Corticosterone supplementation reduced selective protein kinase C isoform expression in the epidermis of adrenalectomized mice

Previous research in this laboratory demonstrated elevated plasma corticost erone and reduced protein kinase C (PKC) activity and selective isoform exp ression in the epidermis of dietary energy-restricted mice. Because PKC is implicated in skin carcinogenesis and because both energy restriction and g lucocorticoid hormone inhibit skin carcinogenesis, the purpose of the prese nt research was to determine whether the elevated glucocorticoid hormone in the energy-restricted mouse contributed to the changes in PKC protein expr ession, Two strategies were used to control corticosterone in adrenalectomi zed mice: (a) corticosterone-containing pellets were implanted in mice, and a dose response increase in corticosterone was observed with 5-, 10-, and 35-mg corticosterone implants with average peak values of 68 +/- 22 ng/ml ( P < 0.01); and (b) corticosterone was administered in the drinking water, a nd plasma corticosterone was elevated in a dose-dependent manner in mice ki lled at 6:00-6:30 p,m, (P < 0.01; peak values of 300-400 ng/ml). The expres sion of PKC alpha, PKC delta, and PKC is an element of protein were not con sistently altered by corticosterone with the two strategies. PKC eta protei n expression was elevated in the adrenalectomized mice administered 3 or 60 mug of corticosterone/ml in drinking water (P < 0.01). PKC xi protein expr ession was reduced by all doses of corticosterone in the implant or drinkin g water (P < 0.05), and a reduction of 41% was achieved with the mice admin istered 60 mug of corticosterone/ml in drinking water. In mice fed control or energy-restricted diet, with or without adrenalectomy, PKC xi protein wa s reduced in sham-operated, energy-restricted mice in comparison with contr ol diet, sham-operated mice (P < 0.02), whereas PKC xi protein was not sign ificantly different between adrenalectomized control and adrenalectomized, energy-restricted mice. These data indicate that administration of corticos terone in drinking water most closely mimicked the circulating corticostero ne and epidermal PKC changes observed in dietary energy restriction. Elevat ed plasma glucocorticoid levels in the dietary energy-restricted mouse may contribute to the alteration of PKC protein levels in the epidermis.