Modification of luteinizing hormone secretion by activators of Ca2+/phospholipid-dependent protein kinase.
We investigated the role of Ca2+/phospholipid-dependent protein kinase (protein kinase C) in LH secretion using rat anterior pituitary pieces obtained at known stages of the estrous cycle and superfused in vitro. Secretagogues were administered as 10-min (LHRH) or 30-min (all others) pulses. Activation of protein kinase C with phorbol 12-myristate 13-acetate (PMA) results 2 h later in an amplification of LHRH-induced LH secretion in a concentration (1 nM to 1 microM)-and protein synthesis-dependent manner in proestrous, but not estrous, pituitaries; the diacylglycerol analog 1-oleoyl-2-acetylglycerol (OAG) also augments subsequent LHRH-induced secretion. At 1 microM, PMA alone increases the LH secretory rate, but with a pattern different from that induced by LHRH; the characteristics of the PMA response are affected by prior exposure to LHRH, estrous cycle stage, and cycloheximide. Pretreatment with either 8-bromo-cAMP or forskolin results in augmentation of subsequent LHRH-induced secretion without affecting baseline secretion. If the cells are exposed simultaneously to forskolin and OAG, but not 8-bromo-cAMP and OAG, the augmentation is dampened. This preliminary result suggests a possible interaction between protein kinase C and cAMP-dependent protein kinase in LH secretion regulation. We conclude that, regarding initiation of LH release, protein kinase C appears to be but one of a complex of mediators required for the secretory response to LHRH. Regarding the amplification of LHRH-induced release, activation of protein kinase C may be a component of the LHRH self-priming response.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004971:Estrus; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D010743:Phospholipids; D007987:Gonadotropin-Releasing Hormone; C038237:1-oleoyl-2-acetylglycerol; D007986:Luteinizing Hormone; D003513:Cycloheximide; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium