Transplacental effects of 3,5-dimethyl-3'-isopropyl-L-thyronine on fetal hypothyroidism in primates
Pregnant Rhesus monkeys treated with 131I at midgestation become hypothyroid and produce fetuses without demonstrable thyroid tissue. In an effort to prevent both maternal and fetal hypothyroidism, we treated 131I-treated pregnant monkeys with 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a thyroid hormone analog with structural changes which facilitate placental transfer. Five pregnant monkeys were treated with 131I (mCi/kg) at 83-87 days of gestation. One week later, three monkeys were started on treatment with DIMIT (10 micrograms kg-1 day-1, im) and two on im L-T4 (2 micrograms kg-1 day-1). Treatment was continued until delivery by Caesarian section at 152-157 days of gestation. None of the DIMIT-treated mothers became clinically hypothyroid, nor did they have elevated serum TSH concentrations despite low serum levels of T3 and T4. T4-treated mothers were also maintained clinically and biochemically euthyroid. At delivery, infants of DIMIT-treated mothers had normal respiratory function and skeletal maturation. Basal and TRH-stimulated TSH concentrations were suppressed in two of the three infants. By contrast, both T4-treated infants resembled untreated cretinous newborns and died soon after delivery from respiratory failure. Serum TSH concentrations were elevated and skeletal maturation was markedly delayed in these animals. We conclude that DIMIT administration to 131I-treated monkeys prevents clinical and biochemical hypothyroidism in the mother and prevents the major clinical manifestations of cretinism in the fetus.
- Research Organization:
- Department of Pediatrics, Hospital for Sick Children, Toronto, Canada
- OSTI ID:
- 5427216
- Journal Information:
- Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 112:6; ISSN ENDOA
- Country of Publication:
- United States
- Language:
- English
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Kinetics
& Toxicology-- Animals
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560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AGE GROUPS
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CARBOXYLIC ACIDS
CHILDREN
DAYS LIVING RADIOISOTOPES
DISEASES
ENDOCRINE DISEASES
ENDOCRINE GLANDS
FETUSES
GLANDS
HORMONES
HYDROXY ACIDS
HYPOTHYROIDISM
INFANTS
INTERMEDIATE MASS NUCLEI
IODINE 131
IODINE ISOTOPES
ISOTOPES
MACACUS
MAMMALS
MONKEYS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANS
PEPTIDE HORMONES
PREGNANCY
PRENATAL EXPOSURE
PRIMATES
RADIOINDUCTION
RADIOISOTOPES
THYROID
THYROID HORMONES
THYRONINE
THYROXINE
TRIIODOTHYRONINE
VERTEBRATES