Molecular mechanisms involved in LH release by the ovine pituitary cells.
The luteinizing hormone-releasing hormone (LHRH) is a hypothalamic decapeptide and main positive regulator of luteinizing hormone (LH) secretion from pituitary cells. Insulin-like growth factor-I (IGF-1) also stimulates LH release and enhances the effect of LHRH. However, the molecular mechanisms involved in the interactions between LHRH and IGF-1 are unclear. Here, we first determined the effect of various types of LHRH [I (mammalian), II (chicken), III (lamprey), hyp9 and salmon] on both LH secretion and activation of MAPK (ERK1/2 and p38) in ovine pituitary cells. After 3h of treatment, LH secretion was significantly higher for LHRH-I than for the other LHRH tested. Interestingly, LHRH-III had no effect at any concentration used on the LH release by ovine pituitary cells. The phosphorylation of both MAPK ERK1/2 and p38 was also significantly higher after treatment with LHRH-I than LHRH-II, salmon LHRH or hyp9. These MAPKs were not activated or only very weakly activated by LHRH-III. We then used pharmacological inhibitors to show that MAPK ERK1/2 and PKCdelta participate in the LH release by ovine pituitary cells in response to LHRH-I. We identified the main substrates and signaling pathways [PI3K/Akt and MAPK (ERK1/2, p38 and JNK1/2] of IGF-1R and investigated the effect of IGF-1 on the stimulation of ovine pituitary cell LH secretion by the various LHRH. IGF-1 increases LH secretion in response to LHRH-I, LHRH-II, hyp9 and salmon LHRH but not the secretion after treatment with LHRH-III. Using specific inhibitors, we found that the MAPK ERK1/2 but not the PI3K/Akt signaling pathway is involved in the LH secretion in response to IGF-1. This is the first description of a common molecular mechanism, involving the MAPK ERK1/2, by which LHRH-R and IGF-1-R induce LH secretion in ovine pituitary cells.
Yang
Dominique
D
Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Nouzilly, France.
Caraty
Alain
A
Dupont
Joëlle
J
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011966:Receptors, LHRH / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction / Q000502:physiology*
D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D020928:Mitogen-Activated Protein Kinases