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

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Summary

Transdermal pathways and targets in the skin for estradiol were investigated using dry-mount autoradiography.3H-estradiol-17β 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 pmol3H-estradiol×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 conspicious 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.

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References

  • Allenby AC, Creasey NH, Edington JAG, Fletcher JA, Schock C (1969) Mechanism of action of accelerants on skin penetration. Br J Dermatol 81 [Suppl 4]:47–55

    Google Scholar 

  • Bartek MJ, LaBudde JA, Maibach HI (1972) Skin permeability in vivo: comparison in rat, rabbit, pig and man. J Invest Dermatol 54:114–123

    Google Scholar 

  • Basketter DA (1986) Modulation of EGF receptors during epidermal hyperplasia. In: Marks R, Plewig G (eds) Skin models. Springer, Berlin Heidelberg New York, pp 194–198

    Google Scholar 

  • Blank IH, Scheuplein RJ (1969) Transport into and within the skin. Br J Dermatol 81 [Suppl 4]:4–10

    Google Scholar 

  • Bullough WS (1955) Hormones and mitotic activity. Vitam Horm 13:261–292

    Google Scholar 

  • Butcher EO (1953) Penetration of radioactive stearic acid into the skin of the rat. J Invest Dermatol 21:243–247

    Google Scholar 

  • Chetkowski RJ, Meldrum DR, Steingold KA, Randle D, Lu JK, Eggana P, Hersham JM, Alkaarsig NK, Fletcher AP, Judd HL (1986) Biological effects of transdermal estradiol. N Engl J Med 314:1615–1520

    Google Scholar 

  • De Lignieres B, Basdevant A, Thomas C, Thalabrad JC, Merciar C, Conard J, Guyene TT, Mairon N, Corvol P, Guy-Grand B, Mauvias-Jarvis P, Sitruk-Ware R (1986) Biological effects of estradiol-17β in postmenopausal women: oral versus percutaneous administration. J Clin Endocrinol Metab 62:536–541

    Google Scholar 

  • Dupuis D, Rougier A, Rouget R, Lotte C (1986) The measurement of stratum corneum reservoir: a simple method to predigt the influence of vehicles on in vivo percutaneous absorption. Br J Dermatol 115:233–238

    Google Scholar 

  • Dupuis D, Rougier A, Rouget R, Lotte C, Kalopissis G (1984) In vivo relationship between horny layer reservoir effect and percutaneous absorption in human and rat. J Invest Dermatol 82:353–356

    Google Scholar 

  • Eppenberger U, Hsia SL (1972) Binding of steroid hormones by the 105,000×g supernatant fraction from homogenates of rat skin and variations during the hair cycle. J Biol Chem 247:5463–5469

    Google Scholar 

  • Feiwel M (1969) Percutaneous absorption of topical steroids in children. Br J Dermatol 81 [Suppl 4]:113–116

    Google Scholar 

  • Feldmann RJ, Maibach HI (1965) Penetration of14C hydrocortisone through normal skin: the effect of stripping and occlusion. Arch Dermat 91:661–666

    Google Scholar 

  • Feldmann RJ, Maibach HI (1967) Regional variation in percutaneous penetration of14C cortisol in man. J Invest Dermatol 48:181–183

    Google Scholar 

  • Feldmann HJ, Maibach HI (1969) Percutaneous penetration of steroids in man. J Invest Dermatol 52:89–94

    Google Scholar 

  • Hooker CW, Pfeiffer CA (1943) Effects of sex hormones upon body growth, skin, hair and sebaceous glands in the rat. Endocrinology 32:69–76

    Google Scholar 

  • MacKee GM, Sulzberger MB, Herrmann F, Baer RL (1945) Histological studies on percutaneous penetration with special reference to the effect of vehicles. J Invest Dermatol 6:43–61

    Google Scholar 

  • Maibach HI, Feldmann RJ (1967) The effect of DMSO on percutaneous penetration of hydrocortisone and testosterone in man. Ann N Y Acad Sci 141:423–427

    Google Scholar 

  • Malkinson FD, Ferguson EH (1955) Percutaneous absorption of hydrocortisone-4-C14 in two human subjects. J Invest Dermatol 25:281–283

    Google Scholar 

  • Marty JP, James M, Hajo N, Wepierre J (1980) Percutaneous absorption of oestradiol and progesterone: pharmacokinetic studies. In: Mauvais-Jarvis P, Vickers CFH, Wepierre J (eds) Percutaneous absorption of steroids. Academic Press, New York, pp 205–218

