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The cellular signalling pathways of a potent 20-epi-22-oxa vitamin D₃ analogue (KH 1060) were examined in vivo in a hairless mouse model. Seventy two hours after a single topical application of KH 1060 a thickening of the epidermis (from 24·8 ±1·2 µm at 0·01 pmol/cm² KH 1060 to 124·2 ± 6 µm at 5 pmol/cm² KH 1060, P<0·001) was elicited due to epidermal hyperproliferation. This effect could be blocked by topical 2·5 µmol/cm sphingosine, an inhibitor of protein kinase C. Two hours after topical application of 2·5 pmol/cm² KH 1060 a translocation of protein kinase C activity from cytoplasm to the membrane fractions was observed. Moreover, using a reverse-transcription polymerase chain reaction technique, a transient upregulation of c-fos gene expression was seen 2 hours after topical treatment with KH 1060. The expression of c-fos was dependent on protein kinase C activation, since after pretreatment with the protein kinase C blocker sphingosine, c-fos messenger RNA was not detected. These findings strongly suggest that KH 1060 stimulates epidermal growth through activation of the protein kinase C - c-fos signalling axis in vivo.

Journal of Endocrinology (1994) 143, 521–525

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