Lactating PTU Exposure: I-Alters Thyroid-Neural Axis in Neonatal Cerebellum

Abstract

The purpose of this study was to determine the effects of lactating propylthiouracil (PTU) on the thyroid-neural development in newborns. PTU was administered to female rats in drinking water (0.1% w/v) from birth to lactation day (LD) 30. A hypothyroid state was recorded at LDs 20 and 30 in both dams and their offspring where a marked depression (P<0.01) was observed in serum thyroxine (T4) and triiodothyronine (T3) levels, while a reverse pattern was noticed in serum thyrotropin (TSH) level as compared to a control group. Also, the maternal administration caused a highly significant decrease in the level of neonatal growth hormone (GH) at postnatal days (PNDs) 20 and 30. This hypothyroid condition produced inhibitory effects on 5'-monodeiodinase (5'-DI), and on cholinergic enzymes [butyrylcholinesterase (BuchE) and acetylcholinesterase (AchE)] in the neonatal cerebellum at the studied PNDs. This may also delay partially the development of the cerebellar Purkinje cells (PCs) via altering the dendritic morphology at both examined PNDs. All tested parameters in the control group followed a synchronized course of development, and their progress may depend, largely on thyroid state. Thus, PTU may act as a developmental thyroid-neural disruptor, causing dyshormonogenesis and cerebellum dysgenesis.

Keywords: PTU, Thyroid, Cerebellum, Purkinje Cells, Rat Newborns