Endogenous hydrogen sulfide (H2S) produced by cystathionine beta-synthase (CBS) and cystathionine-gamma lyase (CSE) has emerged as a novel uterine vasodilator contributing to pregnancy-associated increases in uterine blood flow, which safeguard pregnancy health. Uterine artery (UA) H2S production is stimulated via exogenous estrogen replacement and is associated with elevated endogenous estrogens during pregnancy through the selective upregulation of CBS without altering CSE. However, how endogenous estrogens regulate uterine artery CBS expression in pregnancy is unknown. This study was conducted to test a hypothesis that endogenous estrogens selectively stimulate UA CBS expression via specific estrogen receptors (ER). Treatment with E-2 beta (0.01 to 100 nM) stimulated CBS but not CSE mRNA in organ cultures of fresh UA rings from both NP and P (gestational day 20, GD20) rats, with greater responses to all doses of E-2 beta tested in P vs. NP UA. ER antagonist ICI 182,780 (ICI, 1 mu M) completely attenuated E-2 beta-stimulated CBS mRNA in both NP and P rat UA. Subcutaneous injection with ICI 182,780 (0.3 mg/rat) of GD19 P rats for 24 h significantly inhibited UA CBS but not mRNA expression, consistent with reduced endothelial and smooth muscle cell CBS (but not CSE) protein. ICI did not alter mesenteric and renal artery CBS and CSE mRNA. In addition, ICI decreased endothelial nitric oxide synthase mRNA in UA but not in mesenteric or renal arteries. Thus, pregnancy-augmented UA CBS/H2S production is mediated by the actions of endogenous estrogens via specific ER in pregnant rats.
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Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, Brazil
Yasuhara, Fabiana
Oliveira Gomes, Gisele Renata
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Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, Brazil
Oliveira Gomes, Gisele Renata
Siu, Erica Rosanna
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Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, Brazil
Siu, Erica Rosanna
Suenaga, Claudia Igushi
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Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, Brazil
Suenaga, Claudia Igushi
Marostica, Elisabeth
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Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, Brazil
Marostica, Elisabeth
Porto, Catarina Segreti
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Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, Brazil
Porto, Catarina Segreti
Magalhaes Lazari, Maria Fatima
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Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 Sao Paulo, Brazil