Expression of the TGF-beta1 system in human testicular pathologies.
BACKGROUND
In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO) and hypospermatogenesis (H) are commonly found. In these pathologies, Leydig cell hyperplasia (LCH) is detected in some patients. Since TGF-β1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), and the co-receptor endoglin in human biopsies from patients with idiopathic infertility.


METHODS
Specific immunostaining of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), co-receptor endoglin and Smads proteins, were carried out in testicular biopsies from normal and infertile men with SCO or H. Gene expression of TGF-β1 system were made in biopsies from infertile patients with semi-quantitative and quantitative PCR.


RESULTS
Immunohistochemical studies revealed that TGF-β1 and its specific receptors are present in Leydig cells in biopsies from normal tissue or patients with SCO or H with or without LCH. Smad proteins, which are involved in TGF-β1 signaling, are also detected in both their phosphorylated (activated) and dephosphorylated form in all samples TGF-β1, ALK-1 and endoglin gene expression are stronger in human biopsies with LCH than in those with SCO or H. Neither TGFBRII nor ALK-5 gene expression showed significant differences between pathologies. A significant correlation between ALK-1 and endoglin expression was observed.


CONCLUSIONS
In conclusion, the high levels of mRNA and protein expression of the TGF-β1 system in patients with LCH, particularly ALK1 and its correlation with endoglin, suggest that these proteins acting in concert might be, at least in part, committed actors in the Leydig cell hyperplasia.
Instituto de Biología y Medicina Experimental (CONICET), Vuelta de Obligado 2490 (1428) Buenos Aires, Argentina.
Candela R
CR
Gonzalez
María E
ME
Matzkin
Mónica B
MB
Frungieri
Claudio
C
Terradas
Roberto
R
Ponzio
Elisa
E
Puigdomenech
Oscar
O
Levalle
Ricardo S
RS
Calandra
Silvia I
SI
Gonzalez-Calvar
D030301:Activin Receptors, Type II / Q000096:biosynthesis; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D000071063:Endoglin; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D007248:Infertility, Male / Q000378:metabolism*; D007985:Leydig Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D054331:Sertoli Cell-Only Syndrome / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism; D013733:Testicular Diseases / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human