Developmental and functional effects of steroid hormones on the neuroendocrine axis and spinal cord

This review highlights the principal effects of steroid hormones at central and peripheral levels in the neuroendocrine axis. The data discussed highlight the principal role of oestrogens and testosterone in hormonal programming in relation to sexual orientation, reproductive and metabolic programming, and the neuroendocrine mechanism involved in the development of polycystic ovary syndrome phenotype. Moreover, consistent with the wide range of processes in which steroid hormones take part, we discuss the protective effects of progesterone on neurodegenerative disease and the signalling mechanism involved in the genesis of oestrogen-induced pituitary prolactinomas.Fil: Zubeldia Brenner, Lautaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Roselli, C. E.. Oregon Health and Science University Portland; Estados UnidosFil: Recabarren, S. E.. Universidad de Concepción; ChileFil: Gonzalez Deniselle, Maria Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lara, H. E.. Universidad de Chile; Chil

A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections

Indexación: Scopus.A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1⁻32 μg/mL against Gram-positive ATCC® strains. The structure⁻activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16, were the MIC50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.https://www.mdpi.com/1420-3049/23/7/177

Impacto de la exposición prenatal a testosterona sobre parámetros biométricos y endocrinos en ovinos recién nacidos

Biometric and endocrine parameters were studied in male and female Suffolk Down newborn lambs born to mothers exposed to an excess of testosterone (EPT) during 60 days (EPT-P1) and during 90 days (EPT-P2), beginning at day 30 of pregnancy. Control mothers received vegetable oil. At delivery time the following data were registered: time of delivery, number of newborns per mother and sex of the newborn. At 8 hours postpartum, the characteristics of the genitalia, the anus-urinary meatus distance and body weight were recorded. Blood samples were taken to measure cortisol, T3 and T4 on plasma. Data regarding time of birth, number of offspring and sex did not show any differences between the three groups of newborn lambs. Females born to EPT-P1 and EPT-P2 mothers exhibited masculinized genitalia, showing a penis and an empty scrotum. Females born to EPT-P1 mothers showed lower body weight and lower plasma T4 concentrations than females and males born to the other 2 groups of mothers (P < 0.05). Plasma cortisol concentrations were not different between offspring from the 3 groups of mothers, however, females born to EPT-P1 mothers showed an inverse correlation between cortisol concentration and body weight. Data showed that exposure to testosterone during a critical time during pregnancy had a profound impact on genitalia of females, and depending on the dose it produces lower body weight and lower plasma T4 concentrations in newborn females. The EPT had no effect on biometric and endocrine parameters in newborn male lambs.  Se estudiaron parámetros biométricos y endocrinos de crías recién nacidas de ovejas Suffolk Down expuestas prenatalmente a un exceso de testosterona (EPT) durante 60 días (EPT-P1, n = 16) y 90 días (EPT-P2, n = 12), a partir del día 30 de preñez. Las madres control (n =32) recibieron aceite vegetal. Al momento del parto se registraron: hora del parto, número de crías por madre y sexo de las crías. Ocho horas postparto se registraron: las características de los genitales externos, distancia ano-meato urinario (DAM) y peso corporal. Se determinó concentración plasmática de cortisol, T3 y T4, por radioinmunoensayo. Hora del parto, número y sexo de las crías fue similar entre los grupos. Las hembras nacidas de madres con EPT-P1 y EPT-P2 exhibieron genitales masculinizados con presencia de un pene y un escroto vacío. Las hembras nacidas de madres EPT-P1 presentaron menor peso al nacimiento que las hembras y machos control y hembras nacidas de madres EPT-P2 (P < 0,05), DAM semejante a los machos (P<0,01) y menor concentración de T4 que los otros grupos (P<0,05). Además presentaron una relación inversa entre cortisol plasmático y peso corporal. Las hembras nacidas de madres EPT-P2, con excepción de la masculinización de los genitales, no se diferenciaron de las hembras nacidas de madres control. Los parámetros biométricos y endocrinos de los machos no mostraron diferencias entre los tres grupos. Concluimos que la EPT produce masculinización de los genitales de hembras y, dependiendo de la concentración de testosterona, la EPT puede disminuir las concentraciones plasmáticas de T4 en las hembras. La EPT no influye en parámetros biométricos y endocrinos de machos recién nacidos. &nbsp

Ovarian morphometry and mRNA expression of antimüllerian hormone (AMH), follicle stimulating hormone receptor (FSHR) and nuclear factor kappa B (NFkB) in growing follicles of female lambs prenatally exposed to testosterone.

