The impact of intellectual disability and sport expertise on cognitive and executive functions.

Our aim was to identify the suitability of three assessment tools (i.e., Flanker test, Updating Word Span, and Color Trails Test) for future inclusion in the classification process of elite Paralympic athletes with intellectual disability and to assess the strength of the relation between Executive function (EF) and intelligence. Cognitive and EF assessments were performed on 59 participants, divided into four groups according to their cognitive level (with versus without intellectual disability) and sport expertise (athlete versus novice). Inhibition and working memory update skills were implicated in people with intellectual disability. For set-shifting, a more nuanced picture was observed. Strong associations between EF and intelligence was found in people with intellectual disability. Working memory updating and set-shifting are relevant EF skills to assess in the context of elite sport; however, culture-free alternatives for the Updating Word Span test are needed, and alternatives to the Color Trails Test, less reliant on literacy skills are required.

Validation of the Spanish Version of the Food Allergy Quality of Life Questionnaire-Parent Form (S-FAQLQ-PF).

BACKGROUND: Food allergy is an emerging health problem. Several questionnaires can be used to establish health-related quality of life (HRQOL) in food allergy patients. Current questionnaires should be translated in such a way that they take account of the culture of the country in which they are to be used. Objective: To translate and perform a cross-sectional validation of the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF). METHODS: The parents of 54 children diagnosed with food allergy were recruited to assess the Spanish version of the FAQLQ-PF (S-FQLQ-PF). RESULTS: The S-FQLQ-PF was translated into Spanish according to WHO guidelines (including a forward-backward translation). The statistical analysis showed that feasibility, reliability, and internal consistency were very good for the global S-FAQLQ-PF score and for the different domains. Assessment of construct validity indicated that S-FAQLQ-PF has reduced capacity for measurement of HRQOL in younger children. Cross-sectional validation of the S-FAQLQ-PF demonstrated that HRQOL of a Spanish pediatric population was affected by patient age, severity of symptoms, and number of reactions. HRQOL was not affected by sex, food implicated, number of foods implicated, ingestion of the implicated food, or presence of anaphylaxis. CONCLUSIONS: Translation into Spanish and cultural validation of the FAQLQ-PF demonstrated the influence of factors, such as patient age, severity of symptoms, and number of reactions on the HRQOL of a pediatric Spanish population.

Infant and Parent Outcomes Related to NICU-Based Co-occupational Engagement.

Neonatal intensive care unit (NICU) co-occupations may impact parent-infant outcomes. The main objective of this study was to explore relationships between parent and infant outcomes based on whether sensory-based interventions (co-occupations) occurred most often between parent-infant dyads or provider/volunteer-infant dyads. Thirty-five families received the Supporting and Enhancing NICU Sensory Experiences (SENSE) program, which includes education defining specific amounts of sensory exposures for infants to receive each day of NICU hospitalization (with a preference for parent delivery). Infant sensory experiences in the NICU were logged, and dyads were grouped based on who conducted most of the sensory interventions with the infant in the NICU into a Parent-Infant Co-occupation group or Other Administered group. The Parent-Infant Co-occupation group had infants with less lethargy on the NICU Network Neurobehavioral Scale (p = .04), and parents with lower scores on the Parental Stress Scale (p = .003) and State-Trait Anxiety Inventory-state (p = .047). Parent-infant engagement in co-occupations was related to parental mental health and infant neurobehavior.

Skin test-positive immediate hypersensitivity reaction to iodinated contrast media: the role of controlled challenge testing.

