Distribution of ghrelin-immunoreactive neuronal networks in the human hypothalamus.

Ghrelin has been discovered as the endogenous ligand of the growth hormone secretagogue receptor (GHS-R). It stimulates growth hormone secretion and also potently increases food intake. To date, ghrelin is the only known peripheral orexigenic hormone. Recent studies have demonstrated that in addition to peripheral organs, ghrelin is also synthesized in the hypothalamus. In the present study, we examined the distribution of the ghrelin-immunoreactive (IR) elements in the human hypothalamus. Ghrelin-IR fibers were widely distributed throughout the hypothalamus. Based on the thickness of fibers, major subtypes of ghrelin-IR axons were observed: thick fibers with large varicosities and very fine axons with or without small varicosities. Dense networks of ghrelin-IR axons were observed in the hypothalamic suprachiasmatic, paraventricular, supraoptic, dorsomedial, ventromedial and infundibular nuclei and in the periventricular area. Ghrelin-IR axons also appeared in the external layer of the pituitary stalk. Ghrelin-IR cell bodies were not detected. Since hypothalamic regions innervated by ghrelin-IR axons also take part in the regulation of food intake and energy balance, the centrally synthesized ghrelin may play a major role in the central regulation of energy metabolism in humans.

Interconnection between orexigenic neuropeptide Y- and anorexigenic alpha-melanocyte stimulating hormone-synthesizing neuronal systems of the human hypothalamus.

Peripheral feeding-related hormones such as leptin, insulin, and ghrelin exert their main central effects through neuropeptide Y- (NPY) synthesizing and alpha-melanocyte-stimulating hormone- (alpha-MSH) synthesizing neurons of the hypothalamic arcuate nucleus. In rodents, recent reports have described an asymmetric signaling between these neuron populations by showing that while NPY influences alpha-MSH-synthesizing neurons, the melanocortin-receptor agonist Melanotan II (MTII) does not modulate the electrophysiological properties of NPY neurons. The functional neuroanatomy of the relationship between these cell populations is unknown in humans. The aim of the current study was to analyze the putative relationship of the orexigenic NPY and anorexigenic alpha-MSH systems in the infundibular nucleus of the human hypothalamus, the analogue of the rodent arcuate nucleus. Double-labeling fluorescent immunocytochemistry for NPY and alpha-MSH was performed on postmortem sections of the human hypothalamus. The sections were analyzed by confocal laser microscopy. Both NPY- and alpha-MSH-immunoreactive (IR) neurons were embedded in dense, intermingling networks of NPY- and alpha-MSH-IR axons in the human infundibular nucleus. NPY-IR varicosities were observed in juxtaposition to all alpha-MSH-IR neurons. The mean number of NPY-IR axon varicosities on the surface of an alpha-MSH-IR neuron was approximately six. The majority of NPY-IR neurons were also contacted by alpha-MSH-IR varicosities, although, the number of such contacts was lower (two alpha-MSH-IR varicosities per NPY neuron). In summary, the present data demonstrate that these two antagonistic, feeding-related neuronal systems are interconnected in the infundibular nucleus, and the neuronal wiring possesses an asymmetric character in the human hypothalamus.