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Testicular Signaling: Team Work in Sperm Production

  • Joana Santiago
  • Daniela Patrício
  • Joana Vieira SilvaEmail author
Chapter
  • 68 Downloads

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 

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

Notes

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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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Joana Santiago
    • 1
  • Daniela Patrício
    • 1
    • 2
  • Joana Vieira Silva
    • 1
    • 3
    • 4
    Email author
  1. 1.Laboratory of Signal Transduction, Department of Medical Sciences, iBiMED—Institute of BiomedicineUniversity of AveiroAveiroPortugal
  2. 2.Department of Chemistry, CICECO, Aveiro Institute of MaterialsUniversity of AveiroAveiroPortugal
  3. 3.i3S - Instituto de Investigação e Inovação em SaúdeUniversity of PortoPortoPortugal
  4. 4.Laboratory of Cell Biology, Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS)University of PortoPortoPortugal

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