BACKGROUND: Immediate hypersensitivity reactions (IHR) to iodinated contrast media (ICM) have traditionally been considered nonallergic; however, the increasingly frequent reporting of positive skin test and basophil activation test results suggests a specific allergic mechanism in some patients. Skin tests have been proposed as a useful tool for diagnosis, although their sensitivity and predictive values remain to be determined. The role of controlled challenge testing has not been assessed. OBJECTIVE: We aimed to evaluate the role of controlled challenge testing in skin test-positive IHR to ICM. PATIENTS AND METHODS: We evaluated 106 patients with IHR to ICM by performing skin tests with the agent that caused the reaction. Patients with a positive result were selected. Skin tests were extended to a series of 8 ICMs; 5 patients underwent controlled challenge test with an alternative skin test-negative ICM; a further 2 patients underwent computed tomography with an alternative skin test-negative ICM. No premedication was administered. RESULTS: Intradermal test results were positive to the ICM that caused the reaction in 11 out of 106 patients (10.4%). Five of the 11 patients tolerated a controlled challenge test with an alternative skin test-negative ICM. The 2 patients who underwent computed tomography with an alternative skin test-negative ICM tolerated the medium. CONCLUSIONS: Skin tests are useful for the diagnostic workup in patients with an allergic IHR to ICM. Since ICM cannot be avoided in many patients because they are irreplaceable in some diagnostic or therapeutic techniques, an alternative safe ICM should be investigated for future procedures. We propose the use of controlled challenge tests based on skin test results to address this need in skin test-positive reactions in order to identify an alternative non-cross-reactive ICM.

Factors associated with feeding difficulties in the very preterm infant.

AIM: To investigate early medical and family factors associated with later feeding risk in preterm infants. METHODS: For this longitudinal study, 136 infants born ≤30 weeks gestation were enrolled. Medical and social background factors were assessed at term equivalent age. Infants underwent magnetic resonance imaging, neurobehavioral evaluation and feeding assessment. Parent involvement in the neonatal intensive care unit was tracked, and maternal mental health was assessed at neonatal intensive care unit discharge. At age 2 years, feeding outcome was assessed using the Eating Subscale of the Infant-Toddler Social Emotional Assessment (n = 80). Associations between feeding problems at age 2 years and (i) early medical factors, (ii) neurobehavioral functioning and feeding at term equivalent age, (iii) cerebral structure and (iv) maternal mental health were investigated using regression. RESULTS: Eighteen (23%) children had feeding problems at age 2 years. Feeding problems were associated with early hypotonia (p = 0.03; ß = 0.29) and lower socio-economic status (p = 0.046; ß = -0.22). No associations were observed between early medical factors, early feeding performance, cerebral structure alterations or maternal well-being and feeding outcome. CONCLUSION: Early hypotonia may disrupt the development of oral-motor skills. Hypotonia and poor feeding also may share a common aetiology. Associations with lower socio-economic status highlight the potential influence of family background factors in feeding problems in the preterm infant.

Parent-infant interaction in the NICU: Challenges in measurement.

BACKGROUND: Parent-infant interaction is poorly understood among high-risk dyads in NICU settings. No parent-infant interaction measures are specifically designed for preterm infants within the NICU nor account for the education NICU parents receive to tailor their interactions based on the infant's cues. AIM: To improve our understanding of a measure of parent-infant interaction in the NICU, we investigated relationships between parent-infant interaction scores on the Nursing Child Assessment Feeding Scale (NCAFS) and 1) socio-demographic and medical factors, 2) parent mental health and confidence, and 3) enhanced parental education (delivered as part of the Supporting and Enhancing NICU Sensory Experiences program) on tailoring interactions based on the infant's cues. METHOD: Twenty-six preterm infants (born ≤32 weeks) had a video recorded oral feeding conducted by a parent in the NICU when the infant was 34-48 weeks postmenstrual age. A certified evaluator scored parent-infant interaction from the videos using the NCAFS. RESULTS: Seventeen (65 %) parent-infant dyads scored below the 10th percentile on the total NCAFS score. Despite it being well-understood that parent-infant interaction is related to sociodemographic factors and parental mental health, there were no relationships between these factors and NCAFS scores in this study. Dyads who received enhanced parent education (n = 15) had lower NCAFS scores than dyads receiving usual care (n = 11) (p = 0.01). CONCLUSION: It remains unclear if the standard measure of parent-infant interaction, NCAFS, captured positive and negative interactions in context of assessment of a high-risk dyad within the NICU setting. The utility of the NCAFS with preterm infants in the NICU was not supported by this study.

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects.

Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function, was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation.

Characterization of the inhibitory roles of RFRP3, the mammalian ortholog of GnIH, in the control of gonadotropin secretion in the rat: in vivo and in vitro studies.

RF-amide related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone (GnIH), have been proposed as key regulators of gonadotropin secretion in higher vertebrates. Yet considerable debate has arisen recently on their physiological relevance and potential mechanisms and sites of action. Present studies were undertaken to further characterize the effects of RFRP on LH and FSH secretion by a combination of in vivo and in vitro approaches in male and female rats. Initial screening via intracerebroventricular (icv) administration of different analogs of RFRP1 (RFRP1-12 and RFRP1-20) and RFRP3 (RFRP3-8 and RFRP3-17), as well as the related neuropeptide FF (NPFF8), to gonadectomized (GNX) female rats evidenced significant, albeit modest, inhibitory effects on LH secretion only for RFRP3-8 and RFRP3-17, which were detectable at the high dose rage (1 nmol for RFRP3-8, 5 nmol for RFRP3-17). This moderate inhibitory action was also documented after icv administration of RFRP3-8 to intact and GNX male rats. In addition, systemic (intravenous) administration of RFRP3-8 decreased the circulating levels of both gonadotropins in GNX male rats. Likewise, RFRP3-8 inhibited basal and GnRH-stimulated LH secretion by pituitaries from GNX males in vitro. This inhibitory effect was blocked by the antagonist of RFRP receptors, RF9. In summary, our results support a putative inhibitory role of RFRP3 as ortholog of GnIH in the regulation of gonadotropin secretion in mammals, which appears to involve direct pituitary actions as well as potential central (hypothalamic) effects.

The effect of dry needling on gastrocnemius muscle stiffness and strength in participants with latent trigger points.

Abnormal muscle stiffness is a potential complication after injury and identifying interventions that modify muscle stiffness may be useful to promote recovery. The purpose of this study was to identify the short-term effects of dry needling (DN) on resting and contracted gastrocnemius muscle stiffness and strength of the triceps surae in individuals with latent myofascial trigger points (MTrPs). In this randomized controlled trial, 52 individuals received two DN treatment sessions to latent MTrPs and 50 individuals received two sham needling sessions. Resting and contracted muscle stiffness were assessed both at the treatment site and a standardized central site in the medial gastrocnemius head immediately post-treatment and one week after the last session. There were significant group by time interactions for resting muscle stiffness at the site of the MTrP (p = .03), but not at the central site (p = .29). Post-needling between group comparison indicated that the DN group had significantly lower resting muscle stiffness at the site of the MTrP than the sham group after adjusting for baseline differences. There were no significant between group differences in contracted muscle stiffness or muscle strength. Identifying strategies that can reduce aberrant muscle stiffness may help to guide management of individuals with neuromuscular pain-related conditions. Level of evidence: Therapy, level 2.

Novel expression and direct effects of adiponectin in the rat testis.

Adiponectin is an adipocyte hormone, with relevant roles in lipid metabolism and glucose homeostasis, recently involved in the control of different endocrine organs, such as the placenta, pituitary and, likely, the ovary. However, whether as described previously for other adipokines, such as leptin and resistin, adiponectin is expressed and/or conducts biological actions in the male gonad remains unexplored. In this study, we provide compelling evidence for the expression, putative hormonal regulation, and direct effects of adiponectin in the rat testis. Testicular expression of adiponectin was demonstrated along postnatal development, with a distinctive pattern of RNA transcripts and discernible protein levels that appeared mostly located at interstitial Leydig cells. Testicular levels of adiponectin mRNA were marginally regulated by pituitary gonadotropins but overtly modulated by metabolic signals, such as glucocorticoids, thyroxine, and peroxisome proliferator-activated receptor-gamma, whose effects were partially different from those on circulating levels of adiponectin. In addition, expression of the genes encoding adiponectin receptor (AdipoR)-1 and AdipoR2 was detected in the rat testis, with developmental changes and gonadotropin regulation for AdipoR2 mRNA, and prominent levels of AdipoR1 in seminiferous tubules. Moreover, recombinant adiponectin significantly inhibited basal and human choriogonadotropin-stimulated testosterone secretion ex vivo, whereas it failed to change relative levels of several Sertoli cell-expressed mRNAs, such as stem cell factor and anti-Müllerian hormone. In summary, our data are the first to document the expression, regulation and functional role of adiponectin in the rat testis. Taken together with its recently reported expression in the ovary and its effects on LH secretion and ovarian steroidogenesis, these results further substantiate a multifaceted role of adiponectin in the control of the reproductive axis, which might operate as endocrine integrator linking metabolism and gonadal function.

