The GnRH receptor and the response of gonadotrope cells to GnRH pulse frequency code. A story of an atypical adaptation of cell function relying on a lack of receptor homologous desensitization.

Brain control of the reproductive system is mediated through hypothalamic gonadotropin-releasing hormone (GnRH) which activates specific receptors (GnRHR) present at the surface of the pituitary gonadotropes to trigger secretion of the two gonadotropins LH and FSH. A unique feature of this system is the high dependence on the secretion mode of GnRH, which is basically pulsatile but undergoes considerable fluctuations in pulse frequency pattern in response to endogenous or external factors. How the physiological fluctuations of GnRH secretion that orchestrate normal reproduction are decoded by the gonadotrope cell machinery to ultimately control gonadotropin release and/or subunit gene transcription has been the subject of intensive studies during the past decades. Surprisingly, the mammalian GnRHR is unique among G protein-coupled receptor family as it lacks the carboxy-terminal tail usually involved in classical endocytotic process. Accordingly, it does not desensitize properly and internalizes very poorly. Both this atypical intrinsic property and post-receptor events may thus contribute to decode the GnRH signal. This includes the participation of a network of signaling pathways that differently respond to GnRH together with a growing amount of genes differentially sensitive to pulse frequency. Among these are two pairs of genes, the transcription factors EGR-1 and NAB, and the regulatory factors activin and follistatin, that function as intracellular autoregulatory feedback loops controlling respectively LHbeta and FSHbeta gene expression and hence, LH and FSH synthesis. Pituitary gonadotropes thus represent a unique model of cells functionally adapted to respond to a considerably fluctuating neuroendocrine stimulation, from short individual pulses to sustained GnRH as observed at the proestrus of ovarian cycle. Altogether, the data emphasize the adaptative reciprocal complementarity of hypothalamic GnRH neurones and pituitary gonadotropes to function as an original unit

Expression of GnRH receptor during functional maturation of pituitary gonadotropes and testicular Leydig cells

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Régulation neurohormonale de l'activité et de l'expression de la NO synthase de type I et identification de canaux cibles de cette nouvelle voie de signlisation dans la cellule gonadotrope hypophysaire

Afin de rechercher une implication physiologique à la NO synthase (NOS 1) récemment identifiée dans la cellule gonadotrope, nous avons suivi les niveaux d'enzyme et de GMPc hypophysaires au cours du cycle oestrien chez la ratte et montré leur élévation importante, transitoire et GnRH-dépendante au pro-oestrus. "In vitro" (cellule antéhypophysaires en culture) nous avons retrouvé les effets stimulants de la GnRH sur l'expression de NOS I et la production de GMPc et caractérisé ceux d'un autre peptide hypophysiotrope, le PACAP. Enfin, nous avons montré la présence (ARNm et/ou protéines) des sous-unités de canaux CNG (cyclic nucleotide-gated channels) dans les cellules gonadotropes du rat normal et castré et démontré en "patch-clamp" leur fonctionalité. L'ensemble argue en faveur d'un rôle de NOS I et du GMPc dans la signalisation de la GnRH et du PACAP et dans le fonctionnement de la cellule gonadotrope avec une contribution des canaux CNG à l'excitabilité cellulaire et aux flux de calcium.To evaluate the physiological implication of the neuronal type nitric oxide synthase (NOS I) recently identified in gonadotrophs we determined the pituitary levels of this enzyme and of cGMP during the estrus cycle in the female rat thus demonstrating their marked, transient and GnRH-dependent increase at pro-estrus. "In vitro" (cultured anterior pituitary cells) a stimulatory effect of GnRH was similarly observed on NOS I expression and cGMP production whereas the effects of another hypophysiotropic peptide, PACAP, were characterized. Finally, we demonstrated the presence (mRNA and protein) of cyclic nucleotide-gated (CNG) channel subunits (olfactory and retinal type) in gonadotrophs of intact and castrated rat that appeared functional using patch-clamp analysis. Altogether, data argue in favor of a role of NOS I and cGMP in the GnRH and PACAP signaling as well as in the physiology of gonadotrophs with a specific contribution of CNG channels to cell excitability and calcium fluxes.PARIS5-BU Saints-Pères (751062109) / SudocSudocFranceF

La sécrétion des hormones gonadotropes hypophysaires et sa régulation

Chapitre 10absen

Insect cells infected with a recombinant baculovirus express both O- and N-glycosylated forms of the rat glycoprotein hormone alpha-subunit

International audienc

Régulation de la synthèse et de la libération des gonadotropines hypophysaires

chap. 3National audienc

Localization of luteinizing hormone betamRNA by in situ hybridization in the sheep pars tuberalis

International audienc

Le système baculovirus ; étude des relations structure-fonction des hormones glycoprotéiques hypophysaires

National audienc