Abstract
The male gonads, testis, have two main functions: testosterone production (steroidogenesis), a fundamental hormone for the development and maintenance of several physiological functions; and sperm production (spermatogenesis), essential for male fertility. The synthesis of both products is mainly regulated by endocrine hormones, synthesized in the hypothalamus and pituitary gland, and paracrine signals. This chapter will explore the signaling pathways involved in testosterone production by Leydig cells. We will also discuss both classical and non-classical pathways of testosterone action in spermatogenesis, and the contribution of follicle stimulating hormone to spermatogenesis maintenance. Finally, the signaling pathways involved in blood-testis-barrier regulation as well as other paracrine signals involved in spermatogenesis control will be explored. Despite these pathways occur in most somatic cells, they have a unique role in regulating the most peculiar and exceptional process in one of the most complex tissue in male body.
J. Santiago and D. Patrício—Contributed equally.
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- 17OH-Allo:
-
17OH-allopregnanolone
- 17OH-DHP:
-
17OH-dihydroprogesterone
- 17OHPreg:
-
17α-hydroxypregnenolone
- 17OHProg:
-
17α-hydroxyprogesterone
- AA:
-
Arachidonic acid
- AC:
-
Adenylyl cyclase
- AKR1C2/4:
-
Aldo-keto reductase family 1 member C2/4
- AKR1C3:
-
Aldo-keto reductase family 1 member C3
- AKT:
-
RAC-alpha serine/threonine-protein kinase
- AKT1S1:
-
Proline-rich AKT1 substrate 1
- AR:
-
Androgen receptor
- ARE:
-
Androgen response elements
- ATP:
-
Adenosine triphosphate
- BCL6B:
-
B cell CLL/lymphoma 6 member B
- BTB:
-
Blood-Testis-Barrier
- CAM:
-
Calmodulin
- cAMP:
-
Cyclic adenosine monophosphate
- CAR:
-
Coxsackievirus and adenovirus receptor
- CDC42:
-
Cell division control protein 42 homolog
- CDK1:
-
Cyclin D1
- CLDN:
-
Claudin
- CRE:
-
cAMP-response element
- CREB:
-
Cyclic AMP-responsive element-binding protein 1
- CREM:
-
cAMP-responsive element modulators
- CSF1:
-
Colony stimulating factor
- CXCL12:
-
Stromal cell-derived factor 1
- CXCR4:
-
C-X-C chemokine receptor type 4
- CYP11A1:
-
Cholesterol side-chain cleavage enzyme
- CYP17A1:
-
Steroid 17-alpha-hydroxylase/17,20 lyase
- CYP19A1:
-
Aromatase
- DAG:
-
Diacylglycerol
- DHEA:
-
Dehydroepiandrosterone
- DHT:
-
Dihydrotestosterone
- DMRT:
-
Double sex- and mab-3 related transcription factor
- DNA:
-
Deoxyribonucleic acid
- EGF:
-
Epidermal growth factor
- EGFR:
-
Epidermal growth factor receptor
- EGR1:
-
Early growth response protein 1
- ER:
-
Endoplasmic reticulum
- ERBB4:
-
Receptor tyrosine-protein kinase erbB-4
- ERK:
-
Mitogen-activated protein kinase
- ES:
-
Ectoplasmic specialization
- ETV5:
-
ETS translocation variant 5
- FAK:
-
Focal adhesion kinases
- FDX1:
-
Ferredoxin-1
- FDXR:
-
Ferredoxin reductase
- FGF:
-
Fibroblast growth factor
- FSH:
-
Follicle stimulating hormone
- FSHR:
-
Follicle stimulating hormone receptor
- GATA-4:
-
Transcription factor GATA-4
- GDF9:
-
Growth/differentiation factor 9
- GDNF:
-
Glial cell-derived neurotrophic factor
- GFRA1:
-
GDNF family receptor alpha-1
- GNE:
-
Guanine nucleotide exchange factor
- GnRH:
-
Gonadotropin releasing hormone
- GPRC:
-
G protein-coupled receptor
