Activation of the GPR30 receptor promotes lordosis in female mice

Neuroendocrinology. 2014;100(1):71-80. doi: 10.1159/000365574. Epub 2014 Jul 7.


Background/aims: Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17β-estradiol-bound estrogen receptors (ER), extranuclear signal transduction cascades such as protein kinase A (PKA) are also important in regulating female sexual receptivity. GPR30 (G-protein coupled receptor 30), also known as GPER1, a putative membrane ER (mER), is a G protein-coupled receptor that binds 17β-estradiol with an affinity that is similar to that possessed by the classical nuclear ER and activates both PKA and extracellular-regulated kinase signaling pathways. The high expression of GPR30 in the ventromedial hypothalamus, a region important for lordosis behavior as well as kinase cascades activated by this receptor, led us to hypothesize that GPR30 may regulate lordosis behavior in female rodents.

Method: In this study, we investigated the ability of G-1, a selective agonist of GPR30, to regulate lordosis in the female mouse by administering this agent prior to progesterone in an estradiol-progesterone priming paradigm prior to testing with stud males.

Results: As expected, 17β-estradiol benzoate (EB), but not sesame oil, increased lordosis behavior in female mice. G-1 also increased lordosis behavior in female mice and decreased the number of rejective responses towards male mice, similar to the effect of EB. The selective GPR30 antagonist G-15 blocked these effects.

Conclusion: This study demonstrates that activation of the mER GPR30 stimulates social behavior in a rodent model in a manner similar to EB.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cyclopentanes / pharmacology
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogens / pharmacology
  • Female
  • Mice, Inbred C57BL
  • Posture / physiology*
  • Progesterone / pharmacology
  • Progestins / pharmacology
  • Quinolines / pharmacology
  • Random Allocation
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / metabolism*
  • Reproductive Control Agents / pharmacology
  • Sexual Behavior, Animal / drug effects
  • Sexual Behavior, Animal / physiology*


  • 1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone
  • Cyclopentanes
  • Estrogens
  • GPER1 protein, mouse
  • Progestins
  • Quinolines
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Reproductive Control Agents
  • estradiol 3-benzoate
  • Progesterone
  • Estradiol