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Modulation of Cyclic AMP Levels in Fallopian Tube Cells by Natural and Environmental Estrogens
- Source :
- Cells, Vol 10, Iss 1250, p 1250 (2021), Cells, Volume 10, Issue 5
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Autocrine/paracrine factors generated in response to 17β-estradiol (E2) within the fallopian tube (FT) facilitate fertilization and early embryo development for implantation. Since cyclic AMP (cAMP) plays a key role in reproduction, regulation of its synthesis by E2 may be of biological/pathophysiological relevance. Herein, we investigated whether cAMP production in FT cells (FTCs) is regulated by E2 and environmental estrogens (EE’s<br />xenoestrogens and phytoestrogens). Under basal conditions, low levels of extracellular cAMP were detectable in bovine FTCs (epithelial cells and fibroblasts<br />1:1 ratio). Treatment of FTCs with forskolin (AC<br />adenylyl cyclase activator), isoproterenol (β-adrenoceptor agonist) and IBMX (phosphodiesterase (PDE) inhibitor) dramatically (&gt<br />10 fold) increased cAMP<br />whereas LRE1 (sAC<br />soluble AC inhibitor) and 2’,5’-dideoxyadenosine (DDA<br />transmembrane AC (tmAC)) inhibitor decreased cAMP. Comparable changes in basal and stimulated intracellular cAMP were also observed. Ro-20-1724 (PDE-IV inhibitor), but not milrinone (PDE-III inhibitor) nor mmIBMX (PDE-I inhibitor), augmented forskolin-stimulated cAMP levels, suggesting that PDE-IV dominates in FTCs. E2 increased cAMP levels and CREB phosphorylation in FTCs, and these effects were mimicked by EE’s (genistein, 4-hydroxy-2’,4’,6’-trichlorobiphenyl, 4-hydroxy-2’,4’,6’-dichlorobiphenyl). Moreover, the effects of E2 and EE were blocked by the tmAC inhibitor DDA, but not by the ERα/β antagonist ICI182780. Moreover, BAPTA-AM (intracellular-Ca2+ chelator) abrogated the effects of E2, but not genistein, on cAMP suggesting differential involvement of Ca2+. Treatment with non-permeable E2-BSA induced cAMP levels and CREB-phosphorylation<br />moreover, the stimulatory effects of E2 and EEs on cAMP were blocked by G15, a G protein-coupled estrogen receptor (GPER) antagonist. E2 and IBMX induced cAMP formation was inhibited by LRE1 and DDA suggesting involvement of both tmAC and sAC. Our results provide the first evidence that in FTCs, E2 and EE’s stimulate cAMP synthesis via GPER. Exposure of the FT to EE’s and PDE inhibitors may result in abnormal non-cyclic induction of cAMP levels which may induce deleterious effects on reproduction.
- Subjects :
- 0301 basic medicine
IBMX
Phosphodiesterase Inhibitors
Genistein
2700 General Medicine
Receptors, G-Protein-Coupled
Adenylyl cyclase
chemistry.chemical_compound
0302 clinical medicine
Cyclic AMP
Phosphorylation
Biology (General)
Cyclic AMP Response Element-Binding Protein
Cells, Cultured
fallopian tube
Forskolin
Estradiol
Chemistry
Phosphodiesterase
General Medicine
10175 Clinic for Reproductive Endocrinology
Polychlorinated Biphenyls
endocrine disruptors
Receptors, Estrogen
Female
infertility
GPER
Adenylyl Cyclases
Agonist
medicine.medical_specialty
medicine.drug_class
QH301-705.5
610 Medicine & health
030209 endocrinology & metabolism
Article
03 medical and health sciences
Internal medicine
medicine
Animals
Autocrine signalling
Fallopian Tubes
hormones
Phosphoric Diester Hydrolases
Epithelial Cells
Estrogens
Fibroblasts
030104 developmental biology
Endocrinology
fertilization
Cattle
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 10
- Issue :
- 1250
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....bee2af9078608fda3d9d417335e2c0e2