Phospho-ERK and sex steroids in the mPOA: involvement in male mouse sexual behaviour

J Endocrinol. 2017 Jun;233(3):257-267. doi: 10.1530/JOE-17-0025. Epub 2017 Mar 29.


This paper aimed to investigate the mechanisms triggering ERK phosphorylation and its functional role in male sexual behaviour. ERK1/2-phosphorylated form was detected in the medial preoptic area of the hypothalamus (mPOA) during the sexual stimulation of naive and sexually experienced males who were killed 5 min after the first intromission. This mating-induced ERK phosphorylation was increased in sexually experienced males compared to that in naive mice. The functional role of the ERK1/2 pathway activation during sexual behaviour was explored with the administration of a MEK inhibitor, SL-327 (30 mg/kg, i.p.), 45 min before the contact with a receptive female. Inhibition of ERK phosphorylation was found to decrease sexual motivation in both naive and experienced males without altering their copulatory ability. The mechanisms potentially involved in this rapid ERK1/2 pathway activation were specified ex vivo on hypothalamic slices. A thirty-minute incubation with 100 nM of testosterone (T), dihydrotestosterone (DHT) or oestradiol (E2) led to ERK phosphorylation. No changes were observed after incubation with testosterone 3-(O-carboxymethyl)oxime-BSA (T-BSA), an impermeable to the plasma membrane form of testosterone. All these results indicate that ERK phosphorylation within the mPOA could be a key player in the motivational signalling pathway and considered as an index of sexual motivation. They also demonstrate the involvement of oestrogen receptor (ER) and androgen receptor (AR) transduction pathways in steroid-dependent ERK activation.

Keywords: SL-327; hypothalamic preoptic area; phospho-ERK; sexual behaviour; testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / physiology
  • Phosphorylation
  • Preoptic Area / metabolism*
  • Sexual Behavior, Animal / physiology*
  • Smell / physiology
  • Testosterone / metabolism*


  • Testosterone
  • Extracellular Signal-Regulated MAP Kinases