Differentation of the fat body cells in the precocius adults of Schistocerca gregaria: regulation of polyploidy by juvenile hormone

Precocious adults from 2nd and 3rd instar larvae of the desert locust Schistocerca gregaria were used to assess the competence of their fat body to synthesize DNA in response to a juvenile hormone analog (JHA), hydoprene. Autoradiographic studies show that JHA stimulates DNA synthesis since a significant proportion of the fat body nuclei are labelled after treatment with 100 or 200 µg of JHA. Maximum DNA synthesis occurs 24 h after treatment with 100 µg of JHA. The nuclear ploidy classes of the precocious adults from 3rd larvae are similar to those of 1-d-old normal adults, but treatemnt of these precociuos adults with µg of JHA doubles the DNA content resulting in enhanced ploidy classes which resemble those of 10-d-old normal females. In the precocious adults that emerged from 2nd instar larvae the ploidy classes are higher than those of 1-d-old normal adults, and treatment of these precocious adults with JHA results in a further increase in the DNA content of the fat body nuclei leading to the formation of high percentages of 16C and 32C nuclei. The results of these studies suggest that any model on the mode of action of JH should recognize this phenomenon of JH-induced polyploidization in the fat body nuclei.

MC1R-dependent, melanin-based colour polymorphism is associated with cell-mediated response in the Eleonora's falcon.

Colour polymorphism in vertebrates is usually under genetic control and may be associated with variation in physiological traits. The melanocortin 1 receptor (Mc1r) has been involved repeatedly in melanin-based pigmentation but it was thought to have few other physiological effects. However, recent pharmacological studies suggest that MC1R could regulate the aspects of immunity. We investigated whether variation at Mc1r underpins plumage colouration in the Eleonora's falcon. We also examined whether nestlings of the different morphs differed in their inflammatory response induced by phytohemagglutinin (PHA). Variation in colouration was due to a deletion of four amino acids at the Mc1r gene. Cellular immune response was morph specific. In males, but not in females, dark nestling mounted a lower PHA response than pale ones. Although correlative, our results raise the neglected possibility that MC1R has pleiotropic effects, suggesting a potential role of immune capacity and pathogen pressure on the maintenance of colour polymorphism in this species.

Effect of precocene II, ecdysone and juvenile Hormone on the glicogen concentration in pupae of Stomocys calcitram (Diptera muscidae)

Third instar larvae of Stomoxys calcitrans (L.) were treated with precocene II, ecdysone and juvenile hormone. The larvae were allowed to develop until pupation and when it occurred, determination of glycogen levels was assayed. The administration of those three substances have interfered on the clycogen concentration. the precocene II causing a decrease whereas the ecdysone and juvenile hormone causing an increase. The ecdysone administered together withprecocene II reverses the effect of the latter. This does not happen when precocene II is administered together with the juvenile hormone. Ecdysone administered together with juvenilehormone causes reduction of the glycogen concentration.

Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor.

In this study, we describe a patient with a phenotype of complete hypogonadotropic hypogonadism who presented primary failure of pulsatile GnRH therapy, but responded to exogenous gonadotropin administration. This patient bore a novel point mutation (T for A) at codon 168 of the gene encoding the GnRH receptor (GnRH-R), resulting in a serine to arginine change in the fourth transmembrane domain of the receptor. This novel mutation was present in the homozygous state in the patient, whereas it was in the heterozygous state in both phenotypically normal parents. When introduced into the complementary DNA coding for the GnRH-R, this mutation resulted in the complete loss of the receptor-mediated signaling response to GnRH. In conclusion, we report the first mutation of the GnRH-R gene that can induce a total loss of function of this receptor and is associated with a phenotype of complete hypogonadotropic hypogonadism.

Juvenile hormone III and nutrition effects on spermatogenesis in the 4th instar nymphs of Panstrongylus megistus (Hemiptera: Reduviidae)

When 4th instar nymphs of Panstrongylus megistus are fed with a saturant blood meal, there is an intense proliferation of the spermatogonia. At the end of the intermoult, the older spermatogonial cysts differentiate into 1st primary spermatocyte cysts. In the nymphs deprived of the blood meal this evolution is not observed, but a small growth of the testicular follicles occurs, due to a few mitotic divisions. This growth is observed at least, until 25 days after ecdysis. Since day 15, an autolytic process starts in the older spermatogonial cysts. The presence of exogenous juvenile hormone III (JH III) does not promote the development of the germ cells in the fasting insects. There is only a small growth of the testicular follicles and the autolytic process is also observed. In the precocious adults obtained by allatectomy or precocene II treatment, germ cells are observed in all development stages, except packed and elongated spermatozoa bundels.

