Publications of Marie-Christine LEBRETHON
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See detailA series of 9 pregnancies with hyperthyroidism and Graves disease : fetal and maternal follow up
DELANNOY, Pauline ULiege; GRANDFILS, Sébastien ULiege; LEBRETHON, Marie-Christine ULiege et al

in Abstract book : Annual congress of the Belgian Society of Internal Medicine (2019, December)

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See detailPoor growth response during the first year of growth hormone treatment in short prepubertal children with growth hormone deficiency and born small for gestational age: a comparison of different criteria.
Straetemans, Saartje; Thomas, Muriel; Craen, Margarita et al

in International Journal of Pediatric Endocrinology (2018), 2018

Background: There is no consensus on the definition of poor growth response after the first year of growth hormone (GH) treatment. We determined the proportion of poor responders identified by different ... [more ▼]

Background: There is no consensus on the definition of poor growth response after the first year of growth hormone (GH) treatment. We determined the proportion of poor responders identified by different criteria in children with GH deficiency (GHD) and born small for gestational age (SGA). The second aim was to analyze the IGF-1 response in poor growth responders. Methods: First-year height data of 171 SGA and 122 GHD children who remained prepubertal during the first GH treatment year were retrieved from the BESPEED database and analyzed. Criteria for poor first-year response/responsiveness were: change in height (Ht) SDS<0.3 or<0.5, height velocity (HV) SDS<0.5 or <1 based on the population reference, HV SDS<- 1 based on the KIGS expected HV curve (HV Ranke SDS), studentized residual (SR) <- 1 in the KIGS first-year prediction model. Results: Ht SDS<0.5 gave the highest percentage poor responders (37% SGA, 26% GHD). Although % poor responders were comparable for Ht SDS<0.3, HV SDS<+ 0.5, HV SDS<+ 1, SR<- 1, and HV Ranke SDS<- 1, these criteria did not always identify the same patients as poor responders. Among the poor growth responders 24% SGA and 14% GHD patients had an IGF-1 increase < 40%. Conclusions: The different response criteria yield high but comparable percentages poor responders, but identify different patients. This study does not provide evidence that one criterion is better than another. A limited IGF-1 generation is not the major reason for a poor growth response in the first year of GH treatment in SGA and GHD children. Trial registration: Retrospectively registered. [less ▲]

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See detailAdult Height after Growth Hormone Treatment at Pubertal Onset in Short Adolescents Born Small for Gestational Age: Results from a Belgian Registry-Based Study.
Thomas, M.; Beckers, D.; Brachet, C. et al

in International Journal of Endocrinology (2018), 2018

Objectives: Information on the efficacy of GH treatment in short SGA children starting their treatment in adolescence is limited. Therefore, adult height (AH), total height gain, and pubertal height gain ... [more ▼]

Objectives: Information on the efficacy of GH treatment in short SGA children starting their treatment in adolescence is limited. Therefore, adult height (AH), total height gain, and pubertal height gain were evaluated in short SGA children who started GH treatment at pubertal onset. Patient and Methods: Growth data of 47 short SGA adolescents (22 boys) who started GH treatment at pubertal onset (PUB group) were compared with results from 27 short SGA patients (11 boys) who started GH therapy at least 1 year before pubertal onset (PrePUB group). Results: The PUB group achieved a mean (+/-SD) total height gain of 0.8 +/- 0.7 SDS and an AH of -2.5 +/- 0.7 SDS after 4.1 +/- 1.1 years of GH treatment with a dosage of 41.8 +/- 8.4 mug/kg/day. These results were comparable with those in the PrePUB group, which was treated for a longer duration (5.8 +/- 2.1 years), resulting in a total height gain of 1.1 +/- 0.7 SDS and an AH of -2.1 +/- 1.0 SDS. Multiple regression analysis showed a significantly lower height gain in pubertal patients, females, and patients weighing less at start of GH treatment. An AH above -2 SDS and above the parent-specific lower limit of height was, respectively, reached in 28% and 70% of PUB and 44% and 67% of PrePUB patients (NS). AH SDS was positively correlated with the height SDS at start of GH. Conclusions: Short SGA adolescents starting GH therapy at an early pubertal stage have a modest and variable height gain. A normal AH can be expected in one third of the patients, especially in those with a smaller height deficit at onset of GH treatment. [less ▲]

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See detailLow/medium doses of inhaled corticosteroids can cause adrenal insufficiency
FUDVOYE, Julie ULiege; LEBRETHON, Marie-Christine ULiege; Parent, Anne-Simone ULiege

in Belgian Journal of Paediatrics (2017, March), 19(1),

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See detailEtude rétrospective du bilan thyroïdien: définition de valeurs de référence pédiatriques
LADANG, Aurélie ULiege; VRANKEN, Laura ULiege; LUYCKX, Françoise ULiege et al

in Revue Médicale de Liège (2017)

Defining reference range is an essential tool for diagnostic. Age and sexe influences on thyroid hormone levels have been already discussed. In this study, we are defining a new pediatric reference range ... [more ▼]

Defining reference range is an essential tool for diagnostic. Age and sexe influences on thyroid hormone levels have been already discussed. In this study, we are defining a new pediatric reference range for TSH, FT3 and FT4 for Cobas C6000 analyzer. To do so, we have taken in account 0 to 18 year old outclinic patients. During the first year of life, thyroid hormone levels change dramatically before getting stabilized around 3 years old. We also compared our results to those obtained in a Canadian large-scale prospective study (the CALIPER initiative). [less ▲]

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See detailDesign and implementation of a ‘physical activity day’ for overweight and obese youth
Cloes, Marc ULiege; DEWANDRE, Anne-Cécile ULiege; LEBRETHON, Marie-Christine ULiege et al

Conference (2015, March)

This study aimed to analyze the development and implementation of an adapted physical activity day expected to underline to overweight/obese youth the role of PA and hw they could be more active in their ... [more ▼]

This study aimed to analyze the development and implementation of an adapted physical activity day expected to underline to overweight/obese youth the role of PA and hw they could be more active in their daily life. [less ▲]

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See detailDevelopment of educational info capsules proposing instructional strategies aiming to deal with overweight and obese students
Cloes, Marc ULiege; LEBRETHON, Marie-Christine ULiege; Feron, Isaline

Conference (2014, February 13)

Irwin et al. (2003) pointed out the principles that quality PE teachers should incorporate into their pedagogical practice in order to take into account the increasing number of overweight and obese ... [more ▼]

Irwin et al. (2003) pointed out the principles that quality PE teachers should incorporate into their pedagogical practice in order to take into account the increasing number of overweight and obese students in their classes. Fighting against obesity is so complex that no simple solution can be proposed. It means that the development of specific tools providing PE teachers with new instructional strategies inspired from public health is needed (Prusak et al., 2011). Inclusion of overweight students into PE can be linked with a social ecological model (Li & Rukavina, 2012). Even if PE teachers are able to develop and implement specific instructional strategies, it seems that they need support from health experts (Cloes et al., 2013). Internet, continuing professional development activities, and educational info capsules were identified as the preferred supports to be used by the practitioners (Cloes et al., 2014). The aims of this study were to produce and validate three pedagogical capsules focusing on specific concerns of PE teachers as well as to analyze the procedure of validation. Using an extensive analysis of the literature, the researchers first identified theoretical and practical resources to be mobilized in the understanding and development of solutions for the selected problems: (1) Students’ lack of awareness about the risks of overweight and obesity; (2) Constraints associated with the motor/physical disabling; (3) Parents’ lack of awareness about PA impact on health. The capsules were then submitted to 11 experts (health specialists, health educators, psychologists, PE teachers) who had to analyze the documents. They acknowledged the content and form of the capsules. Minor changes were requested in order to finalize them. The proposed evaluation sheet was also validated but face-to-face assessment was recommended. Dissemination of the existing capsules as well as development of additional ones should be the next steps of this project. [less ▲]

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See detailConstraints experienced by physical education teachers with overweight and obese students
Cloes, Marc ULiege; Feron, Isaline; LEBRETHON, Marie-Christine ULiege

Conference (2014, February 10)

Despite ‘antifat’ attitude of some PE teachers (Greenleaf & Weiller, 2005) and the PE public relations problem in regard to how obese students are treated (Irwin et al., 2003), it seems evident that this ... [more ▼]

