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In order to evaluate the role of Src tyrosine kinase in thecal cell steroidogenesis, a pharmacological approach was utilized by treating enriched populations of mouse ovarian theca-interstitial cells in vitro with a direct Src kinase inhibitor, PP2. Inhibition of Src with PP2 increased both basal and forskolin-stimulated androstenedione secretion, and increased cytochrome P450 17-alpha hydroxylase-lyase (CYP17) promoter activity and steady state mRNA. PP2 did not change thecal levels of StAR mRNA. Inhibition of mitogen-activated protein kinase kinase, a downstream regulator of Src activity, using PD98059 also increased forskolin-stimulated secretion of androstenedione above forskolin alone, but had no effect on basal secretion of androstenedione. Src inhibition increased mitogen-activated protein kinase phosphatase-1 protein and decreased phosphorylation of SF-1, which correlated with increased CYP17 promoter activity and mRNA levels. These results implicate Src tyrosine kinase in the regulation of CYP17 and thecal androgen secretion.

Titel:	The Src tyrosine kinase pathway regulates thecal CYP17 expression and androstenedione secretion.
Autor/in / Beteiligte Person:	Chaturvedi, G ; Arai, K ; Terranova, PF ; Roby, KF
Link:	Full Text Finder (Volltext)
Zeitschrift:	Molecular and cellular biochemistry, Jg. 318 (2008-11-01), Heft 1-2, S. 191-200
Veröffentlichung:	New York : Springer ; <i>Original Publication</i>: The Hague, Dr. W. Junk B. V. Publishers., 2008
Medientyp:	academicJournal
ISSN:	0300-8177 (print)
DOI:	10.1007/s11010-008-9871-9
Schlagwort:	Animals Cholesterol Side-Chain Cleavage Enzyme genetics Cholesterol Side-Chain Cleavage Enzyme metabolism Colforsin pharmacology Cyclic AMP metabolism Dual Specificity Phosphatase 1 genetics Dual Specificity Phosphatase 1 metabolism Female Flavonoids pharmacology MAP Kinase Kinase 1 antagonists & inhibitors Mice Mice, Inbred C57BL Phosphoproteins genetics Phosphoproteins metabolism Promoter Regions, Genetic Pyrimidines pharmacology Steroid 17-alpha-Hydroxylase genetics Steroidogenic Factor 1 genetics Steroidogenic Factor 1 metabolism Theca Cells drug effects src-Family Kinases antagonists & inhibitors Androstenedione metabolism Steroid 17-alpha-Hydroxylase metabolism Theca Cells enzymology Theca Cells metabolism src-Family Kinases metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Mol Cell Biochem] 2008 Nov; Vol. 318 (1-2), pp. 191-200. <i>Date of Electronic Publication: </i>2008 Jul 19. MeSH Terms: Androstenedione / metabolism ; Steroid 17-alpha-Hydroxylase / metabolism ; Theca Cells / enzymology ; Theca Cells / metabolism ; src-Family Kinases / *metabolism ; Animals ; Cholesterol Side-Chain Cleavage Enzyme / genetics ; Cholesterol Side-Chain Cleavage Enzyme / metabolism ; Colforsin / pharmacology ; Cyclic AMP / metabolism ; Dual Specificity Phosphatase 1 / genetics ; Dual Specificity Phosphatase 1 / metabolism ; Female ; Flavonoids / pharmacology ; MAP Kinase Kinase 1 / antagonists & inhibitors ; Mice ; Mice, Inbred C57BL ; Phosphoproteins / genetics ; Phosphoproteins / metabolism ; Promoter Regions, Genetic ; Pyrimidines / pharmacology ; Steroid 17-alpha-Hydroxylase / genetics ; Steroidogenic Factor 1 / genetics ; Steroidogenic Factor 1 / metabolism ; Theca Cells / drug effects ; src-Family Kinases / antagonists & inhibitors References: Mol Reprod Dev. 2004 Jul;68(3):335-44. (PMID: 15112327) ; J Mol Endocrinol. 2001 Jun;26(3):207-15. (PMID: 11357057) ; Reprod Nutr Dev. 2005 Jan-Feb;45(1):101-8. (PMID: 15868656) ; Biol Reprod. 