17beta-estradiol inhibits soluble guanylate cyclase activity through a protein tyrosine phosphatase in PC12 cells.
Besides its involvement in reproductive functions, estrogen protects against the development of cardiovascular diseases. The guanylate cyclase/cGMP system is known to exert potent effects on the regulation of blood pressure and electrolyte balance. We examined whether 17beta-estradiol can affect soluble guanylate cyclase in PC12 cells. The results indicate that 17beta-estradiol decreases cGMP levels in PC12 cells. 17beta-Estradiol decreases sodium nitroprusside (SNP)-stimulated, but not atrial natriuretic factor-stimulated cGMP formation in PC12 cells, indicating that 17beta-estradiol decreases cGMP levels by inhibiting the activity of soluble guanylate cyclase. 17beta-Estradiol also stimulates protein tyrosine phosphatase activities in PC12 cells and dephosphorylates at least three proteins. Addition of sodium vanadate, a protein tyrosine phosphatase inhibitor, blocks the inhibitory effects of 17beta-estradiol on soluble guanylate cyclase activity in PC12 cells. Furthermore, transfection of SHP-1, a protein tyrosine phosphatase, into PC12 cells inhibits both basal and SNP-stimulated guanylate cyclase activity. Amino acid analysis also reveals that the 70-kDa subunit of soluble guanylate cyclase contains the SHP-1 substrate consensus sequence. These results suggest that 17beta-estradiol inhibits soluble guanylate cyclase activity through SHP-1.
Chen
Z J
ZJ
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Che
D
D
Vetter
M
M
Liu
S
S
Chang
C H
CH
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D009599:Nitroprusside / Q000494:pharmacology; D016716:PC12 Cells; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012995:Solubility; D014162:Transfection; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009599:Nitroprusside; D014638:Vanadates; D004958:Estradiol; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat; D006162:Guanylate Cyclase