Autocrine regulation of steroidogenic function of Leydig cells by transforming growth factor-alpha.
We have determined the effects of LH on the expression of transforming growth factor-alpha (TGFalpha) and epidermal growth factor receptor (EGFR) system in rat Leydig cells and investigated its role in steroidogenesis. LH and TGFalpha/epidermal growth factor (EGF) significantly increased the levels of TGFalpha mRNA and protein, and the levels of EGFR protein in immature rat Leydig cells (ILC). Treatment with TGFalpha or EGF for 24h resulted in significant increase in androgen production in ILC. The increase in androgen production in response to TGFalpha was associated with increased mRNA levels of SR-BI, steroidogenic acute regulatory (StAR) and P450scc but not of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and P450c17. TGFalpha also caused a marked increase in the levels StAR protein in ILC. EGFR inhibitor (AG1478) blocked the effects of TGFalpha while MEK-inhibitor (PD98059) potentiated TGFalpha or LH effects on steroidogenesis. A PKA inhibitor (H89) blocked both TGFalpha and LH effects on steroidogenesis. We conclude that TGFalpha plays an autocrine role in LH dependent development and function of Leydig cells.
Millena
Ana Cecilia
AC
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Reddy
Sheila C
SC
Bowling
Gretchen H
GH
Khan
Shafiq A
SA
D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D019898:Autocrine Communication; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D007546:Isoquinolines / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007986:Luteinizing Hormone / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D011799:Quinazolines; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D013256:Steroids / Q000096:biosynthesis*; D013449:Sulfonamides / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D020032:Tyrphostins / Q000494:pharmacology; D000098682:Steroidogenic Acute Regulatory Protein
D000728:Androgens; D005419:Flavonoids; D007546:Isoquinolines; D010750:Phosphoproteins; D011799:Quinazolines; D012333:RNA, Messenger; D013256:Steroids; D013449:Sulfonamides; D016211:Transforming Growth Factor alpha; D020032:Tyrphostins; D000098682:Steroidogenic Acute Regulatory Protein; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one