EGF stimulates rat spermatogonial DNA synthesis in seminiferous tubule segments in vitro.
Epidermal growth factor (EGF) superfamily of peptide growth factors (EGF-GFs) plays a role in male germ cell development, but the precise function is yet to be defined. The present study shows that EGF-GFs stimulate spermatogonial proliferation in vitro. The EGF-GF ligands, EGF, transforming growth factor-alpha and betacellulin all stimulated DNA synthesis in microdissected stage I segments of rat testis seminiferous tubules in vitro, as revealed by 3H-thymidine incorporation and 5-bromo-2'-deoxyuridine (BrdU) labeling. A fourfold increase over control of BrdU labeled cells, identified as spermatogonia, was seen after treatment with EGF. RT-PCR analysis revealed that the EGF receptors erbB1, erbB2, erbB3 and erbB4 were expressed at all stages of the spermatogenic wave, whereas differential expression was found in isolated Leydig, Sertoli and peritubular cells. The results show that EGF-GFs is spermatogonial growth factor(s) in vitro, although we have not discriminated between a direct action and an indirect effect via somatic cells. We suggest that EGF-GFs is involved in the paracrine control of spermatogenesis in vivo.
Wahab-Wahlgren
Aida
A
Pediatric Endocrinology Unit, Q2:08, Department of Woman and Child Health, Astrid Lindgren Children's Hospital, Karolinska Institute and Hospital, S-171 76 Stockholm, Sweden. aida.wahlgren@kbh.ki.se
Martinelle
Nina
N
Holst
Mikael
M
Jahnukainen
Kirsi
K
Parvinen
Martti
M
Söder
Olle
O
D000818:Animals; D066259:Betacellulin; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D066247:Receptor, ErbB-4; D011994:Recombinant Proteins / Q000494:pharmacology; D012671:Seminiferous Tubules / Q000187:drug effects* / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D013093:Spermatogonia / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D066259:Betacellulin; D001973:Bromodeoxyuridine; D004247:DNA; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D011994:Recombinant Proteins; D013936:Thymidine; D016211:Transforming Growth Factor alpha; C587853:Btc protein, rat; C587691:Erbb4 protein, rat