Feedback on hypothalamic TRH transcription is dependent on thyroid hormone receptor N terminus.

The beta thyroid hormone receptor (TRbeta), but not TRalpha1, plays a specific role in mediating T(3)-dependent repression of hypothalamic TRH transcription. To investigate the structural basis of isoform specificity, we compared the transcriptional regulation and DNA binding obtained with chimeric and N-terminally deleted TRs. Using in vivo transfection assays to follow hypothalamic TRH transcription in the mouse brain, we found that TRbeta1 and chimeras with the TRbeta1 N terminus did not affect either transcriptional activation or repression from the rat TRH promoter, whereas N-terminally deleted TRbeta1 impaired T(3)-dependent repression. TRalpha1 or chimeras with the TRalpha1 N terminus reduced T(3)-independent transcriptional activation and blocked T(3)-dependent repression of transcription. Full deletion of the TRalpha1 N terminus restored ligand-independent activation of transcription. No TR isoform specificity was seen after transcription from a positive thyroid hormone response element. Gel mobility assays showed that all TRs tested bound specifically to the main negative thyroid hormone response element in the TRH promoter (site 4). Addition of neither steroid receptor coactivator 1 nor nuclear extracts from the hypothalamic paraventricular nuclei revealed any TR isoform specificity in binding to site 4. Thus N-terminal sequences specify TR T(3)-dependent repression of TRH transcription but not DNA recognition, emphasizing as yet unknown neuron-specific contributions to protein-promoter interactions in vivo.

Impact du traitement par hormone de croissance sur la composition corporelle et le métabolisme osseux d'enfants nés avec un retard de croissance intra-utérin

Le retard de croissance intra-utérin (RCIU) est défini par une taille et un poids inférieurs au P10 pour l'âge gestationnel. Il est caractérisé, entre autre par une altération de la croissance foetale aboutissant à une résistance à l'hormone de croissance (HC). Bien que la majorité des sujets présente un certain rattrapage en taille, certains développent un retard de croissance ultérieur permanent. L'idée est donc née de traiter ces sujets par haute dose d'HC biosynthétique. La question des risques d'un tel traitement s'est posée en raison de l'effet diabétogène de l'HC et des modifications qu'elle peut induire sur la masse maigre, la masse grasse et la densité osseuse. Le but de l'étude a été d'évaluer l'impact sur la croissance et sur le volet métabolique. Dix enfants prépubères ayant présenté un RCIU sans croissance de rattrapage spontanée ont été traités par HC recombinante à des doses supra physiologiques (53-67 g/kg/jour). La taille, le poids, la taille assise ont été mesurés et des dosages d'IGF1, IGFBP3, glycémie et insuline ont été faits sur une base semestrielle alors qu'une densitométrie osseuse a été faite annuellement sur une période de 3 ans. Le gain en taille a été spectaculaire (+ 1.78 DS), correspondant à plus de 10 cm (p < 0.001). Sous traitement, l'insulinémie et le HOMA ont augmenté sans que ces augmentations soient significatives. La tolérance glucidique est restée dans la norme au prix d'une augmentation de la sécrétion d'insuline. La masse grasse a diminué alors que la masse maigre et la densité osseuse ont augmenté de façon significative. Ces résultats correspondent aux travaux d'autres groupes. Il reste à démontrer que l'hyperinsulinisme transitoire induit par l'HC n'ait pas d'effet néfaste à long terme et en particulier sur le risque de développer ou aggraver un syndrome métabolique à l'âge adulte.

Ectodysplasin regulates hormone-independent mammary ductal morphogenesis via NF-κB.

Ductal growth of the mammary gland occurs in two distinct stages. The first round of branching morphogenesis occurs during embryogenesis, and the second round commences at the onset of puberty. Currently, relatively little is known about the genetic networks that control the initial phases of ductal expansion, which, unlike pubertal development, proceeds independent of hormonal input in female mice. Here we identify NF-κB downstream of the TNF-like ligand ectodysplasin (Eda) as a unique regulator of embryonic and prepubertal ductal morphogenesis. Loss of Eda, or inhibition of NF-κB, led to smaller ductal trees with fewer branches. On the other hand, overexpression of Eda caused a dramatic NF-κB-dependent phenotype in both female and male mice characterized by precocious and highly increased ductal growth and branching that correlated with enhanced cell proliferation. We have identified several putative transcriptional target genes of Eda/NF-κB, including PTHrP, Wnt10a, and Wnt10b, as well as Egf family ligands amphiregulin and epigen. We developed a mammary bud culture system that allowed us to manipulate mammary development ex vivo and found that recombinant PTHrP, Wnt3A, and Egf family ligands stimulate embryonic branching morphogenesis, suggesting that these pathways may cooperatively mediate the effects of Eda.

