The Infant & Thyroid Hormones

Baum M, Dwarakanath V, Alpern RJ, Moe OW - "Effects of thyroid hormone on the neonatal renal cortical Na+/H+antiporter" Kidney Int 53(5):1254-8 (1998) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9573540&form=6&db=m&Dopt=r

"... Brush border membrane NHE-3 protein abundance in hypothyroid and hyperthyroid neonates was one-third and twofold that of euthyroid 21-day-old rats, respectively (P < 0.001). These data are consistent with a potential role of thyroid hormone in the postnatal increase in Na+/H+ antiporter activity."

Bonet B, Herrera E - "Maternal hypothyroidism during the first half of gestation compromises normal catabolic adaptations of late gestation in the rat" Endocrinology 129(1):210-6 (1991) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 2055183&form=6&db=m&Dopt=r

• "Results show that maternal hypothyroidism during the first half of gestation impaired the anabolic events occurring during this phase and compromised the normal catabolic response during late gestation even when T4 treatment was restored."

Bonet B, Herrera E - "Different response to maternal hypothyroidism during the first and second half of gestation in the rat" Endocrinology 122(2):450-5(1988) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 3338409&form=6&db=m&Dopt=r

Cao XY, Jiang XM, Dou ZH, Rakeman MA, Zhang ML, O'Donnell K, Ma T, Amette K, DeLong N, DeLong GR - "Timing of vulnerability of the brain to iodine deficiency in endemic cretinism" N Engl J Med 331:1739-44 (1994) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 7984194&form=6&db=m&Dopt=r

• Treatment in the third trimester of pregnancy or after delivery did not improve neurologic status, but head growth and developmental quotients improved slightly. Treatment during the first trimester, which was technically problematic, improved the neurologic outcome. CONCLUSIONS. Up to the end of the second trimester, iodine treatment protects the fetal brain from the effects of iodine deficiency. Treatment later in pregnancy or after delivery may improve brain growth and developmental achievement slightly, but it does not improve neurologic status.

Dean F, Matthews SG - "Maternal dexamethasone treatment in late gestation alters glucocorticoid and mineralocorticoid receptor mRNA in the fetal guinea pig brain" Brain Res 846(2):253-9 (1999) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 10556643&form=6&db=m&Dopt=r

• Development of the fetal hypothalamo-pituitary-adrenocortical (HPA) axis is critical for fetal maturation and responses to stress. Guinea pigs, unlike rats, give birth to mature young, and peak brain growth occurs around days 48-52 (75%) of gestation. There is extensive development of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) systems at the time of rapid brain growth in guinea pigs. Since approximately 10% of pregnant women are treated with synthetic glucocorticoids in late gestation, to promote fetal organ maturation, we tested the hypothesis that fetal exposure to glucocorticoids modifies developing GR and MR systems in the brain. Pregnant guinea pigs were subcutaneously injected with dexamethasone (dex; 1 mg/kg) or vehicle on days 50 and 51 of gestation (term=70 days). On day 52, guinea pigs were killed and the fetuses rapidly removed. Maternal dex treatment resulted in increased plasma cortisol concentrations in female fetuses, but decreased cortisol in male fetuses. Plasma thyroxine levels were increased in both female and male fetuses following maternal dex-treatment. Exposure to dex resulted in significant increases in MR and GR mRNA in the CA1-2 region of the hippocampus, and MR mRNA in the dentate gyrus in female fetuses. There was no effect of dex on GR or MR mRNA in the male fetuses. In conclusion, the effect of synthetic glucocorticoid on the developing brain GR and MR systems is sex-specific and is confined to very specific regions of the hippocampus. Since the hippocampus plays a central role in mediating glucocorticoid negative feedback of HPA function, alterations in the fetal development of corticosteroid receptors may form the basis of permanently modified HPA activity following fetal exposure to endogenous or synthetic glucocorticoid.

de Villard R, Flachaire E, Thoulon JM, Dalery J, Maillet J, Chauvin C, Quincy C, Renaud B  - "Platelet serotonin concentrations in autistic children and members of their families" Encephale 12(4):139-42 (1986) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 3792272&form=6&db=m&Dopt=r

Evans IM, Sinha AK, Pickard MR, Edwards PR, Leonard AJ, Elkins RP - "Maternal hypothyroxinemia disrupts neurotransmitter metabolic enzymes in developing brain." J Endocrinol 161(2):273-9  (1999) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 10320825&form=6&db=m&Dopt=r

Gao B, Yin G - "Effects of high-dose iodine on brain development in mice" Zhonghua Yu Fang Yi Xue Za Zhi 31(3):134-6  (1997) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 9812587&form=6&db=m&Dopt=r

• It is an important topic in medicine and genetics, which has not yet been studied in depth, that whether high-dose iodine, especially iodine excess in mother's body, can cause impediment of brain development in babies as iodine deficiency do. An animal model of goiter was reconstructed in mice with feeding them water containing high level of iodine for three months. Weight of brain, protein and nucleic acid concentrations were measured in one-, seven-, 14-, 21- and 30-day old young mice, and morphological changes in the brain and their abilities of learning and memory were observed in 30-day old young mice, born to mothers with high-iodine goiter. Results indicated that weight of brain, protein content, ratio of protein to DNA, RNA content, and ratio of RNA to DNA all decreased significantly, and DNA content increased in the brain of high-iodine mice, as compared with those in normal iodine mice. Abilities of learning and memory in 30-day old mice decreased. And, those changes began from the seventh to 14th days after their birth. It suggests that excessive intake of iodine, as iodine deficiency, can not only cause high-iodine goiter, but also damage nervous system leading to retardation of brain development and impediment of its function.

 Gilboa N, Swanson JR - "Serum creatine phosphokinase in normal newborns" Arch Dis Child 51(4):283-5 (1976) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 1275541&form=6&db=m&Dopt=r

• "Serum creatine phosphokinase (CPK) activity in 70 normal newborns was found to be significantly higher than the normal values found in adults or older children, and in some cases reached a level up to 10 times normal. It declined to near normal activity during the first 4 days and to normal level of activity by age 6-10 weeks. No clear correlation between birth trauma and increase in serum CPK activity was shown. CPK activity in cord blood was lower than in venous and capillary blood. Because of the increased CPK activity found in normal newborns, screening for Duchenne-type muscular dystrophy should be postponed for a few weeks after delivery."

Glinoer D - "What happens to the normal thyroid during pregnancy?" Thyroid 9(7):631-5 (1999) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 10447005&form=6&db=m&Dopt=r

Glinoer D, De Nayer P, Delange F, Lemone M, Toppet V, Spehl M, Grun JP, Kinthaert J, Lejeune B - "A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects" J Clin Endocrinol Metab 80(1):258-69  (1995) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 7829623&form=6&db=m&Dopt=r

Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, O'Heir CE, Mitchell ML, Hermos RJ, Waisbren SE, Faix JD, Klein RZ - "Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child" N Engl J Med 341(8):549-55 (1999) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 10451459&form=6&db=m&Dopt=r

Hadj-Sahraoui N, Seugnet I, Ghorbel MT, Demeneix B - "Hypothyroidism prolongs mitotic activity in the post-natal mouse brain" Neurosci Lett 280(2):79-82  (2000) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 10686382&form=6&db=m&Dopt=r

• Circulating T(4) and T(3) were measured during the first three post-natal weeks in the mouse and found to increase in a triphasic manner. The first increase occurred at post-natal day 6 and was simultaneous with a decrease in bromodeoxyuridine incorporation in areas showing post-natal mitosis. We investigated whether there was a causal relationship between increased thyroid hormone levels and decreased proliferation by inducing hypothyroidism in dams and progeny. Hypothyroidism prolonged mitotic activity in the olfactory bulb, hippocampus, subventricular zone and the cerebellar cortex. This suggests that the increase in T(3) at the end of the first postnatal week is implicated in terminating progenitor proliferation in many parts of the mouse brain.

Hetzel BS, Mano MT -"A review of experimental studies of iodine deficiency during fetal development" J Nutr 119:145-51(1989) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 2493080&form=6&db=m&Dopt=r

Janson A, Rawet H, Perbeck L, Marcus C - "Presence of thyrotropin receptor in infant adipocytes" Pediatr Res 43(4 Pt 1):555-8  (1998) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 9545014&form=6&db=m&Dopt=r

Kirby JD, Jetton AE, Cooke PS, Hess RA, Bunick D, Ackland JF, Turek FW, Schwartz NB - "Developmental hormonal profiles accompanying the neonatal hypothyroidism-induced increase in adult testicular size and sperm production in the rat" Endocrinology 131(2):559-65 (1992) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 1639007&form=6&db=m&Dopt=r

• "Neonatal treatment with the reversible goitrogen 6-N-propyl-2-thiouracil (PTU) results in a near doubling of testicular size and a 25% increase in the efficiency of spermatogenesis, without affecting circulating testosterone (T) levels in adult rats. The objectives of the present study were to examine the effects of neonatal PTU treatment on the pattern of testicular growth and circulating levels of anterior pituitary (FSH, LH, PRL, GH, and TSH), gonadal [immunoreactive inhibin-alpha (irI alpha) and T], and thyroid (T3 and T4) hormones over the first 100 days of life. Treatment of rats with PTU from birth to 24 days of age significantly reduced testicular weights between 10 and 60 days of age. However, the duration of testicular growth was extended in treated males, resulting in a 68% increase at 100 days of age. Serum gonadotropin levels in treated males were reduced throughout the experimental period, typically remaining between 50-70% of control levels. The characteristic robust prepubertal FSH peak was absent in PTU-treated males. Initially high until 20 days of age, irI alpha levels characteristically declined to adult levels (200-300 pg/ml) in control males. In treated males, irI alpha levels were reduced during the period of hypothyroidism, increased between 30 and 60 days, and then declined, but remained significantly higher (1.7- to 2-fold greater) than those observed in control males. Serum T levels were similar in treated and control males. Control males demonstrated increased T levels beginning at 45 days of age, earlier than observed in treated males; however, similar peak T levels were observed in all males. PTU treatment significantly suppressed serum GH and PRL and led to a 14-fold increase in circulating TSH during the period of treatment. However, unlike the gonadotropins, these hormones returned to control levels after PTU treatment, suggesting that the reduced levels of FSH and LH observed are not due to a generalized reduction in pituitary function. Serum T4 and T3 levels returned to control levels within 15 days after the removal of PTU. These results demonstrate that the neonatal PTU treatment-induced increases in adult testicular size and sperm production were not due to increased levels of FSH at any point in development. On the contrary, the observed increases occur in spite of chronically reduced FSH levels.

Klein RZ, Haddow JE, Faix JD, Brown RS, Hermos RJ, Pulkkinen A, Mitchell ML - "Prevalence of thyroid deficiency in pregnant women" Clin Endocrinol (Oxf) 35(1):41-6 (1991) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 1889138&form=6&db=m&Dopt=r

• OBJECTIVE: The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring. DESIGN: TSH concentrations were measured in the sera of women at 15-18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest in order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyroid antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and/or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women. PATIENTS: The sera were from 2000 consecutive women in Maine being tested for alpha-fetoprotein concentration at 15-18 weeks of gestation. RESULTS: TSH concentrations above 6 mU/l were found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9-54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty-eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls. CONCLUSIONS: Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data indicate a sufficiently high prevalence of thyroid dysfunction to demand investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy.

Kumar R, Chaudhuri BN - "Altered maternal thyroid function: fetal and neonatal development of rat" Indian J Physiol Pharmacol 33(4):233-8 (1989) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 2620965&form=6&db=m&Dopt=r

• Plasma thyroxine was not measurable in fetus from hypothyroid mothers till 21st day of gestation.

Manning JT, Bundred PE - "The ratio of 2nd to 4th digit length: a new predictor of disease predisposition?" Med Hypotheses 54(5):855-7 (2000) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 10859702&form=6&db=m&Dopt=r

• The ratio between the length of the 2nd and 4th digits is: (a) fixed in utero; (b) lower in men than in women; (c) negatively related to testosterone and sperm counts; and (d) positively related to oestrogen concentrations. Prenatal levels of testosterone and oestrogen have been implicated in infertility, autism, dyslexia, migraine, stammering, immune dysfunction, myocardial infarction and breast cancer. We suggest that 2D:4D ratio is predictive of these diseases and may be used in diagnosis, prognosis and in early life-style interventions which may delay the onset of disease or facilitate its early detection.

Marcus C, Ehren H, Bolme P, Arner P - "Regulation of lipolysis during the neonatal period. Importance of thyrotropin" J Clin Invest 82(5):1793-7  (1988) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 3183066&form=6&db=m&Dopt=r

Martinez-Galan JR, Pedraza P, Santacana M, Escobar del Ray F, Morreale de Escobar G, Ruiz-Marcos A - "Early effects of iodine deficiency on radial glial cells of the hippocampus of the rat fetus. A model of neurological cretinism" J Clin Invest 99(11):2701-9 (1997) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 9169500&form=6&db=m&Dopt=r

• The most severe brain damage associated with thyroid dysfunction during development is observed in neurological cretins from areas with marked iodine deficiency. The damage is irreversible by birth and related to maternal hypothyroxinemia before mid gestation. However, direct evidence of this etiopathogenic mechanism is lacking. Rats were fed diets with a very low iodine content (LID), or LID supplemented with KI. Other rats were fed the breeding diet with a normal iodine content plus a goitrogen, methimazole (MMI). The concentrations of -thyroxine (T4) and 3,5,3'triiodo--thyronine (T3) were determined in the brain of 21-d-old fetuses. The proportion of radial glial cell fibers expressing nestin and glial fibrillary acidic protein was determined in the CA1 region of the hippocampus. T4 and T3 were decreased in the brain of the LID and MMI fetuses, as compared to their respective controls. The number of immature glial cell fibers, expressing nestin, was not affected, but the proportion of mature glial cell fibers, expressing glial fibrillary acidic protein, was significantly decreased by both LID and MMI treatment of the dams. These results show impaired maturation of cells involved in neuronal migration in the hippocampus, a region known to be affected in cretinism, at a stage of development equivalent to mid gestation in humans. The impairment is related to fetal cerebral thyroid hormone deficiency during a period of development when maternal thyroxinemia is believed to play an important role.

McIntosh GH, Howard DA, Mano MT, Wellby ML, Hetzel BS - "Iodine deficiency and brain development in the rat" Aust J Biol Sci 34(4):427-33  (1981) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 7305758&form=6&db=m&Dopt=r

Morreale de Escobar G, Ruiz de Ona C, Obregon MJ, Escobar del Rey F -"Models of fetal iodine deficiency." In: DeLong GR, Robbins J, Condliffe PG, eds. 'Iodine and the brain' New York: Plenum Press 187-201 (1989)

Mwangi DK - "Effect of propylthiouracil induced hypothyroidism in developing rat cerebellum: comparison of cerebellar parameters in five day old normal and treated rat pups" East Afr Med J 75(10):602-8 (1998) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 10065197&form=6&db=m&Dopt=r

• The effect of pre and postnatal hypothyroid environment on the development of cerebellum in the rat pups was determined. Four groups of rat dams, namely control, Group I, II and III were treated with propylthiouracil (PTU) in water for different length of time during pregnancy and nursing periods. The pups born from these dam groups were subsequently named after the corresponding dam group, namely control, Group I, II and III. General quantitative results showed that pups from the treated dams had significantly lower (p < 0.05) body weights compared to control pups. Cerebella from five day old pups were taken and structural changes estimated using unbiased "design based" stereological methods, which have made it possible to investigate specific qualities in the organ. The total volumes of cerebellum and intracerebellar nuclei were estimated using Cavalieri Principle. The mean total volume of cerebellum and the mean total volume of intracerebellar nuclei were significantly lower (p <0.05) in all the pup groups (I, II, III) from the treated dams compared to control pups from the control dams. The cerebellar volume decreased in relation to the duration of treatment. The mean ratio of the total volume of intracerebellar nuclei to volume of cerebellum was significantly increased (p < 0.05) in Group III pups compared to control and Group I pups. The mean numerical density of neurones in the intracerebellar nuclei was nearly equal in all the pup groups except in Group III pups whereby it was increased. The mean total number of neurones in Groups I and II pups was reduced, but did not reach statistical significance. The mean numerical density of neuroglia in the intracerebellar nuclei was nearly the same in all the pup groups, the mean total number of glial cells was significantly reduced (p < 0.05) in Groups I and II pups compared to control and the mean neuron/glial ratio was increased in Group III pups compared to control and other treated groups. Thus, the neuroglia appear to be more sensitive to hypothyroidism than neurons. The above results show that PTU-induced hypothyroidism causes reduction in structural parameters in developing cerebellum and confirm that growth and maturation of the foetal cerebellum is dependent on the maintenance of normal T4 and T3 levels in the pregnant dam and developing pups during pre and postnatal stages of development.

