Summary
Retinoids are known to modulate sebaceous gland activity in humans and animals. The nonpolar arotinoid Ro 15-0778 [(E)-1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-(1-methyl-2-phenylethenyl) naphthalene] does not contain a polar end group and is devoid of the classical retinoid side effects of hypervitaminosis A. The favorable toxicological profile stimulated the evaluation of this arotinoid in animal models of sebum production. In castrated, testosterone-stimulated male rats, Ro 15-0778 is 50 times more potent than 13-cis-retinoic acid in inhibiting the production and subsequent secretion of sebum. The oral ED50 value of Ro 15-0778 is 30μg/kg, while an oral dose of 0.5 mg/kg inhibited sebum secretion nearly 1005. In testosterone-stimulated female rats, Ro 15-0778 inhibits sebum secretion significantly with an oral ED50 of 140 μg/kg and an s.c. ED50 of 75μg/kg. Ro 15-0778 was also evaluated for its ability to prevent testosterone induction of the immature hamster flank organ. The topical ED50 is 0.53 mg/kg and the oral ED50 is 38 mg/kg. This arotinoid is similarly active in mature male hamsters without testosterone treatment. In addition, the retinoid is active topically and orally in reducing the size of the gerbil abdominal sebaceous gland. The compound exhibits no antiandrogenic activity when tested in ventral prostrate and seminal vesicle assays in rats. Additionally, the compound does not have estrogenic activity when tested in the rat uterine weight assay. High doses of Ro 15-0778 in humans did not demonstrate significant sebumsuppressing activity. This study indicates that extra-polation of retinoid data from rodent animal models to activity in human sebaceous glands can not be made with a high degree of certainty. There is a need to develop new, more predictive models for retinoid activity.
Similar content being viewed by others
References
Ebling FJ (1974) Hormonal control and methods of measuring sebaceous gland activity. J Invest Dermatol 62:161–171
Ebling FJ, Randall VA, Skinner J (1981) Local suppression of sebum secretion in rats by topical cyproterone acetate in ethanol. J Invest Dermatol 77:458–463
Ebling FJ, Skinner J (1975) The removal and restitution of hair fat in the rat. Br J Dermatol 92:321–324
Glenn EM, Gray J (1965) Effect of various hormones on the growth and histology of the gerbil (Meriones unguiculatus) abdominal sebaceous gland pad. Endocrinology 76:1115–1123
Goldstein JA, Socha-Szott A, Thomsen RJ, Pochi PE, Shalita AR, Strauss JS (1982) Comparative effect of isotretinoin and etretinate on acne and sebaceous gland secretion. J Am Acad Dermatol 6:760–765
Gomez EC (1981) Differential effect of 13-cis-retinoic acid and an aromatic retinoid (Ro 10-9359) on the sebaceous glands of the hamster flank organ. J Invest Dermatol 75:68–69
Gomez EC (1982) Actions of isotretinoin and etretinate on the pilosebaceous unit. J Am Acad Dermatol 6:746–750
Gomez EC (1985) Hamster flank organ: assessment of drugs modulating sebaceous gland function. In: Maibach HI, Lowe NJ (eds) Models in dermatology, vol 2. Karger, Basel, pp 100–111
Gomez EC, Moskowitz RJ (1980) Effect of 13-cis-retinoic acid on the hamster flank organ. J Invest Dermatol 74:392–397
Kistler A (1985) Structure-activity relationship of retinoids on the differentiation of cultured chick foot skin. In: Saurat JH (ed) Retinoids: new trends in research and therapy. Karger, Basel, pp 309–312
Loeliger P, Bollag W, Mayer H (1980) Arotinoids, a new class of highly active retinoids. Eur J Med Chem Chim Ther 15:9–15
Peck GL, Olsen TG, Butkus D, Pandya M, Arnaud-Battandier J, Gross EG, Windhorst DB, Cheripko J (1982) Isotretinoin versus placebo in the treatment of cystic acne. J Am Acad Dermatol 6:735–745
Pochi PE (1985) Sebaceous gland assay. In: Maibach HI, Lowe NJ (eds) Models in dermatology, vol 2. Karger, Basel, pp 70–75
Pochi PE, Strauss JS (1974) Endocrinologic control of the development and activity of the human sebaceous gland. J Invest Dermatol 62:191–201
Shapiro SS (1986) Retinoids and epithelial differentiation. In: Sherman (ed) Retinoids and cell differentiation. CRC Press, Baton Rouge, Fla., pp 29–51
Shuster S, Thody AJ (1974) The control and measurement of sebum secretion. J Invest Dermatol 62:172–190
Strauss JS, Pochi PE (1969) Recent advances in androgen metabolism and their relationship to the skin. Arch Dermatol Res 100:621–635
Strauss JS, Stranieri AM (1982) Changes in long-term sebum production from isotretinoin therapy. J Am Acad Dermatol 6:751–755
Strauss JS, Kligman AM, Pochi PE (1962) The effects of androgens and estrogens on human sebaceous glands. J Invest Dermatol 39:139–155
Strauss JS, Pochi PE, Downing DT (1976) The sebaceous gland: twenty-five years of progress. J Invest Dermatol 67:90–97
Strauss JS, Davey WP, Denton SJ, Stranieri A (1988) The effect of an orally administered arotinoid, Ro 15-0778, on sebum production in man. Arch Dermatol Res (in press)
Vane FM, Chari SS, Hurley JF, Shapiro SS, Nordstrom KM, Leyden JJ (1987) Concentration of the sebumsuppressing agent, Ro 15-0778, in tissues of test animals and acne patients (Abstr). J Invest Dermatol 88:552
Windhorst DB (1982) The use of isotretinoin in disorders of keratinization. J Am Acad Dermatol 6:708–709
Author information
Authors and Affiliations
Additional information
A. Boris, deceased
Rights and permissions
About this article
Cite this article
Boris, A., Hurley, J., Wong, C.Q. et al. Sebum-suppressing activity of the nonpolar arotinoid Ro 15-0778 in rodents. Arch Dermatol Res 280, 246–251 (1988). https://doi.org/10.1007/BF00513964
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00513964