Estrogen-regulated synthesis of neurotensin in neurosecretory cells of the hypothalamic arcuate nucleus in the female rat.

Neurotensin (NT) is implicated as a neurohormone in mammals, yet the peptide's neuroendocrine role remains to be determined. NT immunoreactivity has been observed in neurosecretory cells of the arcuate nucleus and paraventricular nucleus, and data suggest that NT release into hypophysial portal blood mediates a component of PRL secretion that is female specific and dependent on ovarian steroids. In the present study, in situ hybridization histochemistry and immunohistochemistry were used to investigate the regulation of NT gene expression in hypothalamic neurosecretory regions of adult rats. In ovariectomized females, estradiol induced expression of messenger RNA (mRNA) encoding NT and neuromedin N (NT/N mRNA) in the dorsomedial division of the arcuate nucleus. In contrast, estradiol did not appreciably alter NT/N mRNA expression in the ventrolateral division of the arcuate nucleus, where labeled cells were numerous, or in the paraventricular nucleus, where labeled cells were virtually absent. Estradiol also increased NT immunoreactivity in the external zone of the median eminence, confirming the neuroendocrine phenotype of NT cells in the dorsomedial division, as well as estrogen-regulated synthesis of NT in this system. In the dorsomedial division of cycling females, NT/N mRNA-expressing cells were significantly more numerous at proestrus than at diestrus, consistent with differences in plasma estradiol levels at these stages. In this same region, NT/N mRNA-expressing cells were significantly more numerous in proestrous females than in gonad-intact males. These results imply that estrogen-regulated release of NT at the median eminence subserves one or more sexually differentiated functions and are consistent with the involvement of tuberoinfundibular NT in estrogen-dependent secretion of PRL or GnRH on the afternoon of proestrus.