Effects of androgens and estrogens and catechol and methoxy-estrogen derivatives on mitogen-activated protein kinase (ERK(1,2)) activity in SW-13 human adrenal carcinoma cells.
We tested the effects of 17beta-estradiol as well as its catechol- and methoxy-derivatives, two androgens (DHEA and testosterone), a glucocorticoid (cortisol), a mineralocorticoid (aldosterone), and progesterone on the activity of ERK(1,2), a key component of the ERK/MAPK enzyme phosphorylation cascade, in SW-13 human adrenal carcinoma cells. After a 24-hour exposure SW-13 cells incubated with 10(-5) M concentrations of 17beta-estradiol, its 2-hydroxy or its 2-methoxy derivative, all had elevated ERK activities (196%, 159%, and 275%, respectively) relative to control cells (p < 0.01). Incubation with testosterone resulted in 162% of control ERK activity (p < 0.01), whereas incubation with the far weaker androgen DHEA or with cortisol, aldosterone, or progesterone had no significant effects. These findings suggest sex steroid-specific influences in the induction or activation of signal transduction pathways known to play a crucial role in cellular proliferation and differentiation.
Brown
J W
JW
V.A. Medical Center, and Department of Medicine, University of Miami School of Medicine, FL 33101, USA.
Kesler
C T
CT
Neary
T
T
Fishman
L M
LM
D000310:Adrenal Gland Neoplasms / Q000201:enzymology* / Q000473:pathology; D000728:Androgens / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000728:Androgens; D004967:Estrogens; D020928:Mitogen-Activated Protein Kinases