Sex Steroid Receptors Cheat Sheet

This is a cheat sheet I made to understand the role of estrogen and progestin receptors in sexual behavior. If you are studying basic neuroendocrinology, this might be a useful resource.






Results in rodents



Estrogen receptor (ER)

Knock-out (KO) ERa gene Completely eliminates hormonal induction of feminine sexual behavior
ERb KO ERb gene §  No apparent effect in ovariectomized (OVX) hormone-injected mice

§  Extends the period of behavioral estrus

§  Enhances receptivity in estrous-cycling mice


double knockout

§  Infertile

§  Decreased levels of sexual receptivity




Results in rodents


Progestin receptor (PR)

PRAKO mice §  Showed minimal progesterone (P) -facilitated lordosis in the presence of males

§  dominant PR-B isoform alone was incapable of mediating the effects of P on sexual behavior


§  Essential role in progesterone-facilitated sexual behavior

PR-B PRKBKO §  Improved PR-A-dependent receptivity with experience

§  Lesser role



  Experiment Result
Dopamine (DA) agonists DA agonist + P antagonists DA facilitates sexual behavior by indirectly activating PRs

(acts on both isoform)


(PKA activator)



Protein kinase A =cAMP-dependent protein kinase

Primarily mediated via PR-A isoform


  • Each isoform of PR may be involved in signaling routes leading to facilitation of sexual behavior, but PR-A seems to have the dominant role in most situations, and PR-B involvement seems to depend upon the mode of activation of the receptor.
  • ER down regulates alpha-ER in most neuroanatomical areas
  • Downregulation of PRs leads to estrous termination and the refractory period
  • Progesterone downregulates its own receptors
  • Functional participation of both the isoforms is critical for P-mediated effects on sexual receptivity
  • Thus, both isoforms of PR, probably via heterodimerization, appear to be required in the RU38486 effects on ligand-independent PR-mediated lordosis.


Ligand-Independent Activation of PRs

  • DA agonists can also activate PRs== blocked by P antagonists
  • Facilitation by dopaminergic agonists was blocked by progesterone antagonists, antisense oligonucleotides directed at the PR mRNA or in PRKO mice
  • SKF 81297= DA agonist


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