Despite ‘antifat’ attitude of some PE teachers (Greenleaf & Weiller, 2005) and the PE public relations problem in regard to how obese students are treated (Irwin et al., 2003), it seems evident that this school subject represents a key element in the involvement of the education sector in the fight against the worldwide escalating global epidemic of obesity (Tappe & Burgeson, 2004). In fact, PE teachers consider that they lack of specific knowledge to implement instructional strategies dealing with overweight and obese students (Cloes & Ziant, 2009). Some authors proposed models to illustrate constraints that PE teachers encounter in their classes with obese students and their potential solutions (Cloes et al., 2013; Rukavina et al., 2010). On the other hand, data are missing when identifying those that are considered as their main concerns and the ways that they would prefer to receive some support regarding this specific topic. This study is focused on these two aspects. Five hundred thirteen PE teachers fulfilled an online questionnaire (Lickert scales) in which they had to determine (1) the perceived importance of 20 problems proposed by PE teachers and validated by 8 experts; (2) their relative interest toward the reception of support aiming to deal with those problems; (3) their preference for receiving information about the potential instructional strategies. Based on the answers, the top 3 problems are: (1) Students’ lack of awareness about the risks of overweight and obesity; (2) Constraints associated with the motor/physical disabling; (3) Parents’ lack of awareness about physical activity impact on health. Internet (3.49±.6/4), continuing professional development activities (3.29±.8/4), and educational info capsules (3.07±.8/4) were identified as the main resources that PE teachers would use preferentially. This study provides useful information for PE teachers’ educators who should develop now material to be shared with the practitioners. [less ▲]

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See detailL'hyperthyroidie neonatale: clinique et prise en charge therapeutique.
Petignot, S.; NYAMUGABO MUNYERE NKANA, Kindja ULiege; Socin, H. Valdes et al

in Revue Médicale de Liège (2013), 68(10), 531-6

Neonatal hyperthyroidism is a rare pathology, most often the consequence of Graves' disease in the mother. Around 0.2% of pregnant women have Graves disease and 1 to 2% of newborns of mother with Graves ... [more ▼]

Neonatal hyperthyroidism is a rare pathology, most often the consequence of Graves' disease in the mother. Around 0.2% of pregnant women have Graves disease and 1 to 2% of newborns of mother with Graves' disease. This article will describe the case of 4 newborns who have been diagnosed and treated in CHU-NDB between 2007 and 2011. The second part will focus on the new recommendations about the management of these young patients from foetal period to birth. [less ▲]

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See detailWhat is proposed to overweight and obese youth in a sample of fitness centres?
Cloes, Marc ULiege; LEBRETHON, Marie-Christine ULiege; Fortemps, Grégory

Poster (2013, May)

Purpose. Overweight and obesity take a growing place in the public health preoccupations as the proportion of people over the normal BMI limit increases dramatically year after year. This evolution could ... [more ▼]

Purpose. Overweight and obesity take a growing place in the public health preoccupations as the proportion of people over the normal BMI limit increases dramatically year after year. This evolution could have devastating consequences on the economy for years and possibly generations to come. Youth physical activity is pointed out as a priority. Fitness centres are possible partners of health services. This study aimed to know if overweight/obese youth could be welcomed into a sample of fitness centres. Methods. A sample of 13 fitness centres of the Liege area was visited. Fourteen interviews with the managers have been conducted. Specific questions were asked about what is proposed to overweight and obese people and specifically to youth group. Content analysis has been done from verbatim transcripts. Results. Most of the subjects consider that overweight/obese youth could encounter some difficulties to adhere to a fitness centre. Unfounded embarrassment about the look of others is underlined by 7 out of the managers. The real intrinsic motivation of the youth would be a key factor as well as real difficulties to use the equipment. Few fitness centres currently propose specific activities but 7 would be ready to collaborate with a medical unit in order to propose specific activities. Two decided to stop such initiatives according to the cost and lack of perseverance of the youth. Conclusions. This study showed that fitness centres managers would be interested to implement initiatives to offer specific services to overweight/obese youth but it would require collaboration with health services. [less ▲]

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See detailPhysical Activity Promotion In Overweight/Obese Children. A Project Implemented In A Hospital Context
Cloes, Marc ULiege; DEWANDRE, Anne-Cécile ULiege; LEBRETHON, Marie-Christine ULiege

Conference (2012)

BACKGROUND. Overweight and obesity in youth must be combated through a multiple approach combining management principles in nutrition and physical activity (PA). In the hospital context, medical staff ... [more ▼]

