The expression of neurotrophins and their receptors in the prenatal and adult human testis: evidence for functions in Leydig cells.
Previous studies have demonstrated local functions for neurotrophins in the developing and mature testis of rodents. To examine whether these signaling molecules are present and also potentially active in the human testis, we characterized immunohistochemically the expression and cellular localization of the known neurotrophins and their receptors during prenatal testicular development as well as in the adult human testis. Results obtained revealed the presence of nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3 and 4, as well as neurotrophin receptors p75(NTR), TrkA, TrkB, and TrkC during testis morphogenesis. These proteins were also detectable in the adult human testis, and their local expression could be confirmed largely by immunoblot and RT-PCR analyses. Remarkably, the Leydig cells were found to represent the predominant neurotrophin/receptor expression sites within both fetal and adult human testes. Functional assays performed with a mouse tumor Leydig cell line revealed that NGF exposure increases cellular steroid production, indicating a role in differentiation processes. These findings support previously-recognized neuronal characteristics of Leydig cells, provide additional evidence for potential roles of neurotrophins during testis morphogenesis and in the mature testis, and demonstrate for the first time a neurotrophin-induced functional activity in Leydig cells.
Müller
Dieter
D
Institute for Hormone and Fertility Research, University of Hamburg, Falkenried 88, 20251 Hamburg, Germany.
Davidoff
Michail S
MS
Bargheer
Oliver
O
Paust
Hans-J
HJ
Pusch
Wolfgang
W
Koeva
Yvetta
Y
Jezek
Davor
D
Holstein
Adolf F
AF
Middendorff
Ralf
R
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D011374:Progesterone; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; C073922:neurotrophin 4