Neurotensin gene expression increases during proestrus in the rostral medial preoptic nucleus: Potential for direct communication with gonadotropin-releasing hormone neurons

Neurotensin (NT)-containing neurons in the rostral portion of the medial pr eoptic nucleus (rMPN) of the brain may play a key role in regulating the pa ttern of secretion of GnRH, thereby influencing the reproductive cycle in f emales. The major goals of this study were to determine whether NT messenge r RNA (mRNA) levels in the rMPN exhibit a unique pattern of expression in t emporal association with the preovulatory LH surge and to assess whether NT neurons may communicate directly with GnRH neurons. We analyzed NT gene ex pression in rats using in situ hybridization over the day of proestrus and compared this with diestrous day 1. We also determined whether the high-aff inity NT receptor (NT1) is expressed in GnRH neurons using dual-label in si tu hybridization and whether this expression varies over the estrous cycle. We found that NT mRNA levels in the rMPN increase significantly on the day of proestrus, rising before the LH surge. No such change was detected on d iestrous day 1, when the LH surge does not occur. Furthermore, we observed that a significant number of GnRH neurons coexpress NT1 mRNA and that the n umber of GnRH neurons expressing NT1 mRNA peaks on proestrus. Together with previous findings, our results suggest that increased expression of NT in the rMPN may directly stimulate GnRH neurons on proestrus, contributing to the LH surge. In addition, our results suggest that responsiveness of GnRH neurons to NT stimulation is enhanced on proestrus due to increased express ion of NT receptors within GnRH neurons.