Circulating bioactive androgens in midlife women.
BACKGROUND
It is important to characterize the biological activity of circulating androgenic steroid hormones during the menopausal transition because these appear to impact the metabolic and cardiovascular health risk factors of women.


OBJECTIVE
The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum.


METHODS
This was a clinically relevant experimental study nested in a sample population of a longitudinal cohort study.


METHODS
The study was conducted at a university laboratory.


METHODS
A receptor-mediated luciferase expression bioassay based on HEK 293 cells that were stably cotransfected with plasmids containing the human androgen receptor and luciferase gene was developed. In 49 samples from menstruating women aged 42-52 yr, total testosterone (T) and SHBG concentrations were measured by immunoassay; free T concentrations were calculated from the total T and SHBG concentrations.


RESULTS
Mean total T concentration of the sample was 1.15 nm (sd 0.46, range 0.57-3.86 nm). The mean bioactive androgen detected was 1.00 nm (sd 0.24, range 0.53-1.60 nm). Calculated free T (mean 0.0156 nm) was significantly lower than the levels of bioactive androgens measured by receptor-mediated bioassay. There was significant positive correlation between bioactive androgen levels and total T values in young women and polycystic ovarian disorder patients, whereas no correlation was found between the two values in middle-aged women.


CONCLUSIONS
An androgen receptor-mediated bioassay can provide additional information in the evaluation of total bioactive androgens in midlife women. Our data suggest that levels of circulating SHBG may have a significant impact on the levels of total circulating bioavailable androgens.
Chen
Jiangang
J
Center for Health and the Environment, University of California, Davis, California 95616, USA.
Sowers
MaryFran R
MR
Moran
Francisco M
FM
McConnell
Daniel S
DS
Gee
Nancy A
NA
Greendale
Gail A
GA
Whitehead
Cheryl
C
Kasim-Karakas
Sidika E
SE
Lasley
Bill L
BL
D000328:Adult; D000367:Age Factors; D000368:Aged; D000728:Androgens / Q000097:blood* / Q000494:pharmacology; D001681:Biological Assay / Q000379:methods*; D015415:Biomarkers; D002478:Cells, Cultured; D002979:Climacteric / Q000097:blood*; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006304:Health Status; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011944:Receptors, Androgen / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D012727:Sex Characteristics; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood; D014158:Transcription, Genetic
D000728:Androgens; D015415:Biomarkers; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D006854:Hydrocortisone