The hypothalamic–pituitary–adrenal (HPA) axis has long served as a classical model of brain–body communication, illustrating how neuroendocrine signaling maintains physiological homeostasis. While endocrine hormones have traditionally been thought to act on peripheral organs, emerging evidence reveals that several such hormones, including insulin, corticoids, ghrelin, and thyroid hormones, also influence central nervous system (CNS) function. These actions are supported by the presence of corresponding hormone receptors within specific brain regions. However, the mechanisms by which these peripheral signals access the brain remain insufficiently explored, particularly regarding the role of brain barriers, including the blood–brain barrier (BBB) and blood–cerebrospinal fluid barrier (BCSFB). These barriers not only regulate molecular transport into the brain but may also serve as active participants in neuroendocrine communication. This review synthesizes current findings on representative peripheral hormones originating from the pancreas, small intestine, and thyroid gland. We focus on their interactions with brain barriers, identify known transport mechanisms, and discuss how these processes are altered in metabolic and neurological disorders. Understanding the crosstalk between peripheral hormones and brain barriers may provide novel insights into the regulation of CNS function and the pathophysiology of hormone-related brain disorders.
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