title: Effect of hypothyroxinemia on thyroid hormone responsiveness and action during rat postnatal neocortical development.
abstract: Neurological deficits due to maternal and neonatal hypothyroxinemia under mild-moderate iodine deficiency are a major preventable health problem worldwide. The present study assesses the impact of hypothyroxinemia on postnatal neocortical development and also compares it to the known effects of severe hypothyroidism. Our results strongly suggest that even within elevated circulating triiodothyronine (T3) levels, hypothyroxinemia significantly impairs thyroid hormone responsiveness in developing rat neocortex. The significant compensatory alteration in deiodinase levels with unaltered monocarboxylate transporter 8 (MCT8) and thyroid hormone receptors (TRs), although found to be similar in hypothyroxinemic and hypothyroid condition, is more pronounced under later condition. The resultant downregulation of nuclear myelin binding protein (MBP) and mitochondrial transcripts Cytochrome oxidase III (Cox III) as well as significantly enhanced mitochondrial localization of Bax and reduced Bcl-2 and Bcl-xL accompanied by enhanced release of Cytochrome c and Smac with activation of caspase-3 indicates pronounced apoptosis leading to compromised cellular survival. The similarities of this responsiveness albeit with difference in degree under hypothyroidism and hypothyroxinemic state with adequate availability of T3 are suggestive of an independent role of thyroxine in neocortex development. Taken together, this study brings forth the neurophysiological aspects of hypothyroxinemia and underscores the importance of adequate iodine nutrition along with mandatory thyroxin monitoring during pregnancy and after birth.
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Babu
authors.forename: Rohit Anthony
authors.initials: RA
authors.lastname: Sinha
authors.forename: Vishwa
authors.initials: V
authors.lastname: Mohan
authors.forename: Geeta
authors.initials: G
authors.lastname: Rao
authors.forename: Amit
authors.initials: A
authors.lastname: Pal
authors.forename: Amrita
authors.initials: A
authors.lastname: Pathak
authors.forename: Manish
authors.initials: M
authors.lastname: Singh
authors.forename: Madan M
authors.initials: MM
authors.lastname: Godbole
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D007037:Hypothyroidism / Q000097:blood* / Q000139:chemically induced; D007455:Iodine / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency; D019579:Neocortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000139:chemically induced; D051381:Rats; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D013963:Thyroid Hormones; D007455:Iodine