Chapters and Articles
You might find these chapters and articles relevant to this topic.
Growth Hormone-Releasing Hormone, Somatostatin, and Ghrelin
Additional releasing factors are made in the CTB, including growth hormone-releasing hormone (Berry et al., 1992), somatostatin (Nishihira and Yagihashi, 1978), and ghrelin (Gualillo et al., 2001) and may regulate hGH-V production as well as placental differentiation (Fuglsang et al., 2005).
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B978032340139500005X
Growth Hormone
Growth-hormone-releasing hormone (GHRH) is produced by the arcuate nucleus and induces the release of human growth hormone (hGH) by the anterior pituitary. Insulin-like growth factor-I (IGF-I) is stimulated by GH. IGF-I indirectly inhibits hGH through its stimulation of somatostatin in the hypothalamus. The downregulation of GHRH is accomplished by somatostatin. hGH is critical for linear bone growth during early development, and continues to play a role in tissue maintenance through adulthood. Wakefulness during the time of night when slow-wave sleep is most predominant (first half of the normal sleep period) blunts the release of hGH, most dramatically in men over the mid-twenties. In normal adulthood, 50–75% of hGH is released in the first half of the night, and in men, the association gets stronger with age. In women, the relationship is not as strong.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9780128229637100519
Growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus and acts on the pituitary. The latter secretes growth hormone (GH) which, in turn, stimulates the generation in the liver of insulin-like growth factor I (IGF-I), the anabolic effector hormone of GH. All three hormones have receptors in the brain. GH and IGF-I circulate mostly bound to specific binding proteins; both these hormones cross the blood–brain barrier via the choroid plexus, with their actions on the brain depending on the hormone levels. The actions of GH and IGF-I on the brain and nervous tissue have been demonstrated in animals and humans. Both have a role in neuronal maturation and glial cell maturation. IGF-I has neurotropic and antiapoptotic properties and is required for oligodendrocyte development and myelinization.
The importance of these hormones on the brain has been demonstrated in states of GH/IGF-I deficiency, which results in smaller brains and a variety of organic and functional defects. Hypersecretion of GH/IGF-I, such as in transgenic animals for these hormones, results in larger brains, and a shortened life span due to adverse complications.
There is unequivocal evidence that GH and IGF-I are needed for the normal early development of the brain and psychoneural functions. Whether GH or IGF-I treatment can restore major neural damage and intellectual functions in trauma, aging, or major deficiency states remains controversial.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9780080887838000784
3.1 Growth hormone-releasing hormone
Growth hormone-releasing hormone (GHRH) is an endocrine hormone produced in the hypothalamus and works on its receptor (GHRH-R) in the anterior pituitary to stimulate the release of growth hormone (GH). GH subsequently can engage hepatocytes to produce insulin-like growth factor-1 (IGF-1) and induce lipolysis in adipocytes via promotion of hormone-sensitive lipase. The GHRH analog tesamorelin, which is modified with a hexanoyl moiety at the N-terminus to improve proteolytic stability, has shown benefits in HIV patients with lipodystrophy and GH deficiency to reduce circulating triglycerides and visceral adipose fat [106] and decrease in serum levels of ALT [107]. In HIV patients with NAFLD, tesamorelin (2 mg daily) caused a greater reduction in relative hepatic fat fraction (37%) relative to placebo (therapy group decreased by 32%, whereas a placebo group gained 5%) [108]. As expected, IGF-1 levels increased and visceral adipose tissue decreased, but circulating triglycerides trended to increase after 12 months of treatment. An analysis of biopsied livers demonstrated that tesamorelin increased transcriptional markers of oxidative phosphorylation and decreased gene sets linked to inflammation [109]. Whether these benefits on hepatic fat content translate to non-HIV patients remains to be proven, but recent clinical results with GH in obese NAFL patients [110] lend credence to targeting this biological pathway for NASH benefits. The recently announced phase 3 trial of tesamorelin in general NASH patients will hopefully provide definitive proof. However, the hyperglycemic propensity of GHRH action must be considered when testing in T2D patients or fragile NASH patients as these individuals are predisposed to glycemic derangements. Another consideration for GHRH-based therapy for NASH is that although GH response to GHRH is higher in women than men [111], postmenopausal women have dampened GH secretion following GHRH stimulation [112]. This is important since the prevalence and incidence of NAFLD are higher in men than premenopausal women, yet these trends normalize in postmenopausal women [113]. This suggests that GHRH-based therapies may be more effective if segmented for pre-menopausal women.
Read full article
URL: https://www.sciencedirect.com/science/article/pii/S2212877820302271
Growth Hormone
Growth hormone is secreted by the anterior pituitary gland largely during SWS and mediates the effects of IL-1 on sleep [59]. Growth hormone may be administered exogenously or stimulated endogenously with prolonged wakefulness [60], exercise [61], and growth hormone releasing hormone (ghrelin). Growth hormone releasing hormone stimulates GABAergic neurons in the preoptic area of the hypothalamus [16]. Accordingly, increased growth hormone leads to robust increases in SWS and SWA [62], specifically in men, with either no change in spindle activity [62] or a reduction in spindle activity [63].
Growth hormones play a well-established role in protein synthesis and adult neurogenesis [64,65]. Growth hormone therapy is associated with improved cognitive function in patients with low growth hormone levels and may be an effective treatment for cognitive impairment [64]. SWS may facilitate growth hormone release and thereby influence synaptic plasticity through growth hormone receptors involved in potentiation in the hippocampus and elsewhere in the brain [64,65]. However, SWS increases improve memory [66], independently from whether growth hormone increases or not, suggesting that cognitive benefits from SWS do not depend on growth hormone. It is still possible, however, that growth hormone by itself increases SWA, leading to large-scale neural synchrony and synaptic scaling with the potential to enhance cognitive function.
