Blood-borne hormones acting in the mediobasal hypothalamus, like those controlling food intake, require relatively direct access to target chemosensory neurons of the arcuate nucleus (ARC). An anatomical substrate for this is a permeable microvasculature with fenestrated endothelial cells in the ARC, a system that has awaited comprehensive documentation. Here, the immunofluorescent detection of endothelial fenestral diaphragms in the rat ARC allowed us to quantitate permeable microvessels throughout its rostrocaudal extent. We have determined that permeable microvessels are part of the subependymal plexus irrigating exclusively the ventromedial (vm) ARC from the subadjacent neuroendocrine median eminence. Unexpectedly, permeable microvessels were concentrated proximal to the pituitary stalk. This marked topography strongly supports the functional importance of retrograde blood flow from the pituitary to the vmARC, therefore making a functional relationship between peripheral long-loop, pituitary short-loop, and neuroendocrine ultra-short loop feedback, altogether converging for integration in the vmARC (formerly known as the hypophysiotrophic area), thereby so pivotal as a multicompetent brain endocrinostat.

No abstract

A cDNA encoding a GABA(A) receptor subunit was isolated from rat brain. The predicted protein is 70% identical to the human epsilon-subunit. It was recently reported [Sinkkonen et al. (2000), J. Neurosci., 20, 3588-3595] that the rodent epsilon-subunit mRNA encoded an additional sequence ( approximately 400 residues). We provide evidence that human and rat epsilon-subunit are similar in size. The distribution of cells expressing the GABA(A) epsilon-subunit was examined in the rat brain. In situ hybridization histochemistry revealed that epsilon-subunit mRNA is expressed by neurons located in septal and preoptic areas, as well as in various hypothalamic nuclei, including paraventricular, arcuate, dorsomedial and medial tuberal nuclei. The mRNA was also detected in major neuronal groups with broad-range influence, such as the cholinergic (basal nucleus), dopaminergic (substantia nigra compacta), serotonergic (raphe nuclei), and noradrenergic (locus coeruleus) systems. Immunohistochemistry using an affinity-purified antiserum directed towards the N-terminal sequence unique to the rat epsilon-subunit revealed the presence of epsilon-subunit immunoreactivity over the somatodendritic domain of neurons with a distribution closely matching that of mRNA-expressing cells. Moreover, using in situ hybridization, alpha3, theta and epsilon GABA(A) subunit mRNAs were all detected with an overlapping distribution in neurons of the dorsal raphe and the locus coeruleus. Our results suggest that novel GABA(A) receptors may regulate, neuroendocrine and modulatory systems in the brain.

No abstract

Adrenocorticotropic hormone (ACTH) release from anterior pituitary corticotropes is greatly increased during peripheral inflammation induced by lipopolysaccharide (LPS) administration. Interleukin-6 (IL-6) is thought to participate in LPS-induced ACTH release, but whether or not corticotropes are directly targeted by this cytokine is unclear. Therefore, we investigated the expression and activation of IL-6 signaling components in the pituitary of rats 2 and 4 h after administration of LPS (250 µg/kg). Intraperitoneal LPS treatment provoked the nuclear translocation of signal transducer and activator of transcription 3 (STAT-3) and Fos expression in the anterior pituitary lobe, as demonstrated by immunohistochemistry. By using in situ hybridization, we demonstrated that suppressor of cytokine signaling 3 (SOCS-3) and c-fos mRNAs were significantly induced by the LPS treatment in the anterior lobe of the pituitary. Dual in situ hybridization revealed that most corticotropes expressed IL-6 receptor and gp130 mRNAs, and that 2 h after LPS treatment, SOCS-3 and c-fos mRNAs were induced in corticotropes. Our results suggest that LPS-induced IL-6 could regulate the hypothalamo-pituitary-adrenal axis by directly targeting corticotropes during peripheral inflammation.