Expression of sex-determining genes in human sebaceous glands and their possible role in the pathogenesis of acne

J Eur Acad Dermatol Venereol. 2006 Aug;20(7):846-52. doi: 10.1111/j.1468-3083.2006.01663.x.

Abstract

Background: The human skin, especially the sebaceous gland, is a steroidogenic organ similar to the gonads and adrenal cortex, possessing all the enzymes required for steroid sex-hormone synthesis and metabolism. Factors regulating cutaneous steroidogenesis associated with disease status remain largely unknown.

Objective: We hypothesized that transcription factors involved in sex formation and regulation of steroidogenesis in the classical steroidogenic organs are also expressed in the sebaceous glands. Their possible role in the pathogenesis of acne were investigated.

Methods: We used reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and Western blotting to analyse the expression of SF-1, WT-1, SRY, SOX-9 and DAX-1 mRNAs and their proteins in cultured human sebocytes and the facial skin of acne patients.

Results: The in situ hybridization study showed SOX-9 mRNA mainly localized in basal keratinocytes, the basal layer of the sebaceous glands and eccrine glands. Immortalized human sebaceous gland cells (SZ95) expressed mRNA for SOX-9, WT-1 and DAX-1 but not for SF-1 or SRY. The expression of DAX-1 protein was slightly inhibited by 10(-6) m oestradiol (E2) at 6 h but enhanced by 10(-6) m dihydrotestosterone (DHT) at 48 h. The facial expression of SOX-9 seemed to be higher in the acne-prone male patients, while DAX-1 was stronger in subjects without acne, although both were statistically insignificant.

Conclusion: Our findings confirm the expression of some sex-determining genes in human sebaceous glands. Further studies on a larger patient population including the normal controls are needed to elucidate the functional significance of these transcription factors in the pathogenesis of acne.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris / genetics*
  • Acne Vulgaris / metabolism
  • Adolescent
  • Adult
  • Cells, Cultured
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression*
  • Genes, Wilms Tumor
  • Genes, sry / genetics
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • SOX9 Transcription Factor
  • Sebaceous Glands / cytology
  • Sebaceous Glands / metabolism*
  • Sex Determination Processes
  • Sex Differentiation / genetics*
  • Skin / metabolism*
  • Steroidogenic Factor 1
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • NR0B1 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Steroidogenic Factor 1
  • Transcription Factors