Abnormal lipogenesis in thyroid hormone-deficient epidermis

Striking skin changes can accompany hypothyroidism, among them a scaly ichthyosis. The pathogenesis of these disorders is unknown. Since altered sterol metabolism has been associated with other scaling dermatoses, we tested the hypothesis that altered epidermal lipogenesis may accompany hypothyroidism and induce the observed scaling. Thyroidectomized (TX) rats were sacrificed 53 days postthyroidectomy, and the rate of incorporation of the radiolabeled precursor, [14C]acetate, into epidermal lipids was determined. Approximately 2-fold decreases in incorporation of precursor into both polar and neutral lipids were observed in the TX epidermis; the most significant decreases, however, were in the neutral lipids, particularly the sterol and sterol-ester moieties. Total cholesterol pool size was also reduced in the TX epidermis. Similar decreases in sterol biosynthesis were noted in human keratinocytes cultivated in medium devoid of thyroid hormone. These findings demonstrate that lipid metabolism, and notably sterol synthesis, is altered in epidermal keratinocytes deprived of thyroid hormone, and suggest that, as in other scaling disorders, this abnormal sterologenesis may lead to the clinically observed ichthyosis that can accompany hypothyroidism.