Artículo de publicación SciELOAntenatal exposure to testosterone (T) has a series of consequences on postnatal reproductive parameters in females of several animal species. In sheep born under this condition the ovaries are characterized by an increased number of growing follicles. If such disruptions are manifested early in life or involve changes in follicular recruitment and ovary paracrine environment, it remains unclear. This study addressed the impact of prenatal T on ovarian morphometry and the mRNA expression of ovarian anti-müllerian hormone (AMH), FSH receptor (FSHR) and nuclear factor kappa B (NFkB, a transcription factor for AMH), factors that are involved in the growth and selection of the dominant follicle. At 4 weeks of age, female lambs born to dams treated with 30 mg of T propionate twice weekly from day 30 to day 90, followed by 40 mg of T propionate from day 90 to day 120 of pregnancy (T females), showed similar number of primordial, primary, secondary and antral follicles than control females (C females) born to dams treated with the vehicle. In the pool of secondary follicles (< 0.5 mm) the expression of the FSHR was slightly higher in the T females, while AMH and NFkB expression were lower than C females. Instead, the pool of small antral follicles (between 0.5 and 1 mm) showed a higher expression of FSHR and a slight increase in AMH in T females, while NFkB expression remained lower than C females. These findings provide evidence that the prenatal exposure to T impacts the expression of key local factors governing the folliculogenesis before histological alterations occur.Financiado por proyecto Fondecyt 109003

Sensibilidad a la insulina en ovejas prepúberes con alimentación normal y con restricción alimenticia

