TNF-alpha and hyperandrogenism: a clinical, biochemical, and molecular genetic study.
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.
Escobar-Morreale
H F
HF
Department of Endocrinology, Hospital Ramón y Cajal, 28034 Madrid, Spain. hector.escobar@uam.es
Calvo
R M
RM
Sancho
J
J
San Millán
J L
JL
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000728:Androgens / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D004247:DNA / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D006628:Hirsutism / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D017588:Hyperandrogenism / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D016729:Leuprolide; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D000728:Androgens; D001786:Blood Glucose; D007328:Insulin; D012738:Sex Hormone-Binding Globulin; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA; D016729:Leuprolide; D006854:Hydrocortisone