Read full article
URL: https://www.sciencedirect.com/science/article/pii/S016622361830064X
Growth Hormone
The secretion of growth hormone, essential for tissue growth and protein anabolism, is prompted by ghrelin and growth hormone–releasing hormone (GHRH).10 These hormones are closely associated with the onset and maintenance of SWS and play significant roles in sleep regulation.10,22 This suggests that growth hormone secretion and maintenance of SWS are important for fetal development and the mother's health during pregnancy.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9781416066453001389
d Growth hormone releasing hormone (GRF)
GRF is a 40 to 44 amino acid peptide which has been recently isolated from a human pancreatic tumor and synthesized. In addition, a shorter biologically active fragment of 37 amino acid residues was characterized (Guillemin et al., 1982; Rivier et al., 1982).
GRF was demonstrated in the hypothalamus of primates (Bloch et al., 1983a,b) and the cat (Bugnon et al., 1983). Immunoreactive cell bodies were found in the arcuate and ventromedial nuclei of the hypothalamus with fibers projecting to the median eminence terminating around the portal vessels. In monkey, arcuate and ventromedial GRF cells project to the anterior hypothalamus along the third ventricle and give perineuronal endings in the PVN. Lateral hypothalamic and lateral preoptic areas contain scattered GRF fibers such as found in the premammillary area. Some fibers run around the anterior commissure, fornix and along the optic tract (Bloch et al., 1983a). Maps on the distribution of GRF in rat brain are not yet available.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9780444903778500053
Growth hormone-releasing hormone
Growth hormone-releasing hormone (GHRH) is produced mainly in the Ncl. arcuatus and the ventromedial hypothalamus. It is produced by posttranslational splitting of N- and C-terminal parts of a 108 amino acid-long prohormone. In humans, two subtypes can be distinguished. While percentage-wise the far larger fraction has 44 amino acids (GHRH(1–44)NH2), a smaller fraction lacks the last four amino acids (GHRH(1–40)OH). However, since the first 29 amino acids are responsible for the biological activity, the two GHRH subtypes are in effect equipotent. The breakdown of the highly stable metabolites GHRH(3–44) NH2 is caused by inactivating peptidases.
Whereas GH, IGF-1, and some neurotransmitters (e.g., GABA) inhibit secretion, other neurotransmitters (e.g., acetylcholine, dopamine, noradrenalin, and serotonin), hormones (e.g., ghrelin), alpha2-receptor agonists (e.g., clonidine), and alpha2-receptor antagonists (e.g., propranolol) promote secretion by GHRH-producing neurons. Their axons extend to the median eminence, from which GHRH reaches the pituitary gland. After binding to its specific G protein-coupled receptor (GHRHR), GHRH causes an elevation in intracellular cAMP concentrations, activation of the enzyme adenylate cyclase, and an influx of free calcium in target cells. In the anterior pituitary, these mechanisms cause the transcription, synthesis, and secretion of GH.
GHRH has also been identified in numerous extrahypothalamic tissues (e.g., ovary, pancreas, placenta, and uterus), but its functions there have yet to be fully clarified. GHRH is known to have a sleep regulating effect, while a modulating effect on eating behavior is also discussed. Very rarely, ectopic GHRH production is observed, for example, in patients with pancreatic tumors or carcinoids. An accompanying acromegaly can result.
Intravenous application of GHRH is followed in minutes by a dose-dependent increase in serum GH levels. Peak levels are reached after 15–45 min, with a return to starting values after 90–120 min. Both repeated administration of high volumes and continuous infusion of GHRH downregulate GHRHR, which leads to a decline in GH production. Unlike GnRHR, however, GHRHR retains a residual sensitivity.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B978012819949700007X
Growth Hormone–Releasing Hormone, Somatostatin, and Ghrelin
Regulators of the GH axis, including GH-releasing hormone,96 somatostatin (also known as GH-inhibiting hormone),97 and gherlin,98 the endogenous GH secretagogue, have all been localized to human cytotrophoblasts. They are all potential regulators of hGH-V production or paracrine regulators of placental differentiation99 but their roles in pregnancy have not been defined.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9780323352147000135
Growth hormone-releasing hormone and somatostatin
The growth hormone-releasing hormone neurons in ARC release the neuropeptide GHRH, which triggers secretion of the growth hormone (GH) from the pituitary gland (Mayo et al., 2000). GH, in turn, induces the hepatic expression of insulin-like growth factor 1 that controls bone epiphyses, muscle and adipose tissue development, growth plates development, and glucose homeostasis. In the human ARC-ME, GHRH neurons and the majority of somatostatin-immunoreactive neurons receive a dense innervation from substance P (SP) fibers indicating that substance P influences growth via action on GHRH and somatostatin neurons (Luu et al., 2020), which provide input to GHRH neurons. Such innervation may at least partially mediate the somatostatin effect on growth, in addition to the somatostatin effects on GH cells in PD. GHRH neurons are also approached by enkephalinergic axonal varicosities (Proudan et al., 2015), which may mediate the well-known modulatory effects on growth. Moreover, catecholaminergic, NPY-, and CRH-immunoreactive axon varicosities abut on the surface of the GHRH neurons and may represent the morphological substrate of the impact of stress (Peroski et al., 2016). Studies in humans have shown an increase in the number of GHRH neurons during prolonged illness prior to death (Goldstone et al., 2003).
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B978012820107700015X