Dihydrotestosterone and estradiol-17beta mutually neutralize their inhibitory effects on human vascular smooth muscle cell growth in vitro.
We reported previously that high concentrations of either estradiol-17beta (E(2)) or dihydrotestosterone (DHT) inhibit growth of human cultured vascular smooth muscle cells (VSMC), mediated by cell membrane receptors and MAP-kinase-kinase activity (MEK). We now tested whether the presence of the opposite gender's dominant sex hormone modifies these effects. We incubated VSMC with various concentrations of E(2) and DHT or protein bound hormones (E(2)-BSA or T-BSA), alone or in various combinations. High concentration of E(2) or E(2)-BSA inhibited VSMC growth and stimulated MEK. In the presence of 3 nM DHT, high concentration of E(2) no longer inhibited (3)[H] thymidine incorporation or increased MEK. Moreover, when high DHT concentration (300 nM) was added to VSMC exposed to high E(2), VSMC growth actually increased without change in MEK. DHT at 300 nM suppressed VSMC growth and increased MEK while 0.3 nM E(2) had only marginal effect on this interaction, and 30 nM E(2) reversed the inhibitory effect of DHT on cell growth. The inhibitory effects of both E(2) and DHT on VSMC cell growth and the stimulation of MEK was apparently mediated by cell membrane receptors, as it persisted when bovine serum albumin (BSA)-bound hormones were used. Further, inhibition of VSMC growth induced by E(2)-BSA was reversed in the presence of T-BSA and vice versa. These results suggest that while female and male sex hormones affect VSMC growth similarly, they interfere in a dose-, hormone- and MEK-dependent manner with each other's effect.
Somjen
Dalia
D
Institute of Endocrinlology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, 6 Weizman Street, Tel-Aviv, Israel. dalias@tasmc.health.gov.il
Kohen
Fortune
F
Gayer
Batya
B
Knoll
Esther
E
Many
Ariel
A
Stern
Naftali
N
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D013196:Dihydrotestosterone; D012710:Serum Albumin, Bovine; D004958:Estradiol; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases