-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.

No abstract

It was previously established that the administration of a potent GnRH agonist such as triptorelin (D-Trp6-GnRH) induced desensitization of pituitary gonadotropic cells, resulting in decreased expression of gonadotropin beta-subunit genes and the suppression of LH and FSH synthesis and release. Binding of GnRH to the pituitary is also affected by agonist treatment. To examine the desensitizing effects of GnRH agonist on the expression of the pituitary GnRH receptor (GnRH-R) gene, male rats were given triptorelin (long-acting formulation, 300 micrograms/kg), and levels of GnRH-R messenger RNA (mRNA) were determined by Northern and dot blot hybridization to a 32P-labeled rat complementary DNA probe. Abundances of gonadotropin alpha-subunit, LH beta, and FSH beta mRNAs were examined in parallel, using appropriate probes. A rapid time-dependent decrease in the level of GnRH-R mRNA was observed in rats after triptorelin administration. A minimum residual level of mRNA, in the range of 20-25% of the initial value, was attained as early as 5 h after treatment. Levels further stabilized to 25-30% after a small transient increase to 45% on day 5. A single injection was effective for at least 30 days, after which GnRH-R mRNA levels slowly returned to normal, suggesting a progressive abolition of agonist effects. A concomitant acute depletion of mRNA levels was observed for LH beta and FSH beta (50% decrease in about 48 and 3 h, respectively), whereas the alpha-subunit message increased (rapidly reaching a level 1.8-fold that in control rats after 1-2 days). Castration induced a 3.8-fold elevation in the amounts of GnRH-R mRNA after 3 weeks, whereas alpha, LH beta, and FSH beta mRNAs increased by 6.2-, 7.9-, and 4.2-fold, respectively, compared to corresponding values in intact animals. Administration of the GnRH agonist readily prevented, for as long as 3 weeks, the stimulatory effects of castration on the GnRH-R mRNA and mRNAs for the beta-subunit of gonadotropins, but not for the alpha mRNA, which remained at a high level. When triptorelin was administered 3 weeks postoperatively, the castration-induced increase in LH beta and FSH beta was totally abolished, and no significant effect was noted on alpha-subunit mRNA. In conclusion, these data demonstrate that expression of the GnRH-R gene is subject to regulation and depends on GnRH stimulation, in a manner that indicates susceptibility to desensitizing action by the long-acting GnRH analog, triptorelin.(ABSTRACT TRUNCATED AT 400 WORDS)

This cross-sectional study assessed sugar-sweetened beverage (SSB) consumption and its associations with the sociodemographic and physical characteristics, behavior and knowledge of New Caledonian adolescents. The survey data of 447 adolescents from ages 11 to 16 years were collected in five secondary public schools of New Caledonia between July 2015 and April 2016. These data included measured height and weight, SSB consumption, sociodemographic characteristics, body weight perception, physical activity, and knowledge (sugar quantity/SSB unit; energy expenditure required to eliminate a unit) and opinions about the SSB‒weight gain relationship. Ninety percent of these adolescents declared regularly drinking SSBs. Quantities were associated with living environment (1.94 L·week−1 in urban environment vs. 4.49 L·week−1 in rural environment, p = 0.001), ethnic community (4.77 L·week−1 in Melanesians vs. 2.46 L·week−1 in Caucasians, p < 0.001) and knowledge about energy expenditure (6.22 L·week−1 in unknowledgeable adolescents vs. 4.26 L·week−1 in adolescents who underestimated, 3.73 L·week−1 in adolescents who overestimated, and 3.64 L·week−1 in adolescents who correctly responded on the energy expenditure required to eliminate an SSB unit, p = 0.033). To conclude, community-based health promotion strategies should (1) focus on the physical effort needed to negate SSB consumption rather than the nutritional energy from SSB units and (2) highlight how to achieve sustainable lifestyles and provide tools for greater understanding and positive action.

Several factors are associated with overweight status in New Caledonian adolescents. Breakfast education should be improved for adolescents living in rural areas and from low socioeconomic status.

BackgroundAdolescent obesity is prevalent in Pacific region ethnic groups (European, Melanesian and Polynesian) living in both urban and rural areas. Although body perception is an important factor of weight gain or loss, little is known about the body self-perceptions of Pacific region adolescents. This study therefore evaluated adolescent perceptions of body weight according to ethnicity (European, Melanesian or Polynesian), socioeconomic status (low, intermediate or high) and living area (rural or urban) in New Caledonia.MethodsSociodemographic and anthropomorphic data from 737 adolescents (351 boys and 386 girls) with ages ranging from 11 to 16 years were collected and analysed. The International Obesity Task Force (IOTF) standards were used to define weight status as normal-weight, underweight or overweight/obese. Weight perception was assessed from detailed questionnaires, with adolescents rating their own weight with the following descriptors: ‘about the right weight’, ‘too heavy’, or ‘too light’.ResultsResults showed that only 8.5% of normal-weight adolescents (7% boys and 10% girls) identifying themselves as ‘too heavy’. Normal-weight Melanesian adolescents were less likely than their European counterparts to assess themselves as too heavy (OR = 0.357). However, half the overweight/obese adolescents underestimated their weight status (53% boys and 48% girls). Weight misperception was associated with ethnicity, socioeconomic status and living area, with gender-specific differences.ConclusionsThe results of this study suggest that these sociodemographic factors should be taken into account when designing public health policies and health education school programmes in New Caledonia and, more broadly, the Pacific region.

Previous studies have established that the interaction of gonadotropin-releasing hormone (GnRH) with its receptor (GnRHR) would require partial entry of the N- and C-terminal regions of ligand into the transmembrane core. The functional significance of the conserved aromatic residue Trp(279) present in the transmembrane helix 6, and Val(299) located in exoloop 3 of the rat GnRHR was investigated by mutagenesis followed by expression in Chinese hamster ovary-K1 cells. Compared with wild-type, substitution of Trp(279) with Ser or Arg resulted in a marked reduction or total abolition, respectively, of ligand binding and, in both cases, abrogation of GnRH-induced inositol phosphate production. A total absence of functionality was observed when Val(299) was simply replaced with Ala. Mention should be made that an expression of all mutated and wild-type receptor proteins was observed. Interestingly, the double mutant [Trp(279)Arg/Val(299)Ala]GnRHR restored B(max) to wild type (504 +/- 43 versus 541 +/- 41 fmol/mg protein), but with a diminished affinity (4.95 +/- 1.05 versus 0.94 +/- 0.35 nM), and GnRH failed to induce inositol phosphate. No influence of the mutations was seen on internalization of the receptor. The three-dimensional model of GnRH binding to the rat GnRHR was built predicting that Trp(279) is buried at 20 A in the transmembrane core of the receptor, directly in contact with Trp(3) of GnRH. In contrast, Val(299) is located in a region that cannot be precisely defined at the extracellular end of transmembrane helix 7. Although models cannot provide any clue concerning the observed interactivity between the two distal residues, altogether these data reveal the functional importance of both GnRHR Trp(279) and Val(299) and suggest that Trp(279), interacting with GnRH Trp(3), represents the bottom of the binding pocket.

This study shows that Melanesian adolescents have lower %BF than their European counterparts for the same BMI z score. Therefore, the diagnostic accuracy of BMI to detect overfatness is related to ethnicity. Whatever the BMI-based reference, sensitivity was higher in the Melanesian group, while specificity was higher in the European group.