It has been shown that fasting in growing ewes is associated with insulin resistance as an adaptative mechanism to the low energy supply. Food restriction is another experimental or natural situation that may occur for growing ewes where energy supply is under the requirement for growth. Insulin sensitivity may also change as a physiological adaptation to the shortage of food. The aim of the present study was to assess if insulin sensitivity decreases during food restriction in growing ewes. Insulin sensitivity was assessed by the intravenous glucose tolerance test (IVGTT). A glucose solution (300mg/kg body weight, 50% solution) was infused over two minutes into five normal growing 26-week old ewes and five 26 week-old ewes that had been restrictively fed from the age of 20 to 26 weeks. Blood samples were collected from the jugular vein of each ewe by an indwelling jugular vein catheter 15 and 10 min before and at 0, 3, 5, 7, 10, 13, 15, 17, 20, 23, 25, 27 and 30 min after the initiation of the glucose infusion, and plasma glucose and insulin were measured by RIA. To determine the insulin sensitivity index (ISI), glucose and insulin concentrations were analyzed using the Matsuda and De Fronzo's formula (ISI-Composite). Basal, stimulated and incremental area under the curve of insulin and the glucose utilization constants were also calculated. ISI-C was lower in food-restricted female sheep (636.43&nbsp;±&nbsp;125.66) compared to normal growing females (1528.18&nbsp;±&nbsp;297.61), (P&nbsp;&lt;&nbsp;0.05). Concordant with this, incremental area under the curve of insulin was lower (290.54&nbsp;±&nbsp;79.45 ng/ml/30 min) in control than in food-restricted females (642.16&nbsp;±&nbsp;140.04 ng/mL/30 min, P&nbsp;&lt;&nbsp;0.05). The glucose utilization constant did not differ between groups. Results suggest that food restriction induces insulin resistance as an adaptative process to the shortage of food in growing female sheep.Se ha demostrado, en borregas en crecimiento, que el ayuno está asociado a resistencia insulínica como un fenómeno adaptativo a la baja ingesta calórica. La restricción alimenticia&nbsp;es otra situación natural o experimental que puede enfrentar la hembra en crecimiento, en la cual la disponibilidad de energía está por debajo de los requerimientos indispensables para el crecimiento. La sensibilidad a la insulina podría cambiar también como una adaptación fisiológica a la escasez de alimento. El objetivo del presente estudio fue reconocer si la sensibilidad a la insulina disminuye durante la restricción alimenticia de borregas en crecimiento. La sensibilidad a la insulina se evaluó con el test de tolerancia a la glucosa endovenosa (TTGEV). Cinco borregas con crecimiento normal y cinco borregas con restricción alimenticia por seis semanas, a partir de las 20 semanas de edad, se infundieron con una solución estéril de glucosa (300 mg/kg peso corporal, solución al 50%) en dos minutos. Se colectaron muestras de sangre desde la yugular mediante un catéter venoso 15 y 10 minutos antes de la infusión de glucosa, y a los 0, 3, 5, 7, 10, 13, 15, 17, 20, 23, 25, 27, 30 minutos después del inicio de la infusión en cuyo plasma se midió glucosa e insulina. Las concentraciones de glucosa (g/l) e insulina (µUI/ml) se analizaron con la fórmula de Matsuda y DeFronzo para determinar el índice de sensibilidad a la insulina (ISI-Composite). Se calculó también el área bajo la curva de insulina basal, estimulada e incremental y la constante de utilización de la glucosa. El ISI-C fue menor en las borregas con restricción alimenticia (636,43± 125,66) en comparación con las borregas controles (1528,18 ± 297,61 P&lt;0,05). En concordancia con estos resultados, el área bajo la curva incremental fue menor en las borregas controles (290,54 ± 79,45 ng/ml/30 min) que en las con restricción alimenticia (642,16 ± 140,04 ng/mL/30 min, P&lt;0,05). La constante de utilización de la glucosa fue similar en ambos grupos. Los resultados sugieren que la restricción alimenticia conduce a una resistencia insulínica como un proceso adaptativo a la escasa provisión de alimento en la oveja en crecimiento

Polycystic ovary syndrome

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.Robert J Norman, Ruijin Wu and Marcin T Stankiewic

Secreción pulsátil diurna de la hormona foliculo estimulante (FSH) en ovejas prepúberes con y sin restriccion alimenticia

