Ghrh, or growth hormone-releasing hormone, is a 44-amino-acid peptide primarily expressed in the hypothalamus [2]. It is the primary regulator of pulsatile growth hormone (GH) secretion from the pituitary gland, counteracted by somatostatin [2]. Signaling pathways activated by Ghrh include AC/cAMP/PKA, Ras/Raf/ERK, PI3K/Akt/mTOR and JAK2/STAT3, involved in processes like cell survival, proliferation, and cytokine secretion [1]. Ghrh is also involved in maintaining multisystem homeostasis and has a role in the regulation of the sleep-wake cycle and whole-body energy homeostasis [2,4].

Mutant and transgenic animals with defective Ghrhergic activity display permanently reduced deep non-REM sleep (NREMS), which cannot be reversed by GH supplementation, indicating Ghrh's crucial role in sleep regulation [4]. In the reproductive systems, Ghrh may participate in gonadal function, and reproductive system-related disorders could potentially benefit from hormonal interventions related to the Ghrh axis [5]. In the context of cancer, Ghrh-Rs have become drug targets, and the development of Ghrh-R antagonists has shown anticancer and anti-inflammatory activities [1]. In diabetes and metabolism, Ghrh and its analogs enhance the survival of insulin-producing pancreatic β-cells in vitro and in animal models, suggesting potential for treating metabolic diseases [3].

In conclusion, Ghrh is essential for the regulation of GH secretion, sleep-wake cycle, energy homeostasis, and has implications in multiple disease areas. The study of Ghrh using mutant and transgenic animal models has revealed its role in sleep regulation, reproductive functions, cancer, and diabetes, providing valuable insights for potential therapeutic interventions in these disease conditions.