Abstract
Body homeostasis is predominantly controlled by hormones secreted by endocrine organs. The central nervous system contains several important endocrine structures, including the hypothalamic-pituitary axis. Conventionally, neurohormones released by the hypothalamus and the pituitary gland (hypophysis) have received much attention owing to the unique functions of the end hormones released by their target peripheral organs (e.g., glucocorticoids released by the adrenal glands). Recent advances in mouse genetics have revealed several important metabolic functions of hypothalamic neurohormone-expressing cells, many of which are not readily explained by the action of the corresponding classical downstream hormones. Notably, the newly identified functions are better explained by the action of conventional neurotransmitters (e.g., glutamate and GABA) that constitute a neuronal circuit. In this review, we discuss the regulation of appetite and metabolism by hypothalamic neurohormone-expressing cells, with a focus on the distinct contributions of neurohormones and neurotransmitters released by these neurons.
Highlights
The hypothalamus is a vital region of the brain that regulates whole-body homeostasis
A recent study demonstrated that lentiviral knockdown of corticotropinreleasing hormone (CRH) in the central amygdala (CeA) resulted in elevation of the basal but not the stress-induced CORT level[72], which suggests that CeA CRH neurons downregulate the basal activity of the HPA axis
These cutting-edge techniques have revealed several previously unknown mechanisms underlying homeostatic regulation by hypothalamic neurohormone-expressing cells at the molecular, cellular, and circuit levels. These techniques have been applied primarily to understand the contribution of nonneuroendocrine or neural mechanisms to feeding behavior and metabolism
Summary
All neurons that express neurohormones are not “neuroendocrine” cells; some neurohormone-expressing neurons (e.g., CRH and TRH neurons) do not project to the median eminence[11,12]. Neurohormone-expressing cells comprise neuroendocrine and non-neuroendocrine cells, and the term “neuroendocrine cells” may only be used to refer to neurons that project to the median eminence and release neurohormones. A subset of CRH neurons located in the paraventricular nucleus of the hypothalamus (PVH) labeled with peripherally injected fluorogold showed retrograde labeling of fluorescent beads injected into the lateral hypothalamic area (LHA)[13]. These results suggest that neuroendocrine and nonneuroendocrine cells are not always completely segregated within a single population of neurohormoneexpressing cells. The non-neuroendocrine neurohormone-expressing cells of the hypothalamus constitute a neural circuitry that utilizes conventional neurotransmitters. We discuss recent studies that investigated the role of conventional neurotransmitters released by these neurons
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