Gonadotropin-releasing hormone and the control of gonadotrope function.
Normal gametogenesis and steroidogenesis is highly dependent on the pulsatile release of hypothalamic GnRH that binds high-affinity receptors present at the surface of pituitary gonadotrophs thereby triggering the synthesis and release of the gonadotropins LH and FSH. The mammalian GnRH receptor displays the classical heptahelical structure of G protein-coupled receptors with, however, a unique feature, the lack of a C-terminal tail. Accordingly, it does not desensitise sensu stricto, and internalises very poorly. It is now well established that GnRH stimulation induces the activation of a complex network of transduction pathways involved in the control of gonadotropin release and subunit gene expression. Other authors and ourselves have demonstrated that the GnRH action is associated with an increased complexity regarding gene regulation/cell function. Indeed GnRH affects the GnRH receptor gene itself and a number of additional genes that include some involved in cell signalling and auto-/paracrine regulation. The fact that GnRH regulates the expression of its own receptor, together with a host of other genes typically involved in its signal transduction cascades implies alteration/auto-adaptation in gonadotropic responsiveness. Furthermore, some of these genes respond differentially depending on whether the GnRH stimulation is intermittent or permanent suggesting specific roles in the dual process of activation/desensitisation. Thus, it can be assumed that the importance of pulsatility of GnRH action is closely related to, or dependent on, the inability of the GnRH receptor to desensitise. Moreover, multiple post-receptor events are crucial for both the regulation/plasticity of gonadotropic function and the maintenance of cell integrity.
Counis
Raymond
R
Physiologie de l,axe gonadotrope, UMR-CNRS 7079, Université Pierre et Marie Curie, Paris, France. Raymond.counis@snv.jussieu.fr
Laverrière
Jean-Noël
JN
Garrel
Ghislaine
G
Bleux
Christian
C
Cohen-Tannoudji
Joëlle
J
Lerrant
Yannick
Y
Kottler
Marie-Laure
ML
Magre
Solange
S
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D006065:Gonadotropins, Pituitary / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism* / Q000502:physiology; D011966:Receptors, LHRH / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D006065:Gonadotropins, Pituitary; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone