Percutaneous Absorption of Estradiol and Progesterone in Normal and Appendage-Free Skin of the Hairless Rat: Lack of Importance of Nutritional Blood Flow

Abstract

Percutaneous absorption occurs after passive diffusion through the different layers of the skin and its appendages. Thereafter, a resorption process into the cutaneous microcirculation brings the compounds into the systemic circulation. The objective of this in vivo study in the hairless rat was to compare the percutaneous absorption of two steroids on normal and appendage-free (scar) skin and to show if differences in absorption result only from the lack of hair follicles and sebaceous glands and/or from a modification of local blood flow. Percutaneous absorption was evaluated with estradiol and progesterone after 30 min, 2 and 6 h. Except after 30 min, the reservoir function of the stratum corneum of scar skin was approximately twice as high as in normal skin. Eighty to ninety percent of the estradiol and progesterone found in the stratum corneum were located in its superficial layers. Inversely, whatever the application time was, the concentrations of both steroids in the epidermis and dermis were significantly higher in normal skin than in scar skin with maximal difference between about 40 and 400 µm, the area of sebaceous gland localization. Cutaneous blood flow in full-thickness skin, assessed by the thallium-201 method, was globally identical in normal and in scar skin. In scar skin, at the level of papillary dermis, a decrease in blood flow due to the thicker viable epidermis and the flat dermoepidermal junction has been shown without implying an accumulation of drug in the epidermis and superficial dermis. Under these conditions, our results clearly demonstrate that the nutritional blood flow does not interfere with the percutaneous absorption of estradiol and progesterone in normal and scar skin. Thus, they confirm the significant contribution of hair follicles and sebaceous glands to drug penetration into the skin and subsequently the systemic circulation.

Investigation of Follicular Penetration of Topically Applied Substances

“…The penetration rate was higher in the case of the skin-containing follicles. Hueber et al [2] confirmed these results comparing the penetration of steroids through follicle-containing rat skin and the skin of newborn rats without any follicles.…”

Oestradiol transmission from males to females in the context of the Bruce and Vandenbergh effects in mice (Mus musculus)

“…radioactivity in the uterus, ovaries, muscle, olfactory bulbs (OB), mesencephalon and diencephalon (MCCDC), and cerebral cortex of inseminated females intranasally administered 10 ml ethanol (control), 10 mCi tritium-labelled oestradiol ( 3 H-E 2 ), 10 mCi tritium-labelled testosterone ( 3 H-T), or 10 mCi tritium-labelled progesterone ( factors including molecular mass, solubility and polarity (Schaefer et al 1982). More specifically, percutaneous absorption has previously been observed for several steroids (Scheuplein et al 1969, Hueber et al 1994, Waddell & O'Leary 2002.…”

Ethnic Variation in Vellus Hair Follicle Size and Distribution

“…The volunteers were all male, aged between 25 and 50 with normal body mass indices (21)(22)(23)(24). All volunteers had previously been informed about the aims and risks of the study and had given their written consent.…”

“…Tenjarla et al [21] and Hueber et al [22,23] found signifi cant differences in percutaneous absorption of appendage-free scarred skin and normal skin. Turner and Guy [24] found signifi cant iontophoretic drug delivery across the skin via follicular structures.…”