Stimulation of Luteinizing Hormone-Beta Messenger Ribonucleic Acid and Post-Translational Modification of Luteinizing Hormone Isoforms by Second Messengers Mediating the Action of Gonadotrophin-Releasing Hormone

Several second messenger systems have been implicated in mediating the action of gonadotrophin-releasing hormone on the pituitary gonadotrophs and numerous studies have shown that activation of these systems induces luteinizing hormone (LH) secretion. However, it is not known how gonadotrophin-releasing hormone or the second messenger systems induce de novo LH biosynthesis and post-translational modification of the hormone. In these experiments hemipituitary glands have been perifused with drugs which activate second messengers or stimulate protein kinase C directly. The LH secretory responses have been correlated with measurements of common a and LHβ mRNA and the molecular species of LH which were present in the pituitary perifusate after exposure to the drugs. Gonadotrophin-releasing hormone (50 ng/ml, 42 nM), with and without the presence of extracellular Ca²⁺, the Ca²⁺ ionophore, A23187 (10 μM), and phorbol 12-myristate (1 μM) all stimulated an increase in LHβ mRNA compared with controls and the appearance of a different isoform of LH to that found stored in and released from the unstimulated pituitary gland. Phospholipase C was without effect on LHβ mRNA levels and showed minimal efficacy in inducing the appearance of the different LH isoform.