Thyroid hormone deficiency before the onset of hearing causes irreversibledamage to peripheral and central auditory systems

Both a genetic or acquired neonatal thyroid hormone (TH) deficiency may res ult in a profound mental disability that is often accompanied by deafness. The existence of various TH-sensitive periods during inner ear development and general success of delayed, corrective TH treatment was investigated by treating pregnant and lactating rats with the goitrogen methimazole (MMI). We observed that for the establishment of normal hearing ability, maternal TH, before fetal thyroid gland function on estrus days 17-18, is obviously not required. Within a crucial time between the onset of fetal thyroid gla nd function and the onset of hearing at postnatal day 12 (P12), any postpon ement in the rise of TH-plasma levels, as can be brought about by treating lactating mothers with MMI, leads to permanent hearing defects of the adult offspring. The severity of hearing defects that were measured in 3- to 9-m o-old offspring could be increased with each additional day of TH deficienc y during this critical period. Unexpectedly, the active cochlear process, a ssayed by distortion product otoacoustic emissions (DPOAE) measurements, an d speed of auditory brain stem responses, which both until now were not tho ught to be controlled by TH, proved to be TW-dependent processes that were damaged by a delay of TH supply within this critical time. In contrast, no significant differences in the gross morphology and innervation of the orga n of Corti or myelin gene expression in the auditory system, detected as my elin basic protein (MBP) and proteolipid protein (PLP) mRNA using Northern blot approach, were observed when TH supply was delayed for few days. These classical TH-dependent processes, however, were damaged when TH supply was delayed for several weeks. These surprising results may suggest the existe nce of different TH-dependent processes in the auditory system: those that respond to corrective TH supply (e.g., innervation and morphogenesis of the organ of Corti) and those that do not, but require T3 activity during a ve ry tight time window (e.g., active cochlear process, central processes).