[A pilot study of endoscopic experimental transgastric peritoneoscopy and endoscopic gastrorrhaphy in a canine model.]. / Estudio piloto de endoscopia experimental:peritoneoscopia transgástrica y gastrorrafiaendoscópica en modelo canino.

BACKGROUND AND AIMS: Natural Orifice Translumenal Endoscopic Surgery (NOTES) is an experimental technique with potential advantages compared to laparoscopic surgery. Trans gastric peritoneoscopy (TP) is a NOTES technique. The aim of this study was to perform TP, to evaluate feasibility and technical limitations in a survival model. MATERIALS AND METHODS: The following procedures were performed in 4 anesthetized dogs using a single channel video gastroscope: Gastrotomy with needle-knife puncture followed with extension of the incision with a pull-type sphincterotome,pneumoperitoneum with the endoscope,peritoneoscopy and gastrorrhapy using hemoclips and endoloops. RESULTS: All the procedures were accomplished successfully with a mean duration of 80 minutes. Gastrotomy induced minor bleeding.Peritoneal cavity was accessed safely and peritoneoscopy was accomplished without incidents.Retroflexed maneuvers were mandatory to visualize upper abdomen and overinflation oftenly occurred. The closure of the gastric wall incision was successfully obtained. All the animals made an uncomplicated recovery after 7 days. CONCLUSIONS: TP is technically feasible and safe in a canine model. This study highlights several technical limitations and confirms the need for technological development.

[Meniscal transplant: clinical and functional experience at one year follow-up]. / Trasplante de menisco: experiencia con seguimiento clínico y funcional a un año.

INTRODUCTION: In Mexico, the first meniscus transplant was performed in 2002. The objective was to describe the clinical evolution of patients with pain associated with postmenisectomy syndrome, who underwent meniscal allograft transplantation (MAT), with bony blocks via arthroscopy, with follow-up to one year. MATERIAL AND METHODS: A retrospective cohort study with a one-year follow-up was conducted. We included patients with joint interlining pain secondary to partial or total menisectomy, between 15 and 55 years of age, of both sexes, who underwent MAT. The clinical evolution was evaluated with visual analogue scale (VAS), SF-36 and Lysholm scale; the results are described in frequencies, percentages and p value was significant at 0.05. RESULTS: We included nine patients; eight men and one woman with an age of 31.3 years (16-52), the follow-up was 16.6 months (12-23). The preoperative VAS was 8.5 (6-10) and, at one year of follow-up, the average of this scale was 1.25 (0-5) (p 0.001). In the follow-up one year after the MAT, the Lysholm scale was on average 91 (68-100) and the SF-36 was on average 79.17 (65-92.92); three patients returned to their sports practice prior to the injury. CONCLUSION: This is the first report in Mexico that describes the one year follow-up of the MAT; significant clinical improvement was demonstrated (p 0.001) with remission of pain in the knee with previous menisectomy and in some cases the return to sports practice.

INTRODUCCIÓN: En México se realizó el primer trasplante de menisco en 2002. El objetivo fue describir la evolución clínica de pacientes con dolor asociado al síndrome postmeniscectomía que fueron sometidos a trasplante de menisco alogénico (MAT), con bloques óseos vía artroscópica con seguimiento a un año. MATERIAL Y MÉTODOS: Se realizó un estudio de cohorte retrospectiva con seguimiento a un año; se incluyeron pacientes con dolor en interlínea articular secundario a meniscectomía parcial o total, entre 15 y 55 años de edad, de ambos sexos, que fueron sometidos a MAT. La evolución clínica se evaluó con EVA, SF-36 y escala de Lysholm; los resultados se describen en frecuencias, porcentajes y valor de p significativa 0.05. RESULTADOS: Se incluyeron nueve pacientes; ocho hombres y una mujer con edad de 31.3 años (16-52), el seguimiento fue de 16.6 meses (12-23). La EVA prequirúrgica fue de 8.5 (6-10) y al año de seguimiento el promedio de esta escala fue de 1.25 (0-5) (p 0.001). En el seguimiento a un año posterior al MAT, la escala de Lysholm fue en promedio de 91 (68-100) y la SF-36 fue en promedio de 79.17 (65-92.92); tres pacientes regresaron a su práctica deportiva previa a la lesión. CONCLUSIÓN: Éste es el primer reporte en México del seguimiento a un año del MAT; se demostró mejoría clínica significativa (p 0.001) con remisión del dolor en la rodilla con meniscectomía previa y en algunos casos el retorno a la práctica deportiva.

