Trpc2 is expressed in two olfactory subsystems, the main and the vomeronasal system of larval Xenopus laevis.

Complete segregation of the main olfactory epithelium (MOE) and the vomeronasal epithelium is first observed in amphibians. In contrast, teleost fishes possess a single olfactory surface, in which genetic components of the main and vomeronasal olfactory systems are intermingled. The transient receptor potential channel TRPC2, a marker of vomeronasal neurons, is present in the single fish sensory surface, but is already restricted to the vomeronasal epithelium in a terrestrial amphibian, the red-legged salamander (Plethodon shermani). Here we examined the localization of TRPC2 in an aquatic amphibian and cloned the Xenopus laevis trpc2 gene. We show that it is expressed in both the MOE and the vomeronasal epithelium. This is the first description of a broad trpc2 expression in the MOE of a tetrapod. The expression pattern of trpc2 in the MOE is virtually undistinguishable from that of MOE-specific v2rs, indicating that they are co-expressed in the same neuronal subpopulation.

Impact of dietary modification of advanced glycation end products (AGEs) on the hormonal and metabolic profile of women with polycystic ovary syndrome (PCOS).

OBJECTIVE: To investigate the impact of dietary intervention on Advanced Glycation End products (AGEs) intake on the hormonal and metabolic profile in women with polycystic ovary syndrome (PCOS). METHODS: After baseline evaluation, 23 women with PCOS [mean ± SD, age: 23.4 ± 5.7 years; body mass index (BMI): 26 ± 5.7 kg/m2] underwent the following consecutive 2-month dietary regimens: a hypocaloric diet with ad-libitum AGEs content (Hypo), an isocaloric diet with high AGEs (HA) and an isocaloric diet with low AGEs (LA). Metabolic, hormonal and oxidative stress status was assessed and AGEs levels were determined in all subjects after the completion of each dietary intervention. RESULTS: Serum levels of AGEs, testosterone, oxidative stress, insulin and HOMA-IR index were significantly increased on the HA compared to the Hypo diet and subsequently decreased on the LA diet (compared to HA) (p<0.05 for all parameters). BMI remained unaltered throughout the HA and LA periods compared to the Hypo period. Serum AGEs were strongly correlated with insulin, as well as with HOMA, during the LA dietary period (r=0.53, p=0.02 and r=0.51, p=0.03, respectively). For the same period, dietary AGEs were correlated with insulin levels (rho=0.49, p=0.04). CONCLUSIONS: Modifications of dietary AGEs intake are associated with parallel changes in serum AGEs, metabolic, hormonal and oxidative stress biomarkers in women with PCOS. These novel findings support recommendations for a low AGEs dietary content along with lifestyle changes in women with PCOS.

Bimodal processing of olfactory information in an amphibian nose: odor responses segregate into a medial and a lateral stream.

In contrast to the single sensory surface present in teleost fishes, several spatially segregated subsystems with distinct molecular and functional characteristics define the mammalian olfactory system. However, the evolutionary steps of that transition remain unknown. Here we analyzed the olfactory system of an early diverging tetrapod, the amphibian Xenopus laevis, and report for the first time the existence of two odor-processing streams, sharply segregated in the main olfactory bulb and partially segregated in the olfactory epithelium of pre-metamorphic larvae. A lateral odor-processing stream is formed by microvillous receptor neurons and is characterized by amino acid responses and Gαo/Gαi as probable signal transducers, whereas a medial stream formed by ciliated receptor neurons is characterized by responses to alcohols, aldehydes, and ketones, and Gαolf/cAMP as probable signal transducers. To reveal candidates for the olfactory receptors underlying these two streams, the spatial distribution of 12 genes from four olfactory receptor gene families was determined. Several class II and some class I odorant receptors (ORs) mimic the spatial distribution observed for the medial stream, whereas a trace amine-associated receptor closely parallels the spatial pattern of the lateral odor-processing stream. Other olfactory receptors (some class I odorant receptors and vomeronasal type 1 receptors) and odor responses (to bile acids, amines) were not lateralized, the latter not even in the olfactory bulb, suggesting an incomplete segregation. Thus, the olfactory system of X. laevis exhibits an intermediate stage of segregation and as such appears well suited to investigate the molecular driving forces behind olfactory regionalization.

The effect of oral micronized progesterone on hormonal and metabolic parameters in anovulatory patients with polycystic ovary syndrome.