Variation d'expression des récepteurs hormonaux et d'HER-2 dans l'évolution du cancer du sein : quelles implications en pratique clinique [Hormone receptors and HER-2 changes during breast cancer progression: clinical implications].

Breast cancer remains a major public health problem. Even if there is an increase in this cancer curability, metastatic breast cancer remains a lethal disease in the vast majority of cases. Therapeutic advances in the chemotherapeutic and targeted therapies fields induced an increase in survival, however the proportion of long survivors remains low. Phenotypic instability, an early process initiated during tumour progression, and continued on the metastatic stage of the disease, can be one of the putative hypotheses explaining these results. An increasing amount of scientific data are pledging for a reanalysis of the phenotypic profile regarding hormone receptors and HER-2 status of metastatic lesions in order to identify drugable targets and allow individualisation of the treatment of these metastatic breast cancer patients. Phenotypic changes between the primary tumour and the paired metastatic lymph nodes are a challenging pitfall, raising the question of which site has to be assessed in the adjuvant treatment decision process. This article presents a comprehensive analysis of the frequency of theses phenotypic changes altogether with new modalities to evaluate this phenotypic status.

Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injury.

Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine alpha-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission.

Melanin pigmentation negatively correlates with plumage preening effort in barn owls

1. According to the handicap principle of sexual selection, colourful ornaments honestly signal absolute quality only if they entail fitness costs. The degree of melanism often covaries positively with aspects of individual quality, and hence melanin-based coloration should be costly to produce or to maintain in a good shape. This is, however, unlikely because melanin-based coloration is often strongly heritable and in birds the rate of feather wear decreases with the amount of melanin pigments packed in feathers. 2. The hypothesis that melanin pigments reduce the cost of maintaining colourful ornaments in a good shape predicts a negative correlation between the degree of melanism and both the size of the uropygial gland that produces preening secretions and the intensity of preening behaviour. 3. Using a correlative approach, I evaluated these two predictions in the barn owl Tyto alba in which the body underside varies from immaculate to heavily marked with black spots, a eumelanin-based trait, and from white to reddish-brown, a phaeomelanin-based trait. I correlated plumage traits with preening behaviour in nestlings and with the size and mass of the uropygial gland in dead adults. I also weighed nonornamental wing and tail feathers to assess whether the quality of nonornamental feathers is positively correlated with the degree of melanism of an ornamental plumage trait. 4. The degree of phaeomelanism was neither associated with preening behaviour nor with the size and mass of the uropygial gland. In line with the two predictions, individuals with more and larger black spots had a lighter uropygial gland and preened less frequently. Because nonornamental wing and tail feathers of spottier individuals were heavier per unit of surface area, the entire plumage of eumelanic individuals may be more robust and in turn require less care than the plumage of nonmelanic conspecifics. 5. In conclusion, the degree of eumelanism can be associated with aspects of individual quality even if eumelanic ornaments are neither costly to produce nor to maintain in a good shape. Document Type: Article

Acute creatine loading enhances human growth hormone secretion.

BACKGROUND: The main objective of this study was to explore the effect of acute creatine (Cr) ingestion on the secretion of human growth hormone (GH). METHODS: In a comparative cross-sectional study, 6 healthy male subjects ingested in resting conditions a single dose of 20 g creatine (Cr-test) vs a control (c-test). During 6 hours the Cr, creatinine and GH concentrations in blood serum were measured after Cr ingestion (Cr-test). RESULTS: During the Cr-test, all subjects showed a significant stimulation of GH (p<0.05), but with a large interindividual variability in the GH response: the difference between Cr-test and c-test averaged 83% (SD 45%). For the majority of subjects the maximum GH concentration occurred between 2 hrs and 6 hrs after the acute Cr ingestion. CONCLUSIONS: In resting conditions and at high dosages Cr enhances GH secretion, mimicking the response of strong exercise which also stimulates GH secretion. Acute body weight gain and strength increase observed after Cr supplementation should consider the indirect anabolic property of Cr.

Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.

BACKGROUND: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. METHODS: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). RESULTS: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. CONCLUSION: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.