Effect of long-term topical application of dehydroepiandrosterone (DHEA) and oral estrogens on morphology, cell proliferation, procollagen A1 and androgen receptor levels in rat skin

Abstract

Background: After cessation of estrogen secretion by the ovaries at menopause, all estrogens and almost all androgens acting in the skin of postmenopausal women are synthesized locally from dehydroepiandrosterone (DHEA), a prohormone of adrenal origin that progressively declines with age.

Objective: To better understand the effects of DHEA on the skin, ovariectomized (OVX) rats were treated for 9 months with local topical application of DHEA compared with oral conjugated equine estrogens.

Materials and methods: Morphological evaluation, immunohistochemistry for androgen receptor (AR) and Cdc47 proliferation marker, and in situ hybridization for procollagen A1 were performed on dorsal skin.

Results: Local topical DHEA application increased the thickness of the granular cell layer and total epidermis in OVX animals, whereas systemic estrogens had no significant effect. Although DHEA did not affect total dermal thickness, a 190% increase in dermal procollagen A1 mRNA was observed. Moreover, DHEA treatment decreased hypodermal thickness by 47% and increased skin muscle thickness by 58%. In the epidermis, DHEA induced a non-significant increase in cell proliferation, whereas AR labeling was increased in both the epidermis and dermis by DHEA.

Conclusions: Although estrogens did not significantly modify any of the above-mentioned parameters, the androgenic action of DHEA induced significant changes in all skin layers, without any sign of toxicity or lack of tolerance to DHEA after a 9-month local application of 4% (80 mg/kg) DHEA on the skin.