Food restriction delays the onset of puberty due to a low secretion of LH and probably the FSH as well. The objective of this work was to assess and to compare the diurnal pulsatile secretion of FSH in normal growing and in growth-retarded ewe lambs due to food restriction. Five Suffolk ewe lambs were fed at 2% of their body weight in two daily rations whereas the other 5 were fed ad-libitum from 20 and until 30 weeks of age and served as a control group. A FSH pulsatile study was conducted, before and after six and ten weeks of food restriction corresponding to 20, 26 and 30 weeks of age respectively. The FSH pulsatile study consisted in collecting blood samples every 10 minutes for 5 hours from 10 AM onwards. In the obtained plasma the FSH was measured by RIA. The characteristics of the pulsatile FSH secretion were assessed using the CLUSTER program. Data obtained from the CLUSTER program were analyzed with analysis of variance for repeated measures. Mean plasma FSH concentrations (ng/mL/5h) increased in almost 50% in control ewe lambs between 20 and 30 weeks of age but without statistical difference. At 30 weeks of age, control lambs had a 50% higher mean plasma FSH concentrations and mean FSH pulse amplitude than food-restricted lambs. FSH pulse frequency did not show any difference between ages within a group or between groups. Results suggest that food restriction has a partial suppressor effect on the FSH secretion. The delay on the onset of puberty due to food-restriction in the ewe lamb could be attributed more to an insufficient LH secretion GnRH-stimulated than to an inadequate FSH secretion.La restricción alimenticia retarda el inicio de la pubertad, producto de una disminución de la secreción pulsátil de LH y probablemente de FSH. El objetivo del presente trabajo fue conocer y comparar la secreción pulsátil diurna de FSH entre borregas con crecimiento normal y con crecimiento retrasado, producido por la restricción alimenticia. Cinco borregas Suffolk se alimentaron al 2% de su peso corporal con alimento concentrado en dos raciones diarias, mientras que otras 5 se alimentaron a voluntad a partir de las 20 y hasta las 30 semanas de edad. A las 20, 26 y 30 semanas de edad, se realizó un estudio de pulsatilidad de FSH. Este estudio consistió en la colección de muestras de sangre cada 10 minutos desde las 10 AM, por cinco horas, en cuyo plasma se midió FSH por RIA . Las características de la secreción pulsátil durante las cinco horas del estudio se reconocieron por medio del programa computacional CLUSTER. Los datos se analizaron con Andeva para muestras repetidas. Las concentraciones plasmáticas promedio (ng/ mL/5h) aumentaron en alrededor de un 50% en las borregas controles, entre las 20 y 30 semanas de edad, pero sin significancia estadística. A las 30 semanas de edad, las borregas controles tenían una concentración promedio de FSH plasmática y una amplitud de pulsos un 50% más alta que en las borregas con restricción alimenticia. La secreción de FSH no aumentó estadísticamente entre las 20 y 30 semanas de edad en las borregas controles, mientras que tendió a disminuir en las borregas con restricción alimenticia. La frecuencia de pulsos de FSH no mostró diferencias entre las edades o entre los grupos. Los resultados sugieren que la restricción alimenticia tiene un efecto supresor parcial sobre la secreción de FSH durante el desarrollo prepuberal de la borrega. El retraso en el inicio de la pubertad, debido a restricción alimenticia en la borrega, se podría atribuir más bien a una insuficiente secreción de LH que a una deficiencia en la secreción de FSH. &nbsp

Análogo de GnRH disminuye la secreción de hormona folículo estimulante (FSH) en ovejas prepúberes