    Google Scholar 

  • Mier PD, Cotton DWK (eds) (1976) The molecular biology of skin. Blackwell, Oxford London, pp 32–199

    Google Scholar 

  • Montes LF, Day JL, Wand CJ, Kennedy L (1967) Ultrastructural changes in the horny layer following local application of dimethylsulfoxide. J Invest Dermatol 48:184–196

    Google Scholar 

  • Munro DD (1969) The relationship between percutaneous absorption and stratum corneum retention. Br J Dermatol 81 [Suppl 4]:92–97

    Google Scholar 

  • Nunez E, Benassayag C, Engelmann F, Jayle MF (1970) Mise en evidence dans un homogenat de peau de ratte d'une fraction proteique fixant l'oestradiol-17β. Bull Soc Chim Biol 52:1341–1349

    Google Scholar 

  • Nunez E-A, Benassayag C, Engelmann F, Jayle M-F (1971) Etude du transfert a travers la membrane cutanee des hormones steroides chez la rate immature. Ann Dermatol Syphiligraphie (Paris) 98:281–327

    Google Scholar 

  • Rutherford T, Black JG (1969) The use of autoradiography to study the localization of germicides in skin. Br J Dermatol [Suppl 4]:75–87

    Google Scholar 

  • Sarkany I, Hadgraft JW (1969) The influence of formulation on topical corticosteroid activity. Br J Dermatol 81 [Suppl 4]:98–102

    Google Scholar 

  • Schenkel L, Barlier D, Riera M, Barner A (1986) Transdermal absorption of estradiol from different body sites is comparable. J Contr Release 4:195–201

    Google Scholar 

  • Scheuplein RJ (1967) Mechanism of percutaneous absorption II. J Invest Dermatol 48:79–88

    Google Scholar 

  • Scheuplein RJ, Blank IH, Brauner GJ, MacFarlane DJ: Percutaneous absorption of steroids. J Invest Dermatol 52:63–70

  • Shaw JE, Mitchell C (1984) Dermal drug delivery systems: a review. J Toxicol-Cutis Ocular Toxicol 2:249–266

    Google Scholar 

  • Shaw JE, Prevo MA, Amkraut AA (1987) Testing of controlled-release transdermal dosage forms. Arch Dermatol 123:1548–1556

    Google Scholar 

  • Stoughton RB (1965) Dimethylsulfoxide (DMSO) induction of a steroid reservoir in human skin. Arch Dermatol 91:657–660

    Google Scholar 

  • Stumpf WE (1976) Techniques for the autoradiography of diffusible compounds. In: Prescott DM (ed) Methods in cell biology, vol. XIII. Academic Press, New York, pp 171–193

    Google Scholar 

  • Stumpf WE, Sar M, Joshi SG (1974) Estrogen target cells in the skin. Experientia 30:196–198

    Google Scholar 

  • Stumpf WE, Clark SA, Sar M, DeLuca HF (1984) Topographical and developmental studies on target sites of 1,25 (OH)2 vitamin D3 in skin. Cell Tissue Res 238:489–496

    Google Scholar 

  • Vickers CFH (1963) Existence of reservoir in the stratum corneum. Arch Dermatol 88:20–23

    Google Scholar 

  • Wendker H, Schaefer H, Zesch A (1976) Penetrations kinetics and distribution of topically applied estrogens. Arch Dermatol Res 256:67–74

    Google Scholar 

  • Wepierre J, Marty J-P (1979) Percutaneous absorption of drugs. TIPS [inauguration issue]:23–26

  • Wheatley VR (1986) Hormonal regulation of sebaceous gland activity. In: Jarrett A (ed) The physiology and pathophysiology of the skin, vol 9. Academic Press, New York, pp 2797–2806

    Google Scholar 

  • Winkelmann RK (1969) The relationship of the structure of the epidermis to percutaneous absorption. Br J Dermatol 81 [Suppl 4]:11–22

    Google Scholar 

  • Witten VH, Ross MS, Oshry E, Hyman AB (1951) Studies of thorium X applied to human skin. J Invest Dermatol 17:311–322

    Google Scholar 

  • Witten VH, Brauer EW, Loevinger R, Holmstrom V (1956) Studies of radioactive phosphorus (P32) applied to human skin. J Invest Dermatol 26:437–447

    Google Scholar 

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This work was supported by US PHS grant NS09914

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Bidmon, H.J., Pitts, J.D., Solomon, H.F. et al. Estradiol distribution and penetration in rat skin after topical application, studied by high resolution autoradiography. Histochemistry 95, 43–54 (1990). https://doi.org/10.1007/BF00737227

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