Exclusive androgenic effect of dehydroepiandrosterone in sebaceous glands of rat skin.

In order to analyze the hormonal effects of dehydroepiandrosterone (DHEA) in skin sebaceous glands, the precursor steroid was administered to ovariectomized (OVX) female Sprague-Dawley rats at a dose of 30 mg applied on the dorsal skin, twice daily, for 3, 6 and 12 months. In a parallel experiment, female OVX rats were treated with DHEA at the same daily percutaneous dose of 30 mg, alone or in combination with the antiandrogen Flutamide or the pure antiestrogen EM-800, for 12 months, in order to determine the androgenic and/or estrogenic components of DHEA action. Treatment of female OVX rats with DHEA resulted in a similar mild to moderate hyperplasia of the sebaceous glands of both dorsal (site of application) and ventral skin, as illustrated by an increase in the number and size of the acini. The above-indicated effects were observed at all time intervals studied, beginning at 3 months of treatment, and they were not further increased after longer term administration of DHEA (for 6 and 12 months). The addition of Flutamide to DHEA treatment completely prevented the DHEA-induced changes in the sebaceous glands, whereas the antiestrogen EM-800 had no effect. The present data indicate an exclusive androgenic stimulatory action of DHEA on the sebaceous glands, thus pointing out the importance of local intracrine DHEA transformation into androgens for skin anatomical integrity and function, while showing that estrogens, if active in rat skin, do not originate from DHEA.

[1]  A. Howell,et al.  Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp. , 1998, The Journal of endocrinology.

[2]  ScienceDirect Baillière's clinical endocrinology and metabolism , 1998 .

[3]  C. Labrie,et al.  Long‐term inhibitory effects of a novel anti‐estrogen on the growth of ZR‐75‐1 and MCF‐7 human breast cancer tumors in nude mice , 1997, International journal of cancer.

[4]  C. Labrie,et al.  Comparative effects of 28‐day treatment with the new anti‐estrogen EM‐800 and tamoxifen on estrogen‐sensitive parameters in intact mice , 1997, International journal of cancer.

[5]  C. Labrie,et al.  Combined Effects of Dehydroepiandrosterone and EM-800 on Bone Mass, Serum Lipids, and the Development of Dimethylbenz(A)Anthracene-Induced Mammary Carcinoma in the Rat. , 1997, Endocrinology.

[6]  J. Simard,et al.  Characterization of the effects of the novel non‐steroidal antiestrogen EM‐800 on basal and estrogen‐induced proliferation of T‐47D, ZR‐75‐1 and MCF‐7 human breast cancer cells in vitro , 1997, International journal of cancer.

[7]  J. Simard,et al.  (S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active nonsteroidal antiestrogen. , 1997, Journal of medicinal chemistry.

[8]  C. Labrie,et al.  Combined effects of dehydroepiandrosterone and EM-800 on bone mass, serum lipids, and the development of dimethylbenz(A)anthracene-induced mammary carcinoma in the rat. , 1997, Endocrinology.

[9]  J. Simard,et al.  Localization and regulation of expression of the FAR-17A gene in the hamster flank organs. , 1996, The Journal of investigative dermatology.

[10]  F. Labrie,et al.  Adrenal steroid precursors exert potent androgenic action in the hamster sebaceous glands of flank organs and ears. , 1996, Endocrinology.

[11]  J. Simard,et al.  The 3β-Hydroxysteroid Dehydrogenase/Isomerase Gene Family: Lessons from Type II 3β-HSD Congenital Deficiency , 1996 .

[12]  F. Labrie,et al.  Additive in vivo growth-inhibitory effects of flutamide and finasteride on androgen-sensitive Shionogi 115 carcinoma , 1996 .

[13]  K. Taskén,et al.  Signal Transduction in Testicular Cells , 1996, Ernst Schering Research Foundation Workshop.

[14]  J. Simard,et al.  DHEA and Peripheral Androgen and Estrogen Formation: Intracrinology , 1995, Annals of the New York Academy of Sciences.

[15]  D. Gagné,et al.  Widespread tissue distribution of steroid sulfatase, 3β-hydroxysteroid dehydrogenase/Δ5-Δ4isomerase(3β-HSD), 17β-HSD5α-reductase and aromatase activities in the rhesus monkey , 1994, Molecular and Cellular Endocrinology.

[16]  J. Simard,et al.  11 Structure, regulation and role of 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase and aromatase enzymes in the formation of sex steroids in classical and peripheral intracrine tissues , 1994 .

[17]  Y. Labrie,et al.  Characterization, Expression, and Immunohistochemical Localization of 5α-Reductase in Human Skin , 1994 .

[18]  H. Sasano,et al.  Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. , 1993, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[19]  M. Dumont,et al.  Characterization, Expression, and Immunohistochemical Localization of 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase in Human Skin , 1992 .

[20]  T. H. van der Kwast,et al.  Localization of androgen receptors in human skin by immunohistochemistry: implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands. , 1992, The Journal of endocrinology.

