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Testicular Signaling: Team Work in Sperm Production

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.

Keywords

  • Steroidogenesis
  • Endocrine signaling
  • Spermatogenesis
  • Blood-testis-barrier

J. Santiago and D. Patrício—Contributed equally.

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Fig. 8.1
Fig. 8.2
Fig. 8.3
Fig. 8.4
Fig. 8.5

Abbreviations

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., Freitas, M., Fardilha, M. (eds) Tissue-Specific Cell Signaling. Springer, Cham. https://doi.org/10.1007/978-3-030-44436-5_8

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