Past investigations have established the major events in thyroid system ontogenesis during the fetal-neonatal period in developing mammals. The maturation of neuro-endocrine control and regulatory aspects of thyroid hormone production and the development of tissue responsiveness to thyroid hormones are the last steps in this ontogenesis. The proposed studies employ the fetal and newborn lamb and fetal-neonatal mouse for detailed investigations of these aspects of hypothalamic-pituitary-thyroid system maturation and function during development. We will study the development of neuroendocrine control of hypothalamic thyrotropin releasing hormone (TRH) and pituitary thyrotropin (TSH) secretion; the significance of hypothalamic and extrahypothalamic TRH in fetal metabolism and thyroid development; the maturation of pituitary TRH and triiodothyronine (T3) receptor systems; the ontogenesis of thyroid TSH receptors; the maturation of liver, lung, heart and brain thyroid hormone nuclear receptors, including receptor specificity; the development of liver and kidney mitochondrial T3 receptors; the correlation of thyroid system receptor maturation ad hormone responses; the role of nerve growth factor (NGF) and epidermal growth factor (EGF) in the maturation of hypothalamic-pituitary function; and the interrelationships of thyroid hormones and EGF in skin maturation. The results will help clarify the mechanism(s) of the immaturities on thyroid system function in premature infants as well as the significance of these thyroid dysfunction syndromes, and will provide basic information regarding the timing and the mechanism(s) of thyroid hormone stimulation of growth and development which will be important in the management of hypothyroidism in the fetus and newborn.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD004270-20
Application #
3310256
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1979-06-01
Project End
1989-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
20
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Los Angeles County Harbor-UCLA Medical Center
Department
Type
DUNS #
City
Torrance
State
CA
Country
United States
Zip Code
90509
Wu, Sing-Yung; Polk, Daniel H; Huang, Wen-Sheng et al. (2008) 3'-monoiodothyronine sulfate and Triac sulfate are thyroid hormone metabolites in developing sheep. Pediatr Res 63:149-53
Wu, S Y; Huang, W S; Fisher, D A et al. (2001) 3,3'-Diiodothyronine sulfate excretion in maternal urine reflects fetal thyroid function in sheep. Pediatr Res 50:358-64
Wu, S Y; Polk, D H; Huang, W S et al. (1999) Fetal-to-maternal transfer of 3,3',5-triiodothyronine sulfate and its metabolite in sheep. Am J Physiol 277:E915-9
Wu, S Y; Fisher, D A; Huang, W S et al. (1998) Urinary compound W in pregnant women is a potential marker for fetal thyroid function. Am J Obstet Gynecol 178:886-91
Huang, W S; Kuo, S W; Chen, W L et al. (1996) Increased urinary excretion of sulfated 3,3',5-triiodothyronine in patients with nodular goiters receiving suppressive thyroxine therapy. Thyroid 6:91-6
Wu, S Y; Polk, D; Fisher, D A et al. (1995) Identification of 3,3'-T2S as a fetal thyroid hormone derivative in maternal urine in sheep. Am J Physiol 268:E33-9
Polk, D H; Ikegami, M; Jobe, A H et al. (1995) Postnatal lung function in preterm lambs: effects of a single exposure to betamethasone and thyroid hormones. Am J Obstet Gynecol 172:872-81
Wu, S Y; Polk, D H; Chen, W L et al. (1994) A 3,3'-diiodothyronine sulfate cross-reactive compound in serum from pregnant women. J Clin Endocrinol Metab 78:1505-9
Polk, D H (1994) Diagnosis and management of altered fetal thyroid status. Clin Perinatol 21:647-62
Polk, D H; Reviczky, A; Wu, S Y et al. (1994) Metabolism of sulfoconjugated thyroid hormone derivatives in developing sheep. Am J Physiol 266:E892-6

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