Entry
Name
Growth hormone synthesis, secretion and action - Mus musculus (house mouse)
Description
Growth hormone (GH) is a peptide hormone secreted from the anterior pituitary and plays a critical role in cell growth, development, and metabolism throughout the body. GH secretion occurs episodically and is primarily under the control of two hypothalamic neuroendocrine hormones: GH-releasing hormone (GHRH), which stimulates GH secretion, and somatostatin, which inhibits GH secretion. GHRH interacts with a G protein-coupled receptor (GHRHR) in somatotroph cells to activate the cAMP signaling pathway, which leads to increased GH mRNA transcription and release. Once released into the circulation, GH binds to cell-surface GHR in target tissues such as liver, muscle, bone, and adipose tissue. Binding leads to activation of JAK2 that in turn triggers an array of signaling cascade including Raf-MEK-ERK, PI3K-Akt, and STAT5. ERK, Akt, and STAT5 all promote growth via the synthesis and secretion of IGF-1.
Class
Organismal Systems; Endocrine system
BRITE hierarchy
Pathway map
mmu04935 Growth hormone synthesis, secretion and action
Ortholog table
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
14601 Ghrh; growth hormone releasing hormone [KO:K05260 ]
14602 Ghrhr; growth hormone releasing hormone receptor [KO:K04584 ]
12912 Creb1; cAMP responsive element binding protein 1 [KO:K05870 ]
11909 Atf2; activating transcription factor 2 [KO:K04450 ]
11911 Atf4; activating transcription factor 4 [KO:K04374 ]
12913 Creb3; cAMP responsive element binding protein 3 [KO:K09048 ]
26427 Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048 ]
208647 Creb3l2; cAMP responsive element binding protein 3-like 2 [KO:K09048 ]
208677 Creb3l3; cAMP responsive element binding protein 3-like 3 [KO:K09048 ]
78284 Creb3l4; cAMP responsive element binding protein 3-like 4 [KO:K09048 ]
231991 Creb5; cAMP responsive element binding protein 5 [KO:K09047 ]
12915 Atf6b; activating transcription factor 6 beta [KO:K09049 ]
18736 Pou1f1; POU domain, class 1, transcription factor 1 [KO:K09363 ]
208188 Ghsr; growth hormone secretagogue receptor [KO:K04284 ]
244958 Mrap2; melanocortin 2 receptor accessory protein 2 [KO:K25968 ]
14682 Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634 ]
14672 Gna11; guanine nucleotide binding protein, alpha 11 [KO:K04635 ]
16438 Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958 ]
16439 Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959 ]
16440 Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960 ]
12292 Cacna1s; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857 ]
12288 Cacna1c; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850 ]
12289 Cacna1d; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851 ]
54652 Cacna1f; calcium channel, voltage-dependent, alpha 1F subunit [KO:K04853 ]
20416 Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279 ]
216148 Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447 ]
20418 Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448 ]
271849 Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449 ]
14784 Grb2; growth factor receptor bound protein 2 [KO:K04364 ]
20662 Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
20663 Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
15461 Hras; Harvey rat sarcoma virus oncogene [KO:K02833 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
20846 Stat1; signal transducer and activator of transcription 1 [KO:K11220 ]
20848 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
20850 Stat5a; signal transducer and activator of transcription 5A [KO:K11223 ]
20851 Stat5b; signal transducer and activator of transcription 5B [KO:K11224 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
12703 Socs1; suppressor of cytokine signaling 1 [KO:K04694 ]
216233 Socs2; suppressor of cytokine signaling 2 [KO:K04695 ]
12702 Socs3; suppressor of cytokine signaling 3 [KO:K04696 ]
16005 Igfals; insulin-like growth factor binding protein, acid labile subunit [KO:K17256 ]
16009 Igfbp3; insulin-like growth factor binding protein 3 [KO:K10138 ]
12927 Bcar1; breast cancer anti-estrogen resistance 1 [KO:K05726 ]
12928 Crk; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438 ]
12929 Crkl; v-crk avian sarcoma virus CT10 oncogene homolog-like [KO:K04438 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference
Authors
Nishad R, Mukhi D, Menon R K, Pasupulati A.
