Testicular Signaling: Team Work in Sperm Production



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.


Steroidogenesis Endocrine signaling Spermatogenesis Blood-testis-barrier 











Arachidonic acid


Adenylyl cyclase


Aldo-keto reductase family 1 member C2/4


Aldo-keto reductase family 1 member C3


RAC-alpha serine/threonine-protein kinase


Proline-rich AKT1 substrate 1


Androgen receptor


Androgen response elements


Adenosine triphosphate


B cell CLL/lymphoma 6 member B






Cyclic adenosine monophosphate


Coxsackievirus and adenovirus receptor


Cell division control protein 42 homolog


Cyclin D1




cAMP-response element


Cyclic AMP-responsive element-binding protein 1


cAMP-responsive element modulators


Colony stimulating factor


Stromal cell-derived factor 1


C-X-C chemokine receptor type 4


Cholesterol side-chain cleavage enzyme


Steroid 17-alpha-hydroxylase/17,20 lyase










Double sex- and mab-3 related transcription factor


Deoxyribonucleic acid


Epidermal growth factor


Epidermal growth factor receptor


Early growth response protein 1


Endoplasmic reticulum


Receptor tyrosine-protein kinase erbB-4


Mitogen-activated protein kinase


Ectoplasmic specialization


ETS translocation variant 5


Focal adhesion kinases




Ferredoxin reductase


Fibroblast growth factor


Follicle stimulating hormone


Follicle stimulating hormone receptor


Transcription factor GATA-4


Growth/differentiation factor 9


Glial cell-derived neurotrophic factor


GDNF family receptor alpha-1


Guanine nucleotide exchange factor


Gonadotropin releasing hormone


G protein-coupled receptor


17β-hydroxysteroid dehydrogenase type 3


3β-hydroxysteroid dehydrogenase type II


Heat shock proteins


DNA-binding protein 4


Insulin-like growth factor




Inner mitochondrial membrane


Insulin-like factor 3


Inositol 1,4,5-trisphosphate


Junctional adhesion molecules


Stem cell factor/kit ligand


Knock out


Leydig Cell


Lactate dehydrogenase


L-lactate dehydrogenase A chain


Luteinizing Hormone


Luteinizing hormone/choriogonadotropin receptor


LIM homeobox 1


Cholesteryl ester hydrolase


Mitogen-activated protein kinase


Matrix metalloproteinase-9


Serine/threonine-protein kinase mTOR


Mammalian target of rapamycin complex 1


Mammalian target of rapamycin complex 2


Nuclear factor-kappa B






Nociceptin receptor


Phosphoinositide dependent protein kinase 1




Prostaglandin E2


Phosphatidylinositol 3 kinase


Phosphatidylinositol 4,5-bisphosphate


Phospholipase A2


Phospholipase C


P450 oxidoreductase


Protein kinase A


Protein kinase B


Protein kinase C


Retinoic acid


RAF proto-oncogene serine/threonine-protein kinase


Nuclear retinoic receptor


Meiotic recombination protein rec8


Homeobox protein Rhox5


Ribonucleic acid


Ribosomal protein S6 kinase


Retinol dehydrogenase


Retinoic X receptor


Sertoli Cell


Sertoli cells-specific androgen receptor


SRC family kinase


Proto-oncogene tyrosine-protein kinase Src


5α-reductase type II


Serum response factor


Spermatogonial stem cells


Steroidogenic acute regulatory protein


Steroidogenic factor 1


Transforming growth factor


Thigh junctions


Tumor necrosis factor


Vascular endothelial growth factor




γ-glutamyl peptidase



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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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  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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