Estradiol distribution and penetration in rat skin after topical application, studied by high resolution autoradiography

Abstract

Transdermal pathways and targets in the skin for estradiol were investigated using dry-mount autoradiography. 3H-estradiol-17 beta was applied at doses of 30.1 pmol, 120.4 pmol and 301 pmol/cm2 to shaved rat skin in the dorsal neck region. Vehicles were DMSO, ethylene glycol or sesame oil. After 2 h of topical treatment with 30.1 pmol 3H-estradiol x cm-2 dissolved in DMSO a distinct cellular distribution was apparent. Target cells with concentrations of radioactivity were found in epidermis, sebaceous glands, dermal papillae of hair and fibroblasts. After treatment with 120.4 and 301 pmol/cm2, a penetration gradient of radioactivity was recognizable however it masked specific cellular and subcellular uptake. The stratum corneum accumulated and retained radioactivity, apparently forming a depot for the hormone. Strong concentration and retention of the hormone was conspicuous in sebaceous glands for more than 24 h, suggesting that sebaceous glands serve as a second storage site for the hormone. In all autoradiograms two penetration pathways to the dermis were visible: one through the stratum corneum and epidermis, the other through the hair canals and hair sheaths.

The Hair Follicle as an Estrogen Target and Source

“…Spelsberg and co-workers (16) were the first to isolate and characterize an estrogen receptor (ER) in human skin in 1980. Furthermore, a reservoir function of the skin for steroids was proposed, because titrated estradiol was retained in the sebaceous glands and the stratum corneum for more than 24 h, implying two penetration pathways for estrogen to the dermis: one through the stratum corneum, and the other through the hair canal and hair sheaths (17). In addition, more recent studies on the expression of ER␣ and ER␤ using RT-PCR (18) and immunohistochemistry (19) have reported that ER␤ is the predominant receptor in human skin, with strong expression in epidermis, dermal fibroblasts, blood vessels, and hair follicle (19), and human keratinocytes are reported to express both ER␣ and ER␤, possibly including a membrane ER␣ (20).…”

Effect of estrogens on skin aging and the potential role of SERMs

“…Autoradiography following administration of systemic or topical estrogen has demonstrated that radio-labeled estradiol binds to dermal fi broblasts in rat and mouse skin (Stumpf et al 1974;Bidmon et al 1990). More recently, specifi c antibodies have demonstrated ERβ, but not ERα is expressed by dermal fi broblasts in the papillary dermis of human scalp skin in both sexes (Thornton et al 2003), whereas primary cultures of human dermal fi broblasts from female skin have been shown to express both mRNA and protein for ERα and ERβ (Haczynski et al 2002).…”

Reflection contrast microscopy for high resolution detection of3H-estradiol in ultrathin sections of human stratum corneum

“…In the majority of research on localization studies in skin after topical application of a substance, LM autoradiography has been used (e.g., Bidmon et al, 1990;Conte et al, 1992;Rutherford and Black, 1969;Suzuki et al, 1978;Touitou et al, 1988;Zelei et al, 1990). Autoradiographs have been visualized with BFM (Bidmon et al, 1990;Rutherford and Black, 1969;Suzuki et al, 1978;Touitou et al, 1988) and dark-field illumination (Conte et al, 1992;Zelei et al, 1990).…”

“…Autoradiographs have been visualized with BFM (Bidmon et al, 1990;Rutherford and Black, 1969;Suzuki et al, 1978;Touitou et al, 1988) and dark-field illumination (Conte et al, 1992;Zelei et al, 1990). However, both types of illumination have some restrictions (Priestley, 1992).…”