LH and FSH secretions depend on the pulsatile secretion of GnRH from the hypothalamus. However, the grade of dependency as well as the relationship between pulses of GnRH and pulses of FSH secretion is less clear. Experiments in monkeys have shown that high GnRH pulse frequency favors LH secretion while low frequency of GnRH pulses preferentially stimulates the FSH secretion. The objective of the present work was to recognize the dependence of GnRH on the FSH secretion in prepubertal female sheep. A GnRH agonist analogue in slow release microcapsule preparation was used (Trp6-GnRH, (Decapeptyl®)) whose blocking effect on the LH release has been previously demonstrated. The analogue was injected intramuscularly every 4 weeks beginning at 20 weeks of age three times in five Suffolk ewe lambs. Another group of five lambs received the vehicle of Decapeptyl. Studies of FSH pulsatility were carried out at 20 (before the analogue agonist administration), 26 and 30 weeks of age. The CLUSTER program was used to identify characteristics of FSH secretion: transversal mean (ng/ml/5h), frequency of pulses (number of pulses/5h), amplitude of pulses (ng/ml) and nadir (ng/ml) . In the control group, FSH secretion characteristics did not change between 20 and 30 weeks of age. In the experimental group, mean FSH concentrations decreased from 3.4±0.3 ng/ml/5h at 20 weeks of age to 0.36 ±0.1 ng/mL/ 5h at 30 weeks of age (P&lt;0,05), which was also significantly lower than in the control group of the same age. Amplitude of FSH pulses in lambs of 30 weeks of age were significantly lower than in lambs of 20 weeks of age (4.4 ± 0.5 versus 0.5 ± 0.1 ng/mL respectively, P&lt;0.05), and lower than that exhibited by control ewe lambs of 30 weeks of age. FSH pulse frequency did not change between lambs of 20 and 30 weeks of age in either group. Results show that the GnRH analogue is able to block the FSH secretion suggesting that the FSH secretion is dependant on GnRH stimulation in prepubertal female sheep.La secreción de LH y FSH depende de la liberación pulsátil de GnRH desde el hipotálamo; sin embargo, el grado de dependencia así como la relación entre los pulsos de GnRH y la secreción de FSH es menos clara. Experimentos en monos han mostrado que altas frecuencias de liberación de pulsos de GnRH estimulan preferentemente la secreción de LH, mientras que bajas frecuencias de pulsos de GnRH favorecen la secreción de FSH. Estudios sobre el control de la secreción de FSH en ovejas prepúberes son escasos. Con el objetivo de reconocer la dependencia de la secreción de FSH por parte de la GnRH, se administró un análogo de GnRH en microcápsulas de liberación lenta (Trp6-GnRH, Decapeptyl®) y cuyo efecto bloqueador sobre la secreción de LH ha sido demostrado. El análogo se administró intramuscularmente cada cuatro semanas a partir de las 20 semanas de edad a cinco borregas Suffolk por tres veces. Otro grupo de ovejas prepúberes de las mismas edades recibió el vehículo. Estudios de pulsatilidad de FSH se efectuaron a las, 20, 26 y 30 semanas de edad. Se utilizó el programa Cluster para reconocer las características de la secreción pulsátil de FSH. En las borregas del grupo control no hubo cambios en las características de la secreción pulsátil de FSH entre las 20 y 30 semanas de edad. En el grupo tratado con el análogo de GnRH, las concentraciones plasmáticas de FSH disminuyeron desde 3,4±0,3 ng/mL/5h a las 20 semanas de edad hasta los 0,36±0,1 ng/mL/5h a las 30 semanas de edad (p&lt;0,05), concentración significativamente menor que en el grupo control. La amplitud de los pulsos disminuyó desde 4,4 ± 0,5 a 0,5 ± 0,1 ng/mL a las 30 semanas de edad (p&lt;0,05), la cual fue menor que la exhibida por las borregas de la misma edad del grupo control. La frecuencia no cambió (2,5 ± 0,5 y 2,4 ± 0,2 pulsos/5h). Los resultados permiten concluir que el análogo de GnRH de liberación lenta es capaz de bloquear la secreción de FSH, lo que sugiere que la secreción de FSH es dependiente de GnRH en ovejas prepúberes. La frecuencia de pulsos de FSH no se modificó con el análogo de GnRH

Evaluación de la acción de un antagonista de receptores gabaérgicos sobre la secreción de hormona luteinizante, antes, durante y después de un ayuno en ovejas prepúberes

