Entry
Name
Growth hormone synthesis, secretion and action - Homo sapiens (human)
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
hsa04935 Growth hormone synthesis, secretion and action
Ortholog table
Network
Element
N00907 GH-Jak-STAT signaling pathway
N00910 GHRHR-PKA-GH signaling pathway
Drug
D02250 Octreotide acetate (JAN)
D04666 Lanreotide acetate (JAN/USAN)
D06495 Octreotide acetate (USP)
D09015 Tesamorelin acetate (USAN)
D10497 Pasireotide diaspartate
D10566 Pasireotide pamoate (JAN)
D11033 Lutetium (177Lu) oxodotreotide (INN)
D11486 Lonapegsomatropin (USAN/INN)
D11651 Edotreotide gallium Ga-68
D12431 Lutetium Lu177 edotreotide (USAN)
D12478 Paltusotine hydrochloride (USAN)
D12907 Actinium Ac 225 dotatate (USAN)
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
2691 GHRH; growth hormone releasing hormone [KO:K05260 ]
2692 GHRHR; growth hormone releasing hormone receptor [KO:K04584 ]
2770 GNAI1; G protein subunit alpha i1 [KO:K04630 ]
2773 GNAI3; G protein subunit alpha i3 [KO:K04630 ]
2771 GNAI2; G protein subunit alpha i2 [KO:K04630 ]
1385 CREB1; cAMP responsive element binding protein 1 [KO:K05870 ]
1386 ATF2; activating transcription factor 2 [KO:K04450 ]
468 ATF4; activating transcription factor 4 [KO:K04374 ]
10488 CREB3; cAMP responsive element binding protein 3 [KO:K09048 ]
90993 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
64764 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
84699 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
148327 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
9586 CREB5; cAMP responsive element binding protein 5 [KO:K09047 ]
1388 ATF6B; activating transcription factor 6 beta [KO:K09049 ]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
1442 CSH1; chorionic somatomammotropin hormone 1 [KO:K05438 ]
1443 CSH2; chorionic somatomammotropin hormone 2 [KO:K05438 ]
1444 CSHL1; chorionic somatomammotropin hormone like 1 [KO:K05438 ]
51738 GHRL; ghrelin and obestatin prepropeptide [KO:K05254 ]
2693 GHSR; growth hormone secretagogue receptor [KO:K04284 ]
112609 MRAP2; melanocortin 2 receptor accessory protein 2 [KO:K25968 ]
2767 GNA11; G protein subunit alpha 11 [KO:K04635 ]
3708 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
3709 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
3710 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
779 CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857 ]
775 CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850 ]
776 CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851 ]
778 CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
6772 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
6774 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
6776 STAT5A; signal transducer and activator of transcription 5A [KO:K11223 ]
6777 STAT5B; signal transducer and activator of transcription 5B [KO:K11224 ]
3667 IRS1; insulin receptor substrate 1 [KO:K16172 ]
8660 IRS2; insulin receptor substrate 2 [KO:K07187 ]
8471 IRS4; insulin receptor substrate 4 [KO:K17446 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
3479 IGF1; insulin like growth factor 1 [KO:K05459 ]
3726 JUNB; JunB proto-oncogene, AP-1 transcription factor subunit [KO:K09028 ]
8651 SOCS1; suppressor of cytokine signaling 1 [KO:K04694 ]
8835 SOCS2; suppressor of cytokine signaling 2 [KO:K04695 ]
9021 SOCS3; suppressor of cytokine signaling 3 [KO:K04696 ]
3483 IGFALS; insulin like growth factor binding protein acid labile subunit [KO:K17256 ]
3486 IGFBP3; insulin like growth factor binding protein 3 [KO:K10138 ]
9564 BCAR1; BCAR1 scaffold protein, Cas family member [KO:K05726 ]
1398 CRK; CRK proto-oncogene, adaptor protein [KO:K04438 ]
1399 CRKL; CRK like proto-oncogene, adaptor protein [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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