Using transgenic mice with melanocytes in their epidermis (which normal mice do not have), the group had already shown that inducing cyclic AMP production led to significant pigmentation. Further detailed analysis of the melanin expression pathway identified PDE-4D3 as the key regulator of cyclic AMP activity in melanocytes. Topical treatment of the transgenic mice with a PDE-4 inhibitor (rolipram or Ro 20-1724) for five days caused the skin to darken appreciably and the effect could be further enhanced by co-application of forskolin, which stimulates adenylate cyclase activity.
Although PDE4 isoforms play a key role in regulating intracellular cyclic AMP levels in a variety of tissues, the researchers believe that topical application of a selective PDE-4D3 inhibitor has potential to provide safe tanning and reduce the incidence of skin cancer.
The study is published in the journal Genes & Development.