[21]  A. Messenger,et al.  Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp. , 1992, The Journal of endocrinology.

[22]  M. Takahashi,et al.  Distribution of 17β-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues , 1992, The Journal of Steroid Biochemistry and Molecular Biology.

[23]  M. Dumont,et al.  Structure and tissue-specific expression of 3ß-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase genes in human and rat classical and peripheral steroidogenic tissues , 1992, The Journal of Steroid Biochemistry and Molecular Biology.

[24]  F. Labrie Intracrinology , 1991, Molecular and Cellular Endocrinology.

[25]  Y. Lachance,et al.  Full Length cDNA Structure and Deduced Amino Acid Sequence of Human β-Hydroxy-5-Ene Steroid Dehydrogenase , 1989 .

[26]  C. Labrie,et al.  Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate. , 1988, Endocrinology.

[27]  J. Simard,et al.  Characteristics of interaction of the antiandrogen flutamide with the androgen receptor in various target tissues , 1986, Molecular and Cellular Endocrinology.

[28]  R. Santen,et al.  Tissue production of androgens in women with acne. , 1985, Journal of the American Academy of Dermatology.

[29]  R. Lobo,et al.  5α-Reductase Activity in the Genital Skin of Hirsute Women* , 1985 .

[30]  R. Lobo,et al.  Increased 5α-reductase activity in idiopathic hirsutism*† , 1985 .

[31]  E. Steinberger,et al.  Acne and hyperandrogenism. , 1984, Journal of the American Academy of Dermatology.

[32]  D. Sgoutas,et al.  Elevated free testosterone levels in women with acne. , 1983, Archives of dermatology.

[33]  W. Cunliffe,et al.  The Relationship Between the In Vitro Activity of 3β-Hydroxysteroid Dehydrogenase Δ4–5-Isomerase in Human Sebaceous Glands and Their Secretory Activity In Vivo , 1983 .

[34]  M. Sawaya,et al.  Transformation of dehydroepiandrosterone into dihydrotestosterone by isolated cells from rat preputial gland. , 1983, Journal of steroid biochemistry.

[35]  B. Rich,et al.  Plasma androgens in women with acne vulgaris. , 1983, The Journal of investigative dermatology.

[36]  I. Mowszowicz,et al.  Androgen binding capacity and 5 alpha-reductase activity in pubic skin fibroblasts from hirsute patients. , 1983, The Journal of clinical endocrinology and metabolism.

[37]  S. Marynick,et al.  Androgen excess in cystic acne. , 1983, The New England journal of medicine.

[38]  C. Migeon,et al.  Androgen receptors. , 1983, Clinics in endocrinology and metabolism.

[39]  G. Chrousos,et al.  Adrenal function in women with idiopathic acne. , 1982, The Journal of investigative dermatology.

[40]  I. Mowszowicz,et al.  Androgen receptor in human skin cytosol. , 1981, The Journal of clinical endocrinology and metabolism.

[41]  T. Spelsberg,et al.  Isolation and characterization of the estrogen receptor in human skin. , 1980, The Journal of clinical endocrinology and metabolism.

[42]  I. Mowszowicz,et al.  Male Pseudohermaphroditism: A Comparative Study of One Patient with 5α-Reductase Deficiency and Three Patients with the Complete Form of Testicular Feminization* , 1979 .

[43]  Susumu Takavasu METABOLISM AND ACTION OF ANDROGEN IN THE SKIN , 1979 .

[44]  S. Takayasu Metabolism and action of androgen in the skin. , 1979, International journal of dermatology.

[45]  M. Hodgins,et al.  Distribution of androgen metabolizing enzymes in isolated tissues of human forehead and axillary skin. , 1978, The Journal of endocrinology.

[46]  M. Forest,et al.  Pattern of plasma dehydroepiandrosterone sulfate levels in humans from birth to adulthood: evidence for testicular production. , 1978, The Journal of clinical endocrinology and metabolism.

[47]  J. Strauss,et al.  Skin surface lipid composition, acne, pubertal development, and urinary excretion of testosterone and 17-ketosteroids in children. , 1977, The Journal of investigative dermatology.

[48]  I. Mowszowicz,et al.  Androgen production and skin metabolism in hirsutism. , 1977, Journal of Endocrinology.

[49]  F. Sharp,et al.  Metabolism of androgens in vitro by human foetal skin. , 1976, The Journal of endocrinology.

[50]  S. Shuster,et al.  Effects of 5alpha-reduced androgens on preputial-gland size and lipogenic activity. , 1976, Biochemical Society transactions.

[51]  S. Shuster,et al.  Sebaceous lipogenesis and androgen metabolism in acne. , 1976, Biochemical Society transactions.

[52]  M. Hodgins,et al.  Steroid metabolism in human skin: its relation to sebaceous-gland growth and acne vulgaris. , 1976, Biochemical Society transactions.

