Evidence for androgen receptor gene expression and growth inhibitory effect of dihydrotestosterone on human adrenocortical cells.
Evidence for the expression of the canonic androgen receptor (AR) in human adrenal cortex has not been provided so far. The aim of the present study was to demonstrate the expression of the AR gene in normal and neoplastic adrenocortical human tissues and in the human adrenocortical cancer cell line, NCI-H295, and then to evaluate the effect of dihydrotestosterone (DHT) on human adrenocortical cell growth. An AR cDNA fragment with the expected size of 262 bp was detected by using reverse transcription (RT)-PCR in normal and neoplastic adrenocortical human tissues and in the neoplastic cell line, demonstrating that the gene for AR is indeed expressed in human adrenal cells. In the human adrenocortical cancer cell line NCI-H295, DHT at physiological concentrations produced a significant reduction in cell proliferation and inhibition of colony formation in soft agar. The inhibitory effect on adrenocortical cell growth was evident after both 24 and 48 h of treatment. The antiandrogens, cyproterone acetate and hydroxyflutamide, were capable of reversing the effects exerted by DHT. The androgen-induced growth inhibitory effect was also detected in primary culture of three non-functioning adrenocortical adenomas. These findings show that the canonic AR is present in human adrenocortical cells and that androgens may have a role in the adrenal cortex by reducing cell proliferation.
Rossi
R
R
Department of Biomedical Sciences and Advanced Therapies - Section of Endocrinology, University of Ferrara, I-44100 Ferrara, Italy.
Zatelli
M C
MC
Valentini
A
A
Cavazzini
P
P
Fallo
F
F
del Senno
L
L
degli Uberti
E C
EC
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000726:Androgen Antagonists / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017373:Cyproterone Acetate / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D017373:Cyproterone Acetate; D005485:Flutamide