Oberkotter LV - "Developmental changes in rat thyroid responsiveness to thyrotropin administered by the subcutaneous and peroral route" Proc Soc Exp Biol Med 187(3):360-5 (1988) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 3347611&form=6&db=m&Dopt=r

• "Percentage T4 response (vs basal levels) steadily declined between Days 5 and 15 postpartum, in both sc- and po-bTSH treatment groups. Percentage T3 responsiveness to sc-bTSH also declined between 5 and 12 days postpartum, after which time T3 generation increased. Our results suggest that the neonatal rat is highly responsive to exogenous TSH late in the first week of life, and that the permeability of the gut at this stage of development further facilitates the impact of orally ingested TSH in the suckling."

Paul DA, Leef KH, Stefano JL, Bartoshesky L  - "Low serum thyroxine on initial newborn screening is associated with intraventricular hemorrhage and death in very low birth weight infants." Pediatrics 101(5):903-7  (1998)

Pickard MR, Sinha AK, Ogilvie L, Ekins RP -"The influence of the maternal thyroid hormone environment during pregnancy on the ontogenesis of brain and placental ornithine decarboxylase activity in the rat" J Endocrinol 139(2):205-12 (1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 8308457&form=6&db=m&Dopt=r

Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, Vulsma T, Wiersinga WM, Drexhage HA, Vader HL - "Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy." Clin Endocrinol (Oxf50(2):149-55 (1999)

Potthoff O, Dietzel ID - "Thyroid hormone regulates Na+ currents in cultured hippocampal neurons from postnatal rats" Proc R Soc Lond B Biol Sci 264(1380):367-73 (1997) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 9107052&form=6&db=m&Dopt=r

Rastogi RB, Singhal RL - "The effect of thyroid hormone on serotonergic neurones: depletion of serotonin in discrete brain areas of developing hypothyroid rats" Naunyn Schmiedebergs Arch Pharmacol 304(1):9-13 (1978) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 692746&form=6&db=m&Dopt=r

• 1-day-old rats induced hypothyroidism and decreased the activity of tryptophan hydroxylase in mid-brain region. The levels of 5-hydroxytryptamine also were reduced in cerebellum, mid-brain and striatum by 22%, 29% and 31%, respectively. By contrast, the levels of its metabolite, 5-hydroxyindoleacetic acid, were significantly increased in cerebellum, mid-brain and striatal region. To ascertain whether changes induced by neonatal radiothyroidectomy were specific, the effect of replacement thyroid hormone therapy was studied on 5-hydroxytryptamine metabolism. Daily administration of L-triiodothyronine (10 microgram/100g s.c.) for 25 days beginning from five days after radio-iodine treatment enhanced tryptophan hydroxylase activity, tryptophan and 5-hydroxytryptamine levels to values seen in normal rats of the corresponding age group. The concentration of 5-hydroxyindoleacetic acid decreased following L-triiodothyronine treatment. Furthermore, when replacement therapy with L-triiodothyronine was postponed until adulthood, no significant effects could be seen on various parameters related to 5-hydroxytryptamine metabolism. Our data demonstrate that deficiency of thyroid hormone in early life disrupts the normal upsurge of 5-hydroxytryptamine metabolism in brain. A critical period exists in early life of rats during which thyroid hormone must be present for the optimal development of 5-hydroxytryptamine metabolizing systems in maturing brain.

