In vivo effects of a GPR30 antagonist.
Estrogen is central to many physiological processes throughout the human body. We have previously shown that the G protein-coupled receptor GPR30 (also known as GPER), in addition to classical nuclear estrogen receptors (ER and ER), activates cellular signaling pathways in response to estrogen. In order to distinguish between the actions of classical estrogen receptors and GPR30, we have previously characterized G-1 (1), a selective agonist of GPR30. To complement the pharmacological properties of G-1, we sought to identify an antagonist of GPR30 that displays similar selectivity against the classical estrogen receptors. Here we describe the identification and characterization of G15 (2), a G-1 analog that binds to GPR30 with high affinity and acts as an antagonist of estrogen signaling through GPR30. In vivo administration of G15 revealed that GPR30 contributes to both uterine and neurological responses initiated by estrogen. The identification of this antagonist will accelerate the evaluation of the roles of GPR30 in human physiology.
Department of Cell Biology & Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
Megan K
MK
Dennis
Ritwik
R
Burai
Chinnasamy
C
Ramesh
Whitney K
WK
Petrie
Sara N
SN
Alcon
Tapan K
TK
Nayak
Cristian G
CG
Bologa
Andrei
A
Leitao
Eugen
E
Brailoiu
Elena
E
Deliu
Nae J
NJ
Dun
Larry A
LA
Sklar
Helen J
HJ
Hathaway
Jeffrey B
JB
Arterburn
Tudor I
TI
Oprea
Eric R
ER
Prossnitz
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019906:Nuclear Magnetic Resonance, Biomolecular; D011960:Receptors, Estrogen / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction
D004967:Estrogens; C109584:GPER1 protein, human; D008024:Ligands; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled