Changes in regional keratin polypeptide patterns during phorbol ester-mediated reversible and permanently sustained hyperplasia of mouse epidermis.

The keratin polypeptide pattern of newborn mouse back, ear, and tail epidermis is uniform and consists of eight individual proteins with a molecular weight range of 46,000 to 67,000. In the adult animal, the keratin patterns of the corresponding body sites are both different from the neonatal pattern and different among themselves. Most notably, ear and tail epider mis contains a high-molecular-weight polypeptide (M,, 70,000), which is absent from neonatal and adult back epidermis. This postnatal specialization of the local program of keratin poly peptide synthesis cannot be related to distinct morphological criteria. We have analyzed the behavior of these regional keratinization phenotypes in the adult mouse under the influence of a reversible or a permanently sustained hyperplasia. Both types of epidermal trauma were induced by either single or repeated treatment of skin with tumor-promoting or nonpromoting hyperplasiogens. Independent of the type of hyperplasiogen used, the initial phase of a reversible hyperplasia (0 to 12 hr) is characterized by only marginal morphological alterations, maintenance of the normal one-dimensional keratin pattern, but pronounced changes in the charge properties of distinct keratin polypeptides, indicating disturbances of the secondary phosphorylation-dephosphorylation process. During the acute phase of reversible hyperplasia (1 to 7 days), the local keratinization phenotypes are quantitatively altered due to the en hanced expression of high-molecular-weight keratin polypep tides. However, the charge properties of the newly synthesized proteins appear normal. A comparison of both the sequential morphological alterations during acute hyperplasia and the temporally corresponding changes in the keratin patterns al lows an assignment of the site of synthesis of distinct polypep tides within the epidermis, which is in line with findings of other laboratories. Long-term hyperplasia (2 weeks to 2 months of regular treatment) is not morphologically different from maxi mum reversible hyperplasia. However, it induces both quanti tative and qualitative alterations of the local keratinization phe notypes and causes a reversal of the postnatal divergence of keratin synthesis by generally restoring the neonatal keratin pattern in all three adult epithelia investigated.