Distribution of corticotropin releasing hormone receptor immunoreactivity in the rat hypothalamus: coexpression in neuropeptide Y and dopamine neurons in the arcuate nucleus.

摘要

An abundance of physiological data suggests an interaction between neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) in the regulation of endocrine and autonomic functions. Previously, studies in our laboratory have indicated that NPY neurons in the arcuate nucleus of the hypothalamus (ARH) project to and come in close contact with CRH neurons in the paraventricular nucleus of the hypothalamus (PVH). Conversely, it has been demonstrated that the ventromedial portion of the ARH, an area containing NPY neurons, displays CRH receptor binding and CRH receptor mRNA. These data suggest a possible reciprocal feedback regulation between NPY and CRH neurons. The ARH also contains several other populations of neurons that may be targets of the CRH system and express CRH receptors; most notable are tuberoinfundibular dopaminergic neurons (TIDA). The PVH is an important component in the regulation of prolactin secretion and may play a role in the suppression of TIDA activity, which is a critical step in the prolactin stress response. The purpose of the present study was to characterize the distribution and cellular localization of CRH R(1) receptor-like immunoreactivity (CRH R(1)-ir) in the rat hypothalamus and to determine the phenotype of neurons in the ARH that contain CRH R(1)-ir. CRH R(1)-ir was present throughout the rat brain. Hypothalamic regions with the highest levels of immunostaining were the supraoptic nucleus, magnocellular PVH, ARH, and suprachiasmatic nucleus. Double label immunofluorescence was used to demonstrate that CRH R(1)-ir in the ARH was localized to NPY cell bodies. Furthermore, TIDA neurons in the ARH also displayed CRH R(1)-ir. However, despite an abundance of CRH R(1)-ir cells in the ARH, CRH-ir fiber innervation to the ARH was extremely sparse. Therefore, although this study provides neuroanatomical evidence for direct CRH R(1) regulation of ARH NPY and TIDA neurons in the rat, it is not consistent with the idea of a reciprocal feedback loop and suggests the involvement of other CRH-like ligands, such as urocortin.