- HSD17B3:
-
17β-hydroxysteroid dehydrogenase type 3
- HSD3B2:
-
3β-hydroxysteroid dehydrogenase type II
- HSP:
-
Heat shock proteins
- ID4:
-
DNA-binding protein 4
- IGF:
-
Insulin-like growth factor
- IL:
-
Interleukins
- IMM:
-
Inner mitochondrial membrane
- INSL3:
-
Insulin-like factor 3
- IP3:
-
Inositol 1,4,5-trisphosphate
- JAM:
-
Junctional adhesion molecules
- KITLG:
-
Stem cell factor/kit ligand
- KO:
-
Knock out
- LC:
-
Leydig Cell
- LDH:
-
Lactate dehydrogenase
- LDHA:
-
L-lactate dehydrogenase A chain
- LH:
-
Luteinizing Hormone
- LHCGR:
-
Luteinizing hormone/choriogonadotropin receptor
- LHX1:
-
LIM homeobox 1
- LICH:
-
Cholesteryl ester hydrolase
- MAPK:
-
Mitogen-activated protein kinase
- MMP9:
-
Matrix metalloproteinase-9
- mTOR:
-
Serine/threonine-protein kinase mTOR
- mTORC1:
-
Mammalian target of rapamycin complex 1
- mTORC2:
-
Mammalian target of rapamycin complex 2
- NF-κB:
-
Nuclear factor-kappa B
- NRG:
-
Neuregulin
- OCLN:
-
Ocludin
- OPRL1:
-
Nociceptin receptor
- PDPK1:
-
Phosphoinositide dependent protein kinase 1
- PDE:
-
Phosphodiesterase
- PGE2:
-
Prostaglandin E2
- PIK3:
-
Phosphatidylinositol 3 kinase
- PIP2:
-
Phosphatidylinositol 4,5-bisphosphate
- PLA2:
-
Phospholipase A2
- PLC:
-
Phospholipase C
- POR:
-
P450 oxidoreductase
- PRKA:
-
Protein kinase A
- PRKB:
-
Protein kinase B
- PRKC:
-
Protein kinase C
- RA:
-
Retinoic acid
- RAF:
-
RAF proto-oncogene serine/threonine-protein kinase
- RAR:
-
Nuclear retinoic receptor
- REC8:
-
Meiotic recombination protein rec8
- RHOX5:
-
Homeobox protein Rhox5
- RNA:
-
Ribonucleic acid
- RPS6K:
-
Ribosomal protein S6 kinase
- RoDH:
-
Retinol dehydrogenase
- RXR:
-
Retinoic X receptor
- SC:
-
Sertoli Cell
- SCAR:
-
Sertoli cells-specific androgen receptor
- SFK:
-
SRC family kinase
- SRC:
-
Proto-oncogene tyrosine-protein kinase Src
- SRD5A2:
-
5α-reductase type II
- SRF:
-
Serum response factor
- SSC:
-
Spermatogonial stem cells
- StAR:
-
Steroidogenic acute regulatory protein
- STF1:
-
Steroidogenic factor 1
- TGF:
-
Transforming growth factor
- TJ:
-
Thigh junctions
- TNF:
-
Tumor necrosis factor
- VEGF:
-
Vascular endothelial growth factor
- VIM:
-
Vimentin
- γ-GTP:
-
γ-glutamyl peptidase
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Acknowledgments
This work was supported by FEDER Funds through Competitiveness and Internationalization Operational Program—COMPETE 2020 and by National Funds through FCT—Foundation for Science and Technology under the project PTDB/BBB-BQB/3804/2014. We are thankful to Institute for Biomedicine—iBiMED (UIDB/04501/2020 and POCI-01-0145-FEDER-007628) for supporting this project. iBiMED is supported by the Portuguese Foundation for Science and Technology (FCT), Compete2020 and FEDER fund. This work was also support by individual grant from FCT of the Portuguese Ministry of Science and Higher Education to JS (SFRH/BD/136896/2018), DP (SFRH/BD/137487/2018) and JVS (SFRH/BPD/123155/2016).
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Santiago, J., Patrício, D., Silva, J.V. (2020). Testicular Signaling: Team Work in Sperm Production. In: Silva, J.V., Freitas, M.J., Fardilha, M. (eds) Tissue-Specific Cell Signaling. Springer, Cham. https://doi.org/10.1007/978-3-030-44436-5_8
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