The prenatal role of thyroid hormone evidenced by fetomaternal Pit-1 deficiency.
The role of thyroid hormone in the human fetus is uncertain; a significant amount of T4 is transferred from the maternal to the fetal circulation. A mother-infant pair was found to be heterozygotic for a point mutation in codon 271 of the gene encoding Pit-1, a pituitary-specific transcription factor regulating somatotrope, lactotrope, and thyrotrope function. At birth, serum T4 was undetectable in mother and infant. The newborn presented with a striking delay of respiratory, cardiovascular, neurological, and bone maturation. Despite replacement therapy since birth, neurological development of the infant is impaired. Fetomaternal Pit-1 deficiency resulted in unmitigated fetal hypothyroidism that unmasked thyroid hormone as a potent endogenous drive of fetal maturation and revealed placental transfer of maternal T4 as a rescue mechanism for infants with congenital hypothyroidism, preventing fetal and neonatal symptoms of thyroid deficiency and safeguarding developmental potential.
de Zegher
F
F
Department of Pediatrics, University of Leuven, Belgium.
Pernasetti
F
F
Vanhole
C
C
Devlieger
H
H
Van den Berghe
G
G
Martial
J A
JA
D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005333:Fetus / Q000502:physiology*; D005796:Genes; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D017354:Point Mutation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D013902:Radiography, Thoracic; D012886:Skull / Q000000981:diagnostic imaging; D013963:Thyroid Hormones / Q000502:physiology*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C494187:POU1F1 protein, human; D013963:Thyroid Hormones; D050817:Transcription Factor Pit-1; D014157:Transcription Factors