Luteinizing Hormone-Induced Extracellular-Signal Regulated Kinase Activation Differently Modulates Progesterone and Androstenedione Production in Bovine Theca Cells

• Published in: Endocrinology (Philadelphia) 2005-07, Vol.146 (7), p.2903-2910
• Main Authors: Tajima, Kimihisa, Yoshii, Kumiko, Fukuda, Shin, Orisaka, Makoto, Miyamoto, Kaoru, Amsterdam, Abraham, Kotsuji, Fumikazu
• Format: Article
• Language: English
• Subjects: Androstenedione; Androstenedione - biosynthesis; Animals; Biological and medical sciences; Butadienes - pharmacology; Cattle; Cell activation; Colforsin - pharmacology; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Enzyme Activation - physiology; Enzyme Inhibitors - pharmacology; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Fibroblast Growth Factor 2 - pharmacology; Forskolin; Fundamental and applied biological sciences. Psychology; Gonadotropins; Granulosa cells; Intracellular; Isoquinolines - pharmacology; Kinases; Luteinizing hormone; Luteinizing Hormone - pharmacology; MAP kinase; MEK inhibitors; Modulation; mRNA; Nitriles - pharmacology; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphoric Monoester Hydrolases - antagonists & inhibitors; Phosphorylation; Phosphorylation - drug effects; Pituitary (anterior); Progesterone; Progesterone - biosynthesis; Protein kinase A; Protein kinase A inhibitors; Protein Kinase Inhibitors - pharmacology; Proteins; RNA, Messenger - metabolism; Steroid 17-alpha-Hydroxylase - genetics; Steroidogenesis; Steroidogenic acute regulatory protein; Sulfonamides - pharmacology; Tetradecanoylphorbol Acetate - pharmacology; Theca; Theca Cells - drug effects; Theca Cells - metabolism; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2005-0093

It has been reported that gonadotropins promoted phosphorylation of ERK/MAPK in granulosa cells. However, little is known about the effects of gonadotropin on ERK activity in theca cells. This study explores how LH/forskolin controls ERK phosphorylation in cultured bovine theca cells. Effects of ERK on steroidogenesis were also investigated. Phosphorylation of ERK in bovine theca cells was augmented by LH and forskolin in 5 min; it decreased thereafter below basal levels in 20 min. Nevertheless, phosphorylation of the ERK kinase, MEK, was unaffected. Addition of H89 (a protein kinase A inhibitor) significantly reduced the effect of LH/forskolin on ERK phosphorylation. A potent MEK inhibitor PD98059 eliminated ERK phosphorylation and augmented progesterone production concomitantly with the elevation of intracellular steroidogenic acute regulatory protein mRNA in LH/forskolin-stimulated theca cells. In contrast to progesterone production, androgen production was diminished significantly by inhibition of ERK with decreased intracellular P450c17 mRNA levels. Taking these results together, we conclude that LH/cAMP leads to phosphorylation of ERK in a biphasic manner through MEK-independent pathway in bovine theca cells. Protein kinase A-induced phosphatase could possibly contribute to the phosphorylation process. Furthermore, modulation of ERK phosphorylation involves control of thecal steroidogenesis via modulation of the expression of steroidogenic acute regulatory protein and P450c17.