Soluble Guanylyl Cyclase alpha1 Subunit As a Novel Biomarker to Evaluate Endocrine Disruptors Exposition

Presentation Number: SAT 252
Date of Presentation: April 1st, 2017

Sonia A. Ronchetti*1, Agustina Gurruchaga1, Georgina Cordeiro1, Analía Gabriela Ricci2, Beatriz Haydee Duvilanski3 and Jimena P. Cabilla1
1INBIOMED (UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina, 2IByME-CONICET, Buenos Aires, 3INBIOMED (UBA-CONICET), Buenos Aires, Argentina

Abstract

Endocrine disruptors (EDs) are compounds that interfere in the action of endogenous hormones. A particular class of EDs called xenoestrogens, mimic cell responses normally induced by estrogen (E2).

The main nitric oxide receptor soluble guanylyl cyclase (sGC) is a cytosolic heterodimer composed by two subunits, alpha and beta, and catalyzes cGMP formation. It is ubiquitously present throughout all the zoological scale. E2 differentially affects sGC subunits by increasing alpha1 (a1) and decreasing beta1 (b1) expression. Previously we have shown that a1 expression is particularly sensitive to E2 levels in vivo and in vitro.

The aim of the present work was to investigate the expression of a1 as an indicator of EDs exposition in some estrogen-responsive cell lines.

Lactosomatotroph-derived pituitary cell line GH3 and endometrial tumor cell line ECC-1 were incubated with several EDs with or without xenoestrogenic activity for 48 h. a1 and b1 expression was determined by western blot. 1 nM cadmium (Cd) and 1 nM arsenic (As) treatments increased a1 expression in GH3 cells (a1 relative units (RU) as % of control; Cd: 152±10*; As: 145.6±13*, E2: 236.5±21.2***, *p<0.05, ***p<0.001), while b1 levels were unaffected. Similar results were observed in ECC-1 cells. These effects showed to be specific for E2 or E2-like compounds since it was not reproduced after incubation with other proliferation inducers (a1 RU as % of control; 10 μM forskolin: 135±23; 100 μM 3-isobutyl-1-methylxanthine (IBMX): 104.3±14.2) or prolactin, a classic downstream E2-induced gene (a1 RU as % of control; 1 ng/mL PRL: 120±25). Moreover, ethynylestradiol (EE2) and diethylstilbestrol (DES), were shown to increase a1 expression (a1 RU as % of control; 1 nM EE2=160±14%**, 1 nM DES=172±13%**, p<0.01) without affecting b1 levels. Other organochlorines as hexachlorobenzene (HCB) and chlorpyrifos (CPF) also increased a1 levels (a1 RU as % of control; 5 nM HCB=174±14**, 50 nM CPF 128±10*, *p<0.05, **p<0.01).

Altogether, these results support soluble guanylyl cyclase alpha1 subunit as a novel potential biomarker to rapidly assess estrogen receptor-dependent and independent EDs exposure in vitro.

 

Nothing to Disclose: SAR, AG, GC, AGR, BHD, JPC