[53]  B. Lutsky,et al.  Metabolism and effects of androgens in hamster flank organs. , 1974, Endocrinology.

[54]  G. Plewig Acne vulgaris: proliferative cells in sebaceous glands , 1974, The British journal of dermatology.

[55]  J. Thomas,et al.  Androgen metabolism in the skin of hirsute women. , 1974, The Journal of clinical endocrinology and metabolism.

[56]  M. Hodgins,et al.  Metabolism of androgens in vitro by human facial and axillary skin. , 1973, The Journal of endocrinology.

[57]  D. Shaw,et al.  The metabolism of testosterone by human male scalp skin. , 1973, The Journal of endocrinology.

[58]  M. Hodgins,et al.  The metabolism of androgens in rat preputial glands. , 1973, Steroids.

[59]  W. Drucker,et al.  Biologic Activity of Dehydroepiandrosterone Sulfate in Man1 , 1972 .

[60]  S. Shuster,et al.  Skin virilism in women with hrsutism. , 1972, The Journal of endocrinology.

[61]  W. Drucker,et al.  Biologic activity of dehydroepiandrosterone sulfate in man. , 1972, The Journal of clinical endocrinology and metabolism.

[62]  G. Sansone,et al.  Differential rates of conversion of testosterone to dihydrotestosterone in acne and in normal human skin--a possible pathogenic factor in acne. , 1971, The Journal of investigative dermatology.

[63]  E. Bottoms,et al.  Osteoporosis, Skin Collagen, and Androgen , 1970, British medical journal.

[64]  J. Strauss,et al.  Chemical composition of human skin surface lipids from birth to puberty. , 1970, The Journal of investigative dermatology.

[65]  I. Toth,et al.  Transformation in vitro of [4-14-C]-dehydroepiandrosterone into 7-oxygenated derivatives by normal human male and female skin tissue. , 1969, The Journal of investigative dermatology.

[66]  J. Milne THE METABOLISM OF ANBHOGENS BY SEBACEOUS GLANDS * , 1969 .

[67]  J. Strauss,et al.  Sebaceous gland response in man to the administration of testosterone, delta-4-androstenedione, and dehydroisoandrosterone. , 1969, The Journal of investigative dermatology.

[68]  G. Oertel,et al.  Metabolism and excretion of C19-and C18-steroids by human skin. , 1969, European journal of biochemistry.

[69]  J. Milne The metabolism of androgens by sebaceous glands. , 1969, The British journal of dermatology.

[70]  R. Neri,et al.  Biological studies on an anti-androgen (SH 714). , 1967, European journal of pharmacology.

[71]  D. Berliner,et al.  Transformation and conjugation of dehydroepiandrosterone by human skin. , 1967, The Journal of clinical endocrinology and metabolism.

[72]  J. Milne,et al.  THE DISTRIBUTION OF HYDROXYSTEROID DEHYDROGENASE IN HUMAN SEBACEOUS GLANDS. , 1966, The British journal of dermatology.

[73]  F. Serri,et al.  CHAPTER I – THE DEVELOPMENT OF SEBACEOUS GLANDS IN MAN , 1963 .

[74]  J. Strauss,et al.  CHAPTER XIV – THE HORMONAL CONTROL OF HUMAN SEBACEOUS GLANDS* , 1963 .

[75]  R. Ellis CHAPTER 20 – Ageing of the Human Male Scalp1 , 1958 .

[76]  S. Rothman,et al.  Hormonal effects on sebaceous glands in the white rat. II. The effect of the pituitary-adrenal axis. , 1954, The Journal of investigative dermatology.

[77]  H. Hurley,et al.  The physiology of the human axillary apocrine sweat gland. , 1953, The Journal of investigative dermatology.

[78]  S. Rothman,et al.  Some effects of ACTH, cortisone, progesterone and testosterone on sebaceous glands in the white rat. , 1953, The Journal of investigative dermatology.

[79]  J. Hamilton,et al.  The sebaceous glands of the hamster; morphological effects of androgens on integumentary structures. , 1950, The American journal of anatomy.

[80]  William Montagna,et al.  Growth potentials and mitotic division in the sebaceous glands of the rabbit , 1949, The Anatomical record.

[81]  Ebling Fj The effect of sex hormones on the sebaceous glands of the female albino rat. , 1948 .

[82]  C. A. Pfeiffer,et al.  EFFECTS OF SEX HORMONES UPON BODY GROWTH, SKIN, HAIR AND SEBACEOUS GLANDS IN THE RAT , 1943 .

[83]  S. R. Reynolds,et al.  PERIPHERAL VASCULAR ACTION OF ESTROGEN, OBSERVED IN THE EAR OF THE RABBIT , 1940 .

[84]  The Inhibitory Effect , 2022 .

[85]  S. Shuster,et al.  Effects of % Reduced Androgens on Preputial-Gland Size and Lipogenic Activity , 2022 .