BACKGROUND. Overweight and obesity in youth must be combated through a multiple approach combining management principles in nutrition and physical activity (PA). In the hospital context, medical staff seems to be more focused on nutrition. AIM. In this study, we proposed to implement a specific intervention focusing on PA in parallel with traditional paediatric and dietetic visits designed to 6-12 year-old children. METHODS. Data were collected in three steps: (1) after a visit at the hospital, subjects and their parents answered to a questionnaire (lifestyle, representation about PA) and attended to a meeting during which they received written (illustrated booklet) and oral cues about PA as well as an invitation to use a PA diary and a pedometer; (2) before the next visit (almost 8 weeks interval), they were free to apply the recommendations; (3) after the next visit to the hospital, subjects analyzed the diary with one of the researchers and answered to questions about their current lifestyle and representations about PA. 34 children respected the whole protocol. FINDINGS. Among the children and their parents, representations of PA changed between the visits (PA was no longer regarded merely as sport). Major changes were also identified in children’s lifestyle (increase of number of weekly PA, family PA, weekly PA time; decrease of inactivity time like TV or video games). Only 27 children out of 34 used the PA diary at least once (information were recorded for a mean of 18 days/child between the 2 visits – a third of the duration of the interval). The pedometer has been used by 15 children and was considered as a motivating tool. 58.5% of comments collected at the end of the second meeting were positive and emphasized the interest of the intervention; 24.6% were negative and mainly focused the PA diary). DISCUSSION. This study underlines the need to improve the family's representations about PA in paediatric and dietetic visits. It supports PA experts' integration in the staff. [less ▲]

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See detailComment j'explore les hypoglycémies chez l'enfant : à propos de deux cas
HARVENGT, Julie ULiege; DEBRAY, François-Guillaume ULiege; LEBRETHON, Marie-Christine ULiege et al

in Revue Médicale de Liège (2011), 66(12), 631-635

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See detailDe l'utilité d'une consultation conjointe de gynécologie- endocrinologie pédiatrique : étude rétrospective des motifs de consultation et approche pratique
HARVENGT, Julie ULiege; Retz, M.-C.; Foidart, Jean-Michel ULiege et al

in Revue Médicale de Liège (2011), 66(11), 581-8

The gynaecological issues encountered in children and teenagers lay at the intersection of paediatric endocrinology and gynaecology. More than ten years ago, an outpatient clinic in paediatric ... [more ▼]

The gynaecological issues encountered in children and teenagers lay at the intersection of paediatric endocrinology and gynaecology. More than ten years ago, an outpatient clinic in paediatric endocrinology and gynaecology has been created. Here, we review the last 6 years. 214 girls were included, considering only the first visit for each patient. Collected data are initial concern for this consultation, age at first consultation and confirmed or suspected diagnosis. A classification is done according to the initial concern of patients in six categories. Principal queries concern pubertal development, precocious pilosity or abnormalities in menstrual cycles. Vulvovaginitis and morphologic abnormalities are also frequently encountered. This consultation suggests a paediatric approach with a child feeling confident and a gynaecological examination with a specialist knowing the anatomy particularities and the development of the children. This article focuses on the importance of specific gynaecological examination in children and reviews the main diseases encountered. [less ▲]

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See detailManagement of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization.
Descamps, O. S.; Tenoutasse, S.; Stephenne, X. et al

in Atherosclerosis (2011), 218(2), 272-80

Since heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a ... [more ▼]

Since heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations. Conclusion: The aim of this consensus statement is to achieve more consistent management in the identification and treatment of children with HeFH in Belgium. [less ▲]

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See detailNeuroendocrine disruption of pubertal timing and interactions between homeostasis
Bourguignon, Jean-Pierre ULiege; Rasier, Gregory ULiege; Lebrethon, Marie-Christine ULiege et al

in Molecular and Cellular Endocrinology (2010), 324(1-2), 110-120

The involvement of environmental factors such as endocrine disrupting chemicals (EDCs) in the timing of onset of puberty is suggested by recent changes in age at onset of puberty and pattern of ... [more ▼]

The involvement of environmental factors such as endocrine disrupting chemicals (EDCs) in the timing of onset of puberty is suggested by recent changes in age at onset of puberty and pattern of distribution that are variable among countries, as well as new forms of sexual precocity after migration. However, the evidence of association between early or late pubertal timing and exposure to EDCs is weak in humans, possibly due to heterogeneity of effects likely involving mixtures and incapacity to assess fetal or neonatal exposure retrospectively. The neuroendocrine system which is crucial for physiological onset of puberty is targeted by EDCs. These compounds also act directly in the gonads and peripheral sex-steroid sensitive tissues. Feedbacks add to the complexity of regulation so that changes in pubertal timing caused by EDCs can involve both central and peripheral mechanisms. In experimental conditions, several neuroendocrine endpoints are affected by EDCs though only few studies including from our laboratory aimed at EDC involvement in the pathophysiology of early sexual maturation. Recent observations support the concept that EDC cause disturbed energy balance and account for the obesity epidemic. Several aspects are linking this system and the reproductive axis: coexisting neuroendocrine and peripheral effects, dependency on fetal/neonatal programming and the many factors cross-linking the two systems, for instance leptin, adiponectin, Agouti Related Peptide (AgRP). This opens perspectives for future research and, hopefully, measures preventing the disturbances of homeostasis caused by EDCs. [less ▲]

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See detailComment j'EXPLORE ... un hypogonadisme hypogonadotrope congenital isole
VALDES SOCIN, Hernan Gonzalo ULiege; Debray, François-Guillaume ULiege; Parent, Anne-Simone ULiege et al

in Revue Médicale de Liège (2010), 65(11), 634-41

Congenital Isolated hypogonadotropic hypogonadism (CIHH) is caused by an inherited mechanism of impairment of the pituitary-gonadal axis, interfering with gonads' control. Currently, different forms of ... [more ▼]

Congenital Isolated hypogonadotropic hypogonadism (CIHH) is caused by an inherited mechanism of impairment of the pituitary-gonadal axis, interfering with gonads' control. Currently, different forms of HHCI with (Kallmann syndrome or KS) or without anosmia-hyposmia are known. There are six forms of KS already described but in several cases no genetic mutation is found. The genetic anomalies already described are: KAL1 (locus Xp23) coding for anosmine-1, KAL-2 or FGFRI (8p11. locus 2 - p11.1) coding for Fibroblast Growth Factor Receptor 1 (FGFR1), KAL4 or PROk2 (locus 3p21.1) and KAL3 or ProKR2 (locus 20p13) coding respectively for the Prokinecitin-2 and its receptor, KAL5 or CHD7 (locus_8q12.1) coding for a chromodomain helicase DNA-binding protein-7 gene (CHD7) and lastly KAL6 or FGF8 (10Q 24 loci) coding for Fibroblast Growth Factor 8. The other genetic anomalies without anosmia are less frequent. These are associated either with Gnrhl gene (8p2-11. 2), GnRHR (4q21.2), GPR54 (19p13),TAC3R or neurokinine receptor 3 (4 q 25), LH (19q13.32) or FSH (11p13). The isolated congenital hypogonadotrophic hypogonadism phenotype is variable depending on gender, the importance of the deficit, and ultimately, according to a specific regulatory mechanism of the axis, affected by an inherited genetic anomaly. In this review, we describe the essential aspects of the different phenotypes and genotypes of HHCI, in order to assess clinicians an early disease's diagnosis and management. [less ▲]

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See detailAdult final height after GH therapy for irradiation-induced GH deficiency in childhood survivors of brain tumors: the Belgian experience.
Beckers, D.; THOMAS, M.; Jamart, J. et al

in European Journal of Endocrinology (2010), 162(3), 483-90

OBJECTIVES: The treatment of brain tumors in childhood is frequently complicated by growth retardation with a high proportion of irradiation (Irr)-induced GH deficiency (GHD) resulting in reduced adult ... [more ▼]

OBJECTIVES: The treatment of brain tumors in childhood is frequently complicated by growth retardation with a high proportion of irradiation (Irr)-induced GH deficiency (GHD) resulting in reduced adult final height (AFH) even after GH therapy (GHT). In order to optimize future GHT protocols, more information on the factors influencing the growth response to GH in these children is needed. This retrospective study evaluated AFH and influencing auxological and treatment factors of a standardized daily biosynthetic GHT in childhood survivors of brain tumors with documented GHD after brain Irr. DESIGN AND METHODS: From the Belgian GH Registry, 57 children survivors of a brain tumor outside the hypothalamo-pituitary area with available AFH were stratified into two groups depending on cranial (C-Irr; n=25) or craniospinal (CS-Irr; n=32) Irr. RESULTS: In the C-Irr patients, results showed an AFH of -0.8 (-2.5, 1.4) SDS (median (range)) and in the CS-Irr patients, results showed a significantly (P<0.001) lower AFH of -1.8 (-4.2, 0.0) SDS. AFH SDS corrected for mid-parental height (MPH) in the C-Irr group was -0.5 (-2.2, 0.9) and -1.5 (-3.6, 0.0) SDS in the CS-Irr group. AFH was positively correlated with age at end of tumor therapy, height SDS at start GHT, height gain SDS first year GHT, and negatively correlated with CS-Irr. CONCLUSIONS: GHT failed to restore adult height to MPH in nearly half of Irr-induced GHD patients for brain tumor, especially those receiving CS-Irr, irradiated at a younger age or shorter at start GHT. [less ▲]

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See detailMechanisms of Interaction of Endocrine-Disrupting Chemicals with Glutamate-Evoked Secretion of Gonadotropin-Releasing Hormone
Rasier, Gregory ULiege; Parent, Anne-Simone ULiege; Gerard, Arlette ULiege et al

in Toxicological Sciences (2008), 102(1), 33-41

In previous studies, we detected a dichlorodiphenyltrichloroethane (DDT) derivative in the serum of children with sexual precocity after migration from developing countries. Recently, we reported that DDT ... [more ▼]

In previous studies, we detected a dichlorodiphenyltrichloroethane (DDT) derivative in the serum of children with sexual precocity after migration from developing countries. Recently, we reported that DDT stimulated pulsatile gonadotropin-releasing hormone (GnRH) secretion and sexual maturation in the female rat. The aim of this study was to delineate the mechanisms of interaction of endocrine-disrupting chemicals including DDT with GnRH secretion evoked by glutamate in vitro. Using hypothalamic explants obtained from 15-day-old female rats, estradiol (E2) and DDT caused a concentration-related increase in glutamate-evoked GnRH release while p,p'-dichlorodiphenyldichloroethene and methoxychlor had no effect. The effective DDT concentrations in vitro were consistent with the serum concentrations measured in vivo 5 days after exposure of immature rats to 10 mg/kg/day of o,p'-DDT. Bisphenol A induced some stimulatory effect, whereas no change was observed with 4-nonylphenol. The o,p'-DDT effects in vitro were prevented partially by a selective antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptors. A complete prevention of o,p'-DDT effects was caused by an estrogen receptor (ER) antagonist as well as an aryl hydrocarbon receptor (AHR) antagonist and inhibitors of protein kinases A and C and mitogen-activated kinases. While an intermittent incubation with E2 caused no change in amplification of the glutamate-evoked GnRH release for 4 h, continuous incubation with E2 or o,p'-DDT caused an increase of this amplification after 3.5 h of incubation. In summary, DDT amplifies the glutamate-evoked GnRH secretion in vitro through rapid and slow effects involving ER, AHR, and AMPA receptor mediation. [less ▲]

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See detailOxytocin Facilitates Female Sexual Maturation through a Glia-to-Neuron Signaling Pathway
Parent, Anne-Simone ULiege; Rasier, Grégory ULiege; Matagne, V. et al

in Endocrinology (2008), 149(3), 1358-65

It has been earlier proposed that oxytocin could play a facilitatory role in the preovulatory LH surge in both rats and humans. We here provide evidence that oxytocin also facilitates sexual maturation in ... [more ▼]

It has been earlier proposed that oxytocin could play a facilitatory role in the preovulatory LH surge in both rats and humans. We here provide evidence that oxytocin also facilitates sexual maturation in female rats. The administration of an oxytocin antagonist for 6 d to immature female rats decreased GnRH pulse frequency ex vivo and delayed the age at vaginal opening and first estrus. The in vitro reduction in GnRH pulse frequency required chronic blockade of oxytocin receptors, because it was not acutely observed after a single injection of the antagonist. Hypothalamic explants exposed to the antagonist in vitro showed a reduced GnRH pulse frequency and failed to respond to oxytocin with GnRH release. Prostaglandin E(2) (PGE(2)) mimicked the stimulatory effect of oxytocin on GnRH pulse frequency, and inhibition of PG synthesis blocked the effect of oxytocin, suggesting that oxytocin accelerates pulsatile GnRH release via PGE(2). The source of PGE(2) appears to be astrocytes, because oxytocin stimulates PGE(2) release from cultured hypothalamic astrocytes. Moreover, astrocytes express oxytocin receptors, whereas GnRH neurons do not. These results suggest that oxytocin facilitates female sexual development and that this effect is mediated by a mechanism involving glial production of PGE(2). [less ▲]

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