Title
Growth Hormone and Metabolic Homeostasis
Journal
Eur Med J 6:78-87 (2018)
Reference
Authors
Lu M, Flanagan JU, Langley RJ, Hay MP, Perry JK
Title
Targeting growth hormone function: strategies and therapeutic applications.
Journal
Reference
Authors
Argetsinger LS, Carter-Su C
Title
Mechanism of signaling by growth hormone receptor.
Journal
Reference
Authors
Carter-Su C, Schwartz J, Smit LS
Title
Molecular mechanism of growth hormone action.
Journal
Reference
Authors
Carter-Su C, Rui L, Herrington J
Title
Role of the tyrosine kinase JAK2 in signal transduction by growth hormone.
Journal
Reference
Authors
Dehkhoda F, Lee CMM, Medina J, Brooks AJ
Title
The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects.
Journal
Reference
Authors
Carter-Su C, Schwartz J, Argetsinger LS
Title
Growth hormone signaling pathways.
Journal
Reference
Authors
Berryman DE, Henry B, Hjortebjerg R, List EO, Kopchick JJ
Title
Developments in our understanding of the effects of growth hormone on white adipose tissue from mice: implications to the clinic.
Journal
Reference
Authors
Zhu T, Goh EL, LeRoith D, Lobie PE
Title
Growth hormone stimulates the formation of a multiprotein signaling complex involving p130(Cas) and CrkII. Resultant activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK).
Journal
Reference
Authors
Choi S (ed).
Title
Encyclopedia of Signaling Molecules
Journal
Reference
Authors
Gracia-Navarro F, Castano JP, Malagon MM, Sanchez-Hormigo A, Luque RM, Hickey GJ, Peinado JR, Delgado E, Martinez-Fuentes AJ
Title
Research progress in the stimulatory inputs regulating growth hormone (GH) secretion.
Journal
Reference
Authors
Bertherat J
Title
Nuclear effects of the cAMP pathway activation in somatotrophs.
Journal
Reference
Authors
Tuggle CK, Trenkle A
Title
Control of growth hormone synthesis.
Journal
Reference
Authors
Cohen LE, Hashimoto Y, Zanger K, Wondisford F, Radovick S
Title
CREB-independent regulation by CBP is a novel mechanism of human growth hormone gene expression.
Journal
Reference
Authors
Khatib N, Gaidhane S, Gaidhane AM, Khatib M, Simkhada P, Gode D, Zahiruddin QS
Title
Ghrelin: ghrelin as a regulatory Peptide in growth hormone secretion.
Journal
Reference
Authors
Lengyel AM
Title
From growth hormone-releasing peptides to ghrelin: discovery of new modulators of GH secretion.
Journal
Reference
Authors
Anderson LL, Jeftinija S, Scanes CG, Stromer MH, Lee JS, Jeftinija K, Glavaski-Joksimovic A
Title
Physiology of ghrelin and related peptides.
Journal
Reference
Authors
Camina JP, Carreira MC, Micic D, Pombo M, Kelestimur F, Dieguez C, Casanueva FF
Title
Regulation of ghrelin secretion and action.
Journal
Reference
Authors
Yang SK, Steyn F, Chen C
Title
Influence of membrane ion channel in pituitary somatotrophs by hypothalamic regulators.
Journal
Reference
Authors
Melmed S
Title
Acromegaly pathogenesis and treatment.
Journal
Reference
Authors
Rouault AAJ, Rosselli-Murai LK, Hernandez CC, Gimenez LE, Tall GG, Sebag JA
Title
The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a.
Journal
Related pathway
KO pathway
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