Schroder-van der Elst JP, van der Heide D, Morreale de Escobar G, Obregon MJ - "Iodothyronine deiodinase activities in fetal rat tissues at several levels of iodine deficiency: a role for the skin in 3,5,3'-triiodothyronine economy?" Endocrinology 139(5):2229-34 (1998) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 9564827&form=6&db=m&Dopt=r

Sinha AK, Pickard MR, Hubank MJ, Ruiz de Elvira MC, Hadjzadeh M, Attree EA, Davey MJ, Rose FD, Ekins RP - "Maternal hypothyroxinemia and brain development: II. Biochemical, metabolic and behavioural correlates" Acta Med Austriaca 19 Suppl 1:49-54 (1992) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 1519452&form=6&db=m&Dopt=r

Thorpe-Beeston JG, Nicolaides KH - "Fetal thyroid function" Fetal Diagn Ther 8(1):60-72 (1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 8452651&form=6&db=m&Dopt=r

• Cordocentesis has permitted the study of fetal thyroid function. In normal pregnancy, fetal blood thyroid-stimulating hormone (TSH), thyroid hormones and thyroid-binding globulin increase with advancing gestation demonstrating functional maturation of the pituitary, thyroid and liver, respectively. The administration of thyroid-releasing hormone to the mother produces a rapid increase in fetal TSH from at least 25 weeks gestation. In hypoxemic growth-retarded fetuses, the concentrations of TSH are higher, and the concentrations of total and free thyroxine are lower than in appropriately grown fetuses. In anemic fetuses from red cell-isoimmunized pregnancies, serum TSH and thyroid hormone concentrations are increased. In some chromosomally abnormal fetuses, particularly those with trisomy 21, TSH is increased.

Vulsma T, Gons MH, de Vijlder JJM -"Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis." NEJM 321:13-6 (1989)

Walters SN, Morell P - "Effects of altered thyroid states on myelinogenesis" Neurochem 36(5):1792-801 (1981) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 7241137&form=6&db=m&Dopt=r

• Myelinogenesis was studied in controls and in rats treated since birth with Methimazole (hypothyroid) or thyroxine (hyperthyroid). The amount of myelin in forebrain and its protein composition were determined between 13 and 40 days of age, the period of most rapid myelin accumulation. Hypothyroid rats had reduced on both and brain weights relative to controls and the yield of myelin was reduced on both a per brain and a per milligram brain protein basis. Developmental changes in the protein composition of isolated myelin followed the pattern of control animals (the percentage of total myelin protein present as proteolipid protein, large basic protein, and small basic protein increased, as did the ratio of proteolipid/large basic protein) but were delayed temporally by 1-2 days. Hyperthyroid rats also had reduced body and brain weights. At 13 days myelin accumulation was greater than that of controls, corresponding to an earlier initiation of myelination. At later ages myelin yield was reduced on a per brain basis but not on a per milligram brain protein basis. The developmental pattern of myelin protein composition was accelerated temporally by 1-2 days. Myelination in optic nerve, assayed by proteolipid protein content, also was slightly delayed in hypothyroid animals and somewhat accelerated in hyperthyroid animals. The relative synthesis of myelin proteins (determined as incorporation of intracranially injected [(3)H]glycine into myelin protein relative to incorporation into whole brain protein), as well as distribution of radioactivity among individual myelin proteins, was determined. The results supported the conclusion of the myelin protein accumulation study; hypothyroidism retards the developmental program for myelinogenesis, whereas in the hyperthyroid state myelin synthesis is initiated earlier but is also terminated earlier.

Yoshimura M, Nishikawa M, Ogasawara H, Horimoto M, Yoshikawa N, Sawaragi I, Inada M - "Measurement of erythrocyte Na,K-ATPase activity in normal pregnant women" Endocr J 40(1):171-7 (1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 7951492&form=6&db=m&Dopt=r

• Serum FT4 levels measured by two different methods were significantly lower in the third trimester than in the first trimester.