2002 Sep;67(3):789-94. (PMID: 12193386) ; J Biol Chem. 1995 Oct 13;270(41):24585-8. (PMID: 7592678) ; Mol Cell Biol. 2000 Dec;20(23):9018-27. (PMID: 11074000) ; Endocrine. 2004 Nov;25(2):147-54. (PMID: 15711029) ; J Clin Endocrinol Metab. 2007 Dec;92(12):4802-9. (PMID: 17895316) ; Mol Endocrinol. 1996 Feb;10(2):147-58. (PMID: 8825555) ; J Biol Chem. 2003 Mar 7;278(10):8106-11. (PMID: 12506119) ; Hypertension. 2001 Jul;38(1):56-64. (PMID: 11463760) ; J Mol Endocrinol. 2003 Jun;30(3):287-99. (PMID: 12790800) ; Endocrinology. 2000 Apr;141(4):1545-53. (PMID: 10746662) ; J Clin Endocrinol Metab. 2001 Jan;86(1):375-80. (PMID: 11232027) ; Br J Cancer. 2002 Oct 21;87(9):1000-5. (PMID: 12434292) ; Cell. 1990 Aug 10;62(3):481-92. (PMID: 1696179) ; Mol Endocrinol. 2005 Feb;19(2):379-90. (PMID: 15514033) ; Oncogene. 2004 Oct 18;23(48):7957-68. (PMID: 15489913) ; J Biol Chem. 2005 Mar 18;280(11):10253-63. (PMID: 15637050) ; Annu Rev Cell Dev Biol. 1997;13:513-609. (PMID: 9442882) ; J Biol Chem. 1986 Jun 25;261(18):8429-33. (PMID: 3487544) ; Endocr Res. 2002 Nov;28(4):551-8. (PMID: 12530662) ; Mol Endocrinol. 2004 Apr;18(4):791-806. (PMID: 14726488) ; J Endocrinol. 2005 Nov;187(2):267-74. (PMID: 16293774) ; Endocrinology. 1996 Dec;137(12):5735-8. (PMID: 8940409) ; Endocrinology. 2002 Jan;143(1):295-303. (PMID: 11751621) ; Mol Cell Endocrinol. 1997 Jan 3;126(1):91-100. (PMID: 9027367) ; Circ Res. 2001 Nov 23;89(11):1073-80. (PMID: 11717166) ; Invest New Drugs. 1999;17(4):361-73. (PMID: 10759403) ; Endocrinology. 2000 Aug;141(8):2895-903. (PMID: 10919277) ; J Clin Endocrinol Metab. 2000 Mar;85(3):1226-31. (PMID: 10720067) ; Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10619-23. (PMID: 7479852) ; Endocrinology. 1999 Oct;140(10):4732-8. (PMID: 10499532) ; Mol Cell Biol. 1988 Jan;8(1):497-501. (PMID: 2447487) ; Biol Reprod. 1983 Oct;29(3):630-6. (PMID: 6414543) ; DNA Cell Biol. 1994 Nov;13(11):1087-98. (PMID: 7702752) ; Cancer Cell. 2004 Sep;6(3):209-14. (PMID: 15380511) ; J Clin Endocrinol Metab. 2000 Jun;85(6):2304-11. (PMID: 10852468) ; Mol Endocrinol. 1993 Jun;7(6):776-86. (PMID: 8395654) ; J Cell Biol. 1991 Nov;115(3):809-19. (PMID: 1717492) ; Endocrinology. 2002 Apr;143(4):1280-90. (PMID: 11897684) ; Mol Biol Cell. 2001 Jul;12(7):2171-83. (PMID: 11452011) ; Endocrinology. 1995 Dec;136(12):5527-32. (PMID: 7588304) ; Mol Endocrinol. 1992 Jun;6(6):927-34. (PMID: 1323057) ; Microsc Res Tech. 2003 Jun 15;61(3):300-7. (PMID: 12768545) ; Biol Reprod. 1996 Jun;54(6):1390-6. (PMID: 8724369) ; Endocrinology. 2005 Jul;146(7):2903-10. (PMID: 15817663) ; Endocrinology. 2002 May;143(5):1769-77. (PMID: 11956159) Grant Information: P20 RR016475 United States RR NCRR NIH HHS; RR-16475 United States RR NCRR NIH HHS; P30 HD033994 United States HD NICHD NIH HHS; HD 33994 United States HD NICHD NIH HHS; U54 HD033994 United States HD NICHD NIH HHS Substance Nomenclature: 0 (AG 1879) ; 0 (Flavonoids) ; 0 (Phosphoproteins) ; 0 (Pyrimidines) ; 0 (Steroidogenic Factor 1) ; 0 (steroidogenic acute regulatory protein) ; 1F7A44V6OU (Colforsin) ; 409J2J96VR (Androstenedione) ; E0399OZS9N (Cyclic AMP) ; EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase) ; EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme) ; EC 2.7.10.2 (src-Family Kinases) ; EC 2.7.12.2 (MAP Kinase Kinase 1) ; EC 3.1.3.48 (Dual Specificity Phosphatase 1) ; EC 3.1.3.48 (Dusp1 protein, mouse) ; SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) Entry Date(s): Date Created: 20080722 Date Completed: 20081217 Latest Revision: 20211020 Update Code: 20231215 PubMed Central ID: PMC4326000

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The Src tyrosine kinase pathway regulates thecal CYP17 expression and androstenedione secretion.