Neuromedin s as novel putative regulator of luteinizing hormone secretion.

Neuromedin S (NMS), a 36 amino acid peptide structurally related to neuromedin U, was recently identified in rat brain as ligand for the G protein-coupled receptor FM4/TGR-1, also termed neuromedin U receptor type-2 (NMU2R). Central expression of NMS appears restricted to the suprachiasmatic nucleus, and NMS has been involved in the regulation of dark-light rhythms and suppression of food intake. Reproduction is known to be tightly regulated by metabolic and photoperiodic cues. Yet the potential contribution of NMS to the control of reproductive axis remains unexplored. We report herein analyses of hypothalamic expression of NMS and NMU2R genes, as well as LH responses to NMS, in different developmental and functional states of the female rat. Expression of NMS and NMU2R genes was detected at the hypothalamus along postnatal development, with significant fluctuations of their relative levels (maximum at prepubertal stage and adulthood). In adult females, hypothalamic expression of NMS (which was confined to suprachiasmatic nucleus) and NMU2R significantly varied during the estrous cycle (maximum at proestrus) and was lowered after ovariectomy and enhanced after progesterone supplementation. Central administration of NMS evoked modest LH secretory responses in pubertal and cyclic females at diestrus, whereas exaggerated LH secretory bursts were elicited by NMS at estrus and after short-term fasting. Conversely, NMS significantly decreased elevated LH concentrations of ovariectomized rats. In summary, we provide herein novel evidence for the ability of NMS to modulate LH secretion in the female rat. Moreover, hypothalamic expression of NMS and NMU2R genes appeared dependent on the functional state of the female reproductive axis. Our data are the first to disclose the potential implication of NMS in the regulation of gonadotropic axis, a function that may contribute to the integration of circadian rhythms, energy balance, and reproduction.

Enhancing sensory experiences for very preterm infants in the NICU: an integrative review.

OBJECTIVE: Very preterm infants hospitalized in the neonatal intensive care unit (NICU) experience alterations in sensory experiences. Defining types, timing and frequency of sensory-based interventions that optimize outcomes can inform environmental modifications. The objective of this study was to conduct an integrative review on sensory-based interventions used with very preterm infants in the NICU to improve infant and parent outcomes. STUDY DESIGN: The data sources include MEDLINE, CINAHL, Cochrane Library and Google Scholar. Studies were identified that used sensory-based interventions in the NICU with preterm infants born ⩽32 weeks gestation, were published in a peer-reviewed journal between 1995 and 2015, and measured outcomes related to infant and parent outcomes. Studies were extracted from electronic databases and hand-searched from identified reference lists. RESULTS: Eighty-eight articles were identified (31 tactile, 12 auditory, 3 visual, 2 kinesthetic, 2 gustatory/olfactory and 37 multimodal). There was evidence to support the use of kangaroo care, music and language exposure, and multimodal interventions starting at 25 to 28 weeks postmenstrual age. These interventions were related to better infant development and lower maternal stress, but not all findings were consistent. Limitations included lack of consistent outcome measures, study quality and gaps in the literature. CONCLUSIONS: Most research identified interventions that were done for short periods of time. It is unclear what the potential is for improving outcomes if positive sensory exposures occur consistently throughout NICU hospitalization. Until more research defines appropriate sensory-based interventions to use with infants born very preterm in the NICU, information from this review can be combined with expert opinion and parent/family values to determine best practice.

A Direct Neurokinin B Projection from the Arcuate Nucleus Regulates Magnocellular Vasopressin Cells of the Supraoptic Nucleus.