The objective of this study was to assess the effect of a GABA receptor antagonist, (Bicuculline) on the pulsatile LH secretion before, during and after fasting in ewe lambs. Five Suffolk ewe lambs of 20 weeks of age were subjected to fasting for 8 days. A study of LH pulsatility was performed before (day 0), after one and eight days of fasting and 48 hours after the end of fasting. This study consisted in collecting blood samples by means of an indwelling jugular vein catheter at 10 min intervals for 10 hours from 9am inwards hours. Five hours after the start of the pulsatility study, a bolus of Bicuculline (50 ug/kg BW) was given intravenously. Thus, the 10-hours study period was divided in two phases of 5-hours each: before and after bicuculline. Parameters of the LH secretion were determined by the CLUSTER program independently for both phases and compared by paired t-test. Basal parameters of LH secretion on each day of the study were analyzed with ANOVA for repeated measures and comparison of the means with the Newman Keulss test. Body weight was recorded and basal levels of blood glucose, insulin and cortisol were also obtained before, during and after fasting.&nbsp;Body weight and basal plasma glucose concentrations decreased significantly after 8 days of fasting, however, insulin and cortisol did not change. Parameters of pulsatile LH secretion did not change with fasting or after 48 hours of refeeding. Bicuculline tended to increase (p&lt;0.06) both mean plasma concentrations and amplitude of LH pulses before fasting (Day 0), but it had no effect on LH secretion on day 1, 8 of fasting or after two days of refeeding.&nbsp;Results suggest that GABA may be involved in the control of LH secretion in normally fed ewe lambs, however this control is not apparent during fasting. Fasting has an impact on body weight and plasma glucose concentrations but no effect on basal plasma levels of insulin. Plasma cortisol concentrations did not change suggesting that fasting did not evoke a stress condition.El propósito de este estudio fue establecer si la actividad gabaérgica forma parte de los mecanismos supresores de la secreción pulsátil de LH durante el ayuno en ovejas prepúberes. 5 borregas Suffolk de 20 semanas de edad fueron sometidas a un ayuno de 8 días. Se recolectaron muestras de sangre mediante un cáteter endovenoso para medir en su plasma las concentraciones de LH, un día antes del comienzo del ayuno (día 0), el primer día de ayuno (día 1), el ultimo día del ayuno (día 8) y 48 horas finalizado éste (día 10), cada 10 minutos, por cinco horas. Al término de las primeras 5 horas de muestreo se administró un pulso de bicuculina (50 ug/kg PV), un antagonista de receptores GABA-A, y se continuó el muestreo sanguíneo por otras cinco horas. Las características de la secreción pulsátil de LH se determinaron con el programa computacional Cluster. Se compararon las características de secreción de LH antes y después de la administración de bicuculina en los 4 días del ensayo empleando un test de t pareado para comparar entre períodos y Andeva para comparar entre días del ensayo.&nbsp;El peso vivo y las concentraciones plasmáticas basales de glucosa disminuyeron con el ayuno, mientras que las concentraciones plasmáticas de insulina y cortisol se mantuvieron sin cambios. El peso vivo y la glucosa plasmática se recuperaron significativamente con la realimentación. La administración de un pulso de Bicuculina tendió a aumentar la concentración plasmática promedio y la amplitud de los pulsos (p&lt;0.07) de LH, mientras que la frecuencia de pulsos y el nadir no cambiaron (p&gt;0.05)antes delayuno (día 0). Por el contrario, la administración de bicuculina no tuvo efecto sobre estos parámetros de secreción de LH durante los días 1, 8 y 10 del ensayo (p&gt;0.05).&nbsp;Los resultados sugieren que las vías GABAérgicas participarían en el control de la secreción de LH en ovejas prepúberes con alimentación normal, situación que no es demostrable durante el ayuno. La ausencia de cambios en las concentraciones basales de cortisol sugieren que el ayuno no activa reacciones de stress

Striatal responsiveness to reward under threat-of-shock and working memory load: A preliminary study.

Reward and stress are important determinants of motivated behaviors. Striatal regions play a crucial role in both motivation and hedonic processes. So far, little is known on how cognitive effort interacts with stress to modulate reward processes. This study examines how cognitive effort (load) interacts with an unpredictable acute stressor (threat-of-shock) to modulate motivational and hedonic processes in healthy adults. A reward task, involving stress with unpredictable mild electric shocks, was conducted in 23 healthy adults aged 20-37 (mean age: 24.7 ± 0.9; 14 females) during functional magnetic resonance imaging (fMRI). Manipulation included the use of (a) monetary reward for reinforcement, (b) threat-of-shock as the stressor, and (c) a spatial working memory task with two levels of difficulty (low and high load) for cognitive load. Reward-related activation was investigated in a priori three regions of interest, the nucleus accumbens (NAcc), caudate nucleus, and putamen. During anticipation, threat-of-shock or cognitive load did not affect striatal responsiveness to reward. Anticipated reward increased activation in the ventral and dorsal striatum. During feedback delivery, both threat-of-shock and cognitive effort modulated striatal activation. Higher working memory load blunted NAcc responsiveness to reward delivery, while stress strengthened caudate nucleus reactivity regardless reinforcement or load. These findings provide initial evidence that both stress and cognitive load modulate striatal responsiveness during feedback delivery but not during anticipation in healthy adults. Of clinical importance, sustained stress exposure might go along with dysregulated arousal, increasing therefore the risk for the development of maladaptive incentive-triggered motivation. This study brings new insight that might help to build a framework to understand common stress-related disorders, given that these psychiatric disorders involve disturbances of the reward system, cognitive deficits, and abnormal stress reactivity