect of undernutrition on the appearance and amount of myelin proteins at 12, 16 and 22 days of age. The'histone'protein is reduced in optic and sciatic nerves at times corresponding roughly to the transition periods from cellular proliferation to myelin formation. The possibilities are discussed that myelin basic proteins are synthesized as compact myelin formation occurs, and that there may be retarded cellular proliferation in nerves of undernourished rats.     

Inhibitory influence of thiourea on brain of singi fish (Heteropneustes fossilis bloch) and subsequent recovery by l-triiodothyronine

Immersion of Singi fish in thiourea-containing medium (1 mg/ml) for 45 days significantly decreased the cranio-somatic index, weight of different parts of brain, viz. cerebrum, cerebellum, midbrain and medulla oblongata, and also protein and RNA contents of these different regions. The DNA content of these substructures remained unchanged. In other sets of experiment, thiourea treatment for 33 days caused reduction in mitochondrial cytochrome-linked α-glycerophosphate dehydrogenase (EC 1.1.99.5) activity, and total protein and RNA contents of whole brain, while the amount of mitochondrial protein and total DNA content of whole brain did not undergo significant variation. A single injection of l-triiodothyronine (0.5 μg/g) enhanced this enzyme activity, mitochondrial protein amount and total protein and RNA contents of whole brain of thiourea-treated fish to almost such levels as obtained by l-triiodothyronine injection in normal (control) Singi fish within 3 days. The CSI in normal fish increased by triiodothyronine injection. In thiourea-treated fish, the reduction of CSI was restored to just control level by triiodothyronine.The results are, therefore, discussed as additional supportive evidence of the responsiveness of fish brain to thyroid hormone.     

Effect of Hypo- and Hyperthyroidism on Hexokinase in the Developing Cerebellum of the Rat

Abstract: Total hexokinase levels (units/g tissue) have been measured during postnatal development of the cerebellum in control, hypothyroid, and hyperthyroid rats. In addition, distribution of hexokinase in the developing cerebellum has been observed with an immunofluorescence method. Hypothyroidism delays the normally observed postnatal increase in total hexokinase activity, whereas hyperthyroidism accelerates the increase. In normal animals, hexokinase levels in maturing Purkinje cells pass through a transient increase, with maximal levels at approximately 8 days postnatally followed by rapid decline to relatively low levels by 12 days; hypothyroidism delays this transient increase and subsequent decline, but hyperthyroidism does not appear to affect markedly the timing of this phenomenon. Cerebellar glomeruli are relatively enriched in hexokinase content, as judged by their intense fluorescence. Hypothyroidism delays the development of intensely stained glomeruli. Hyperthyroidism did not appear to cause precocious increase in numbers of glomeruli but may have increased the rate at which the hexokinase was assimilated by newly formed glomeruli. The effects of hypo- and hyperthyroidism on total cerebellar hexokinase levels are interpreted in terms of the effect of thyroid hormone on the biochemical maturation of synaptic structures rich in hexokinase.     

Thyroxine Injections Do Not Cause Premature Induction of Thymidine Kinase in sg/sg Mice

Severe hyperthyroidism from the time of birth causes a premature induction and termination of thymidine kinase activity in the cerebella of wild-type mice. This leads to elevated enzyme levels at postnatal days 5 and 6, with significantly lower levels by postnatal day 7 (which is actually the time of peak activity in normal animals). In this study, neonatal hyperthyroidism does not have significant effects on postnatal day 5, 6, or 7 enzyme levels in the neurological mutant staggerer. This is consistent with the hypothesis that thyroid hormone exerts its effects via the Purkinje cells, which are reduced in number and grossly stunted in the mutant.     

VARIATIONS AU COURS DES DIX PREMIERS JOURS DE LA VIE POSTNATALE DE L''INCORPORATION IN-VIVO DE LA L-[3H]LEUCINE DANS LES PROTEINES DU CERVELET DU RAT NORMAL, HYPO- ET HYPERTHYROIDIEN

The incorporation of L-[³H]leucine into the proteins of rat cerebellum and cerebrum was measured 30min after an intravenous injection of the labelled amino acid. In normal rats. both RSA and the relative RSA of the proteins of the cerebellum and the cerebrum, varied greatly from one day to another during the first ten days of postnatal life. These variations showed a maximum of both the RSA and the relative RSA of the proteins on the 7th day, and 2 minima on the 3rd and 16th day. In hypothyroid animals, both the RSA and the relative RSA of the proteins of the cerebellum and the cerebrum were generally lower than in normal animals. Both showed a maximum at 7 days and a minimum at 3 days. In hyperthyroid animals, both the RSA and the relative RSA of the proteins of the cerebellum were significantly higher than those of normal animals. Both showed 2 minima at 2 and 5 days. In the hypothyroid animals as in the normal, protein synthesis was higher in the second postnatal week than during the first. On the other hand, in the hyperthyroid animals, protein synthesis was greater during the first postnatal week than during the second. The changes in both the RSA and the relative RSA values of the proteins of the cerebellum are discussed as a function of both growth and cellular proliferation. Hyperthyroidism advances these two processes without changing the period that separates them. On the other hand, hypothyroidism changes this period and causes a change in the development of these processes.