Epidermal growth factor mediates spermatogonial proliferation in newt testis.
The complex processes of spermatogenesis are regulated by various factors. The aim of the current study is to determine the effect of epidermal growth factor (EGF) on spermatogonial proliferation and clarify the mechanism causing the proliferation in newt testis. In the organ culture, EGF stimulated spermatogonial proliferation, but not their differentiation into spermatocytes. cDNA cloning identified 3 members of the EGF receptors, ErbB1, ErbB2, and ErbB4, in the testis. RT-PCR showed that all the receptors cloned were expressed in both Sertoli and germ cells at the spermatogonial stage. In the organ cultures with inhibitors for the EGF receptors, mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K), the EGF-induced spermatogonial proliferation was suppressed. Furthermore, when the organ culture was exposed to EGF, the expressions of stem cell factor (SCF), immunoglobulin-like domain containing neuregulin1 (Ig-NRG1), and ErbB4 mRNA were increased. These results suggested that, since the spermatogonia are sequestered within cysts by the blood-testis barrier consisted of Sertoli cells, EGF possibly mediates spermatogonial proliferation in an endocrine manner through the receptors including ErbB1, ErbB2, and ErbB4 expressed on Sertoli cells via activation of MAPK cascade or/and PI3K cascade by elevating the expressions of SCF, Ig-NRG1, and ErbB4.
Abé
Keisuke
K
Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555, Japan. abeshin@gpo.kumamoto-u.ac.jp
Eto
Ko
K
Abé
Shin-ichi
S
D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D018734:Genes, erbB-2 / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D020890:Neuregulin-1 / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D066247:Receptor, ErbB-4; D012455:Salamandridae / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013093:Spermatogonia / Q000187:drug effects* / Q000502:physiology; D019089:Stem Cell Factor / Q000235:genetics; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D020890:Neuregulin-1; D019089:Stem Cell Factor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D066247:Receptor, ErbB-4