TNF-alpha and hyperandrogenism: a clinical, biochemical, and molecular genetic study

J Clin Endocrinol Metab. 2001 Aug;86(8):3761-7. doi: 10.1210/jcem.86.8.7770.

Abstract

To evaluate the role of TNF-alpha in the pathogenesis of hyperandrogenism, we have evaluated the serum TNF-alpha levels, as well as several polymorphisms in the promoter region of the TNF-alpha gene, in a group of 60 hyperandrogenic patients and 27 healthy controls matched for body mass index. Hyperandrogenic patients presented with mildly increased serum TNF-alpha levels as compared with controls (mean[median] +/- SD: 7.2[7.0] +/- 3.3 pg/ml vs. 5.6[4.4] +/- 4.0 pg/ml, P < 0.02). Although no differences in body mass index and insulin resistance indexes were observed between patients and controls, when subjects were classified by body weight, serum TNF-alpha was increased only in lean patients as compared with lean controls, but this difference was not statistically significant when comparing obese patients with obese controls. The TNF-alpha gene polymorphisms studied here (-1196C/T, -1125G/C, -1031T/C, -863C/A, -857C/T, -316G/A, -308G/A, -238G/A, and -163G/A) were equally distributed in hyperandrogenic patients and controls. However, carriers of the -308A variant presented with increased basal and leuprolide-stimulated serum androgens and 17-hydroxyprogesterone levels when considering patients and controls as a group. No differences were observed in serum TNF-alpha levels, body mass index, and insulin resistance indexes, depending on the presence or absence of these variants. In conclusion, our present results suggest that the TNF-alpha system might contribute to the pathogenesis of hyperandrogenism, independent of obesity and insulin resistance. However, elucidation of the precise mechanisms underlying the relationship between the TNF-alpha system and androgen excess is needed before considering TNF-alpha as a significant contributing factor to the development of hyperandrogenism.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-alpha-Hydroxyprogesterone / blood
  • Adrenocorticotropic Hormone
  • Adult
  • Androgens / blood*
  • Blood Glucose / metabolism
  • Body Mass Index
  • DNA / blood
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Genotype
  • Hirsutism / blood
  • Hirsutism / genetics*
  • Hirsutism / physiopathology
  • Humans
  • Hydrocortisone / blood
  • Hyperandrogenism / blood
  • Hyperandrogenism / genetics*
  • Hyperandrogenism / physiopathology*
  • Insulin / blood
  • Leuprolide
  • Luteinizing Hormone / blood
  • Menstrual Cycle
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Reference Values
  • Sex Hormone-Binding Globulin / analysis
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Androgens
  • Blood Glucose
  • Insulin
  • Sex Hormone-Binding Globulin
  • Tumor Necrosis Factor-alpha
  • Estradiol
  • 17-alpha-Hydroxyprogesterone
  • Adrenocorticotropic Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • DNA
  • Leuprolide
  • Hydrocortisone