title: cAMP and protein kinase C elevate LH beta mRNA levels by activating transcription rather than stabilizing mRNA in rat pituitary cells.
abstract: The mechanisms by which GnRH modulates synthesis of LH beta subunit and release of LH from the pituitary gonadotropes are not clearly understood. However, GnRH actions in the pituitary gonadotropes have been suggested to be mediated by the PKC- and/or cAMP-dependent pathways. Thus, in the present study we have examined 1) whether the activations of either the PKC- and/or cAMP-dependent signaling cascades could elevate the levels of LH beta mRNA, and if so, 2) whether this increase of LH beta mRNA levels is the result of transcriptional activation or the result of suppressing the turnover of LH beta mRNA. In the present experiment, the activators of protein kinase C and the adenylate cyclase, PMA (5 nM) and forskolin (10 microM) respectively, have elevated the steady state levels of LH beta mRNA significantly by 18 h at the specific concentrations shown in the parenthesis. Subsequently, we have determined whether the elevation of LH beta mRNA levels by either PMA or forskolin is due to the new synthesis of LH beta mRNA or the suppression of LH beta mRNA turnover. Result showed that the ability of PMA or forskolin to elevate the LH beta mRNA levels was suppressed by the addition of actinomycin D, an inhibitor of transcription. Result further showed that the turnover of LH beta mRNA was not suppressed either by PMA or forskolin. These results indicate that the activation of PKC as well as the elevation of cAMP by GnRH leads to the increase in the levels of LH beta mRNA by stimulating the new synthesis of LH beta mRNA instead of increasing the stability of pre-existing LH beta mRNA.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: D
authors.initials: D
authors.lastname: Park
authors.forename: C
authors.initials: C
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Cheon
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Ryu
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000235:genetics*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: D012333:RNA, Messenger; D005576:Colforsin; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate