Triiodothyronine alters the cornification of cultured human keratinocytes

Scaly skin occurs in 80-90% of patients who are hypothyroid, the pathogenesis of which is unknown. Since thyroid hormone (T3) affects growth and differentiation in other organs, we examined the effects of its absence on keratinocytes in vitro. Human neonatal foreskin keratinocytes were cultivated and second passage cells were switched to T3-depleted (-T3) medium at 50% confluence. Cells maintained in the -T3 medium demonstrated increased (1.5 fold) levels of the cross-linking enzyme transglutaminase and increased (1.5 fold) formation of cornified envelopes, when compared to keratinocytes maintained in medium containing physiologic levels (2 x 10^-9 M) of T3. Additionally, in the -T3 cultures, the level of the protease plasminogen activator (PA), an enzyme implicated in the process of shedding of cornified cells, was decreased 70-80% of that measured in +T3 media. Absence of T3 from keratinocyte culture-medium increased both the level of the enzyme responsible for cross-linking cornified envelope precursors and the rate of envelope formation in cultured cells. The decreased levels of PA observed in the -T3 cultures could result in decreased shedding of cornified cells. These alterations in the process of keratinocyte differentiation may explain the clinically observed scaliness associated with hypothyroidism in humans. The molecular mechanism by which T3 alters keratinocyte cornification is not yet known.