[Mechanism of action of gonadoliberin in pituitary gonadotropic cells].
The gonadotropin-releasing hormone (GnRH) controls LH and FSH secretion by membrane receptor interaction followed by a transmission mechanism involving Ca2+ secretion and phosphoinositides hydrolysis. In the first step, GnRH binds to its receptor and induces the formation of aggregates of a certain number of hormone-receptor complexes. Some of these GnRH-receptor complexes are internalized. Then, the receptors are either degraded in lysosomes or recycled through inclusion into secretory granules in the area of the Golgi. Note that receptor internalization is not necessary for the LH response to GnRH that intervenes immediately after GnRH binding to its receptor. Binding of GnRH to membrane receptors provokes extracellular calcium flux into the cell. At the same time, an increase in intracellular Ca2+ from non-mitochondrial stock is observed. Intracellular Ca2+ is important for the initiation of LH response and then extracellular Ca2+ is necessary for a sustained response. GnRH also stimulates phosphoinositides hydrolysis (probably mediated by a G-protein) inducing inositol 1,4,5-triphosphate liberation. This component would participate in Ca2+i increase necessary for the early LH response. Another hydrolysis product is diacylglycerol (DAG) that binds principally to protein kinase C (PKC). On the one hand, this complex can activate "masked" GnRH receptors and participate in this manner to an up-regulation. On the other hand, it seems that FSH beta mRNA expression depends on PKC. GnRH secretion rythm modulates alpha, LH beta and FSH beta subunits mRNA expression, and secretion of these hormones. PKC could be an important regulator of these functions. DAG can also induce LH secretion, this mechanism uses PKC activation and requires gonadotrophin neosynthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Arsenijevic
Y
Y
Division de Biologie de la Croissance et de la Reproduction, Université de Genève Faculté de Médecine, Suisse.
Aubert
M L
ML
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000502:physiology; D004075:Diglycerides / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000737:chemistry / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism
D004075:Diglycerides; C029152:G-substrate; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D011493:Protein Kinase C; D002118:Calcium
Mécanismes d'action de la gonadolibérine au niveau des cellules gonadotropes hypophysaires.