Central administration of neurokinin B (NKB) agonists stimulates immediate early gene expression in the hypothalamus and increases the secretion of vasopressin from the posterior pituitary through a mechanism that depends on the activation of neurokinin receptor 3 receptors (NK3R). The present study reports that, in the rat, immunoreactivity for NK3R is expressed in magnocellular vasopressin and oxytocin neurones in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus, and that NKB immunoreactivity is expressed in fibres in close juxtaposition with vasopressin neurones at both of these sites. Retrograde tracing in the rat shows that some NKB-expressing neurones in the arcuate nucleus project to the SON and, in mice, using an anterograde tracing approach, it is found that kisspeptin-expressing neurones of the arcuate nucleus, which are known to co-express NKB, project to the SON and PVN. Finally, i.c.v. injection of the NK3R agonist senktide is shown to potently increase the electrical activity of vasopressin neurones in the SON in vivo with no significant effect detected on oxytocin neurones. The results suggest that NKB-containing neurones in the arcuate nucleus regulate the secretion of vasopressin from magnocellular neurones in rodents, and the possible significance of this is discussed.

Pattern of orexin expression and direct biological actions of orexin-a in rat testis.

Orexins, hypothalamic neuropeptides initially involved in the control of food intake and sleep-wake cycle, have recently emerged as pleiotropic regulators of different biological systems, including the reproductive axis. Besides central actions, peripheral expression and functions of orexins have been reported, and prepro-orexin and orexin type-1 receptor mRNAs have been detected in the testis. However, the pattern of expression and biological actions of orexin in the male gonad remain mostly unexplored. In this study, we report analyses on testicular prepro-orexin mRNA expression and orexin-A immunoreactivity in different experimental settings, and on direct effects of orexin-A on seminiferous tubule functions. Expression of prepro-orexin mRNA was demonstrated in the rat testis at different stages of postnatal development, with negligible levels at early juvenile period and maximum values in adulthood. Likewise, orexin-A immunoreactivity was demonstrated along postnatal maturation, with strong peptide signal in Leydig cells and spermatocytes at specific stages of meiosis. Testicular expression of prepro-orexin mRNA appeared hormonally regulated; its levels decreased after hypophysectomy and increased after gonadotropin replacement and ghrelin stimulation. Finally, orexin-A suppressed the expression of key Sertoli cell genes, such as Müllerian-inhibiting substance and stem cell factor, and inhibited DNA synthesis in specific stages of the seminiferous epithelium. In conclusion, we provide evidence for the regulated expression of orexin in the rat testis and its potential involvement in the control of seminiferous tubule functions. Together with our recent results on the expression of orexin type-1 receptor in the rat testis, our data further document a novel testicular site of action of orexins in the control of male reproductive axis.

Orexin 1 receptor messenger ribonucleic acid expression and stimulation of testosterone secretion by orexin-A in rat testis.

Orexins are hypothalamic neuropeptides primarily involved in the regulation of food intake and arousal states. In addition, a role for orexins as central neuroendocrine modulators of reproductive function has recently emerged. Prepro-orexin and orexin type-1 receptor mRNAs have been detected in the rat testis. This raises the possibility of additional peripheral actions of orexins in the control of reproductive axis, which remains so far unexplored. To analyze the biological effects and mechanisms of action of orexins in the male gonad, we evaluated testicular expression of orexin receptor 1 (OX(1)R) and orexin receptor 2 (OX(2)R) mRNAs in different experimental settings and the effect of orexin-A on testicular testosterone (T) secretion. Persistent expression of OX(1)R mRNA was demonstrated in the rat testis throughout postnatal development. In contrast, OX(2)R transcript was not detected at any developmental stage. Expression of OX(1)R mRNA persisted after selective elimination of mature Leydig cells and was detected in isolated seminiferous tubules at defined stages of the seminiferous epithelial cycle. In addition, testicular OX(1)R mRNA expression appeared to be under hormonal regulation; it was reduced by long-term hypophysectomy and partially restored by FSH replacement, whereas down-regulation was observed after exposure to increasing doses of the ligand in vitro. Moreover, OX(1)R mRNA expression was sensitive to neonatal imprinting by estrogen. Finally, orexin-A, in a dose-dependent manner, significantly increased basal, but not human choriogonadotropin-stimulated, T secretion in vitro. A similar stimulatory effect was observed in vivo after intratesticular administration of orexin-A. In conclusion, our present results provide the first evidence for the regulated expression of OX(1)R mRNA and functional role of orexin-A in the rat testis. Overall, our data are suggestive of a novel site of action of orexins in the control of male reproductive axis.