OBJECTIVE: To investigate the effects of oral natural micronized P on hormonal and metabolic parameters in patients with polycystic ovary syndrome (PCOS) and to answer the clinical question whether induction of withdrawal bleeding is a necessity for the comparison of hormonal and metabolic data in subjects with PCOS. DESIGN: Prospective clinical study. SETTING: Academic medical center. PATIENT(S): Twenty-eight reproductive-aged women with PCOS. MAIN OUTCOME MEASURE(S): Blood sampling was collected at baseline, after 7 days of oral natural micronized P (200 mg) administration, and after withdrawal bleeding. At these three stages hormonal parameters and homeostasis assessment model (HOMA-IR) index were assessed in all patients. RESULT(S): Oral natural micronized P administration did not alter significantly insulin sensitivity index and androgen levels; however, LH was decreased when postbleeding values were compared to baseline. Nevertheless, after oral natural micronized P administration, P and 17alpha-hydroxyprogesterone (17-OHP) concentrations were increased, and HOMA-IR was decreased, whereas androgens levels were not altered, in comparison with baseline. CONCLUSION(S): The induction of withdrawal bleeding, with this regimen, does not appear to be a necessity for the assessment of hormonal and metabolic profile in anovulatory women with PCOS.

Hyperreninemia characterizing women with polycystic ovary syndrome improves after metformin therapy.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation, hyperandrogenemia and insulin resistance. Hyperreninemia is observed in insulin resistance and hyperandrogenemic states. AIMS: To investigate the levels of total plasma renin and their possible relationship with insulin resistance and hyperandrogenemia and to explore the effect of metformin on these parameters in PCOS women. METHODS: 48 PCOS women who were age- and body mass index (BMI)-matched with 21 healthy women were studied. Total renin, aldosterone levels, glucose and insulin levels were measured at basal state and during an oral glucose tolerance test in all subjects. A subgroup of women with PCOS was evaluated 6 months after metformin administration. RESULTS: Total renin levels were significantly higher in PCOS women compared to controls. PCOS women compared to controls displayed higher areas under the curve for glucose, insulin and total renin (AUCREN). Mean AUCREN was correlated significantly with insulin resistance indices and positively with free testosterone levels. Total renin, aldosterone, androgen levels and insulin sensitivity indices were significantly improved after 6 months on metformin treatment. CONCLUSIONS: PCOS women demonstrated an insulin resistance and hyperandogenemia-related increase in serum total renin levels. Metformin treatment was shown to significantly reduce total renin levels.

Postsynaptic N-methyl-D-aspartate receptor function requires alpha-neurexins.

Alpha-neurexins are neuron-specific cell-surface molecules that are essential for the functional organization of presynaptic Ca2+ channels and release sites. We have now examined postsynaptic glutamate receptor function in alpha-neurexin knockout (KO) mice by using whole-cell recordings in cultured neocortical slices. Unexpectedly, we find that alpha-neurexins are required for normal activity of N-methyl-D-aspartate (NMDA)- but not alpha-amino-3-hydroxy-5-methyl-4-isoxyzolepropionic acid (AMPA)-type glutamate receptors. In alpha-neurexin-deficient mice, the ratio of NMDA- to AMPA-receptor currents, recorded as evoked synaptic responses, was diminished approximately 50%. Furthermore, the NMDA-receptor-dependent component of spontaneous synaptic miniature responses was reduced approximately 50%, whereas the AMPA-receptor-dependent component was unaffected. No alterations in the levels of NMDA- or AMPA-receptor proteins were detected. These results suggest that alpha-neurexins are required to maintain normal postsynaptic NMDA-receptor function. The decrease in NMDA-receptor activity in alpha-neurexin-deficient synapses could be due to a transsynaptic effect on the postsynaptic neuron (i.e., alpha-neurexins on the presynaptic inputs guide postsynaptic NMDA-receptor function) or to a cell-autonomous postsynaptic effect of alpha-neurexins on NMDA-receptor activity. To distinguish between these two possibilities, we cocultured WT GFP-labeled neurons with neocortical slices from alpha-neurexin-deficient or control mice. No difference was found between WT neurons innervated by inputs that contained or lacked alpha-neurexins, indicating that the absence of presynaptic alpha-neurexins alone does not depress postsynaptic NMDA-receptor function. Our data suggest that, in addition to the previously described presynaptic impairments, loss of alpha-neurexins induces postsynaptic changes by a cell-autonomous mechanism.