Persona: Collado Guirao, Paloma
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Publicación Genistein early in life modifies the arcuate nucleus of the hypothalamus morphology differentially in male and female rats(Elsevier, 2023) Fernández García, José Manuel; Tezanos, Patricia; Pino Osuna, María José; Carrillo Urbano, Beatriz; Collado Guirao, PalomaIn the present work we analyzed the effects of postnatal exposure to two doses of genistein (10 μg/g or 50 μg/g) from postnatal (P) day 6 to P13, on the morphology of the arcuate nucleus (Arc). The analyses of Arc coronal brain sections at 90 days showed that the ArcMP had higher values in volume, Nissl-stained neurons and GPER-ir neurons in males than in females and the treatment with genistein abolished these sex differences in most of the parameters studied. Moreover, in males, but not in females, the GPER-ir neurons decreased in the ArcMP but increased in the ArcL with both doses of genistein. In the ArcLP, GPER-ir population increased with the lowest doses and decreased with the highest one in males. Our results confirm that the Arc subdivisions have differential vulnerability to the effects of genistein during development, depending on which neuromorphological parameters, dose and sex are analyzed.Publicación Neonatal inhibition of androgen activity alters the programming of body weight and orexinergic peptides differentially in male and female rats(Elsevier, 2024-02-13) Fernández García, José Manuel; Grassi, Daniela; Blanco, Noemí; Ballesta, Antonio; Arevalo, María de los Ángeles; Pino Osuna, María José; Carrillo Urbano, Beatriz; García Úbeda, Rocío; Primo Chulvi, Ulises; Collado Guirao, PalomaThe involvement of androgens in the regulation of energy metabolism has been demonstrated. The main objective of the present research was to study the involvement of androgens in both the programming of energy metabolism and the regulatory peptides associated with feeding. For this purpose, androgen receptors and the main metabolic pathways of testosterone were inhibited during the first five days of postnatal life in male and female Wistar rats. Pups received a daily s.c. injection from the day of birth, postnatal day (P) 1, to P5 of Flu- tamide (a competitive inhibitor of androgen receptors), Letrozole (an aromatase inhibitor), Finasteride (a 5- alpha-reductase inhibitor) or vehicle. Body weight, food intake and fat pads were measured. Moreover, hypo- thalamic Agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay. The inhibition of androgenic activity during the first five days of life produced a significant decrease in body weight in females at P90 but did not affect this parameter in males. Moreover, the inhibition of aromatase decreased hypothalamic AgRP mRNA levels in males while the inhibition of 5α-reductase decreased hypothalamic AgRP and orexin mRNA levels in female rats. Finally, food intake and visceral fat, but not subcutaneous fat, were affected in both males and females depending on which testosterone metabolic pathway was inhibited. Our results highlight the differential involvement of androgens in the programming of energy metabolism as well as the AgRP and orexin systems during development in male and female ratsPublicación G Protein-Coupled Estrogen Receptor Immunoreactivity Fluctuates During the Estrous Cycle and Show Sex Differences in the Amygdala and Dorsal Hippocampus(Frontiers Media, 2020) Llorente, Ricardo; Marraudino, Marilena; Bonaldo, Brigitta; Simon Areces, Julia; Abellanas Pérez, Pedro; Rivero Aguilar, Marina; Fernández García, José Manuel; Pino Osuna, María José; Garcia Segura, Luis Miguel; Grassi, Daniela; Carrillo Urbano, Beatriz; Collado Guirao, PalomaG protein-coupled estrogen receptor (GPER) in the amygdala and the dorsal hippocampus mediates actions of estradiol on anxiety, social recognition and spatial memory. In addition, GPER participates in the estrogenic regulation of synaptic function in the amygdala and in the process of adult neurogenesis in the dentate gyrus. While the distribution of the canonical estrogen receptors α and β in the amygdala and dorsal hippocampus are well characterized, little is known about the regional distribution of GPER in these brain regions and whether this distribution is affected by sex or the stages of the estrous cycle. In this study we performed a morphometric analysis of GPER immunoreactivity in the posterodorsal medial, anteroventral medial, basolateral, basomedial and central subdivisions of the amygdala and in all the histological layers of CA1 and the dentate gyrus of the dorsal hippocampal formation. The number of GPER immunoreactive cells was estimated in these different structures. GPER immunoreactivity was detected in all the assessed subdivisions of the amygdaloid nucleus and dorsal hippocampal formation. The number of GPER immunoreactive cells was higher in males than in estrus females in the central (P = 0.001) and the posterodorsal medial amygdala (P < 0.05); higher in males than in diestrus females in the strata orients (P < 0.01) and radiatum-lacunosum-moleculare (P < 0.05) of CA1-CA3 and in the molecular layer of the dentate gyrus (P < 0.01); higher in diestrus females than in males in the basolateral amygdala (P < 0.05); higher in diestrus females than in estrus females in the central (P < 0.01), posterodorsal medial (P < 0.01) and basolateral amygdala (P < 0.01) and higher in estrus females than in diestrus females in the strata oriens (P < 0.05) and radiatum-lacunosum-moleculare (P < 0.05) of CA1-CA3 and in the molecular layer (P < 0.05) and the hilus of the dentate gyrus (P < 0.05). The findings suggest that estrogenic regulation of the amygdala and hippocampus through GPER may be different in males and in females and may fluctuate during the estrous cycle.Publicación Exposure to increased levels of estradiol during development can have long-term effects on the response to undernutrition in female rats(Taylor and Francis Group, 2016-11) Díaz, Francisca; Chowen, Julie A.; Pino Osuna, María José; Carrillo Urbano, Beatriz; Collado Guirao, PalomaObjectives: Undernutrition during development alters the expression of peptides that control energy expenditure and feeding behavior. Estrogens can also modulate these peptides. Here we analyzed whether early postnatal administration of estradiol modulates the effects of undernutrition on neuroendocrine parameters in adult female Wistar rats. Methods: Control rats were fed a control diet. Undernourished pups were submitted to a restricted diet with half of the undernourished rats receiving 0.4 mg/kg s.c. of estradiol benzoate (EB) from postnatal day (P) 6 until P13. Quantitative real-time PCR was performed to determine expression in the hypothalamus of Agouti-related peptide (AgRP), proopiomelanocortin (POMC), neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART). Plasma estradiol, testosterone and adiponectin levels were measured by ELISA. Total and acylated ghrelin levels were measured in plasma by RIA. Results: Undernourishment decreased body weight, fat mass, plasma leptin and insulin levels and hypothalamic POMC mRNA levels. An increase in orexigenic signals AgRP and NPY mRNA levels, and in plasma adiponectin levels were found in undernourished animals. Early postnatal treatment with EB to undernourished female rats reversed the effects of undernutrition on adult hypothalamic POMC mRNA levels. In addition, neonatal EB treatment to undernourished females significantly decreased adult plasma testosterone, estradiol and acylated ghrelin levels. Discussion: Our results suggest that increased estradiol during a critical period of development has the capacity to modulate the alterations that undernutrition produces on energy metabolism.Publicación Blocking of Estradiol Receptors ERα, ERβ and GPER During Development, Differentially Alters Energy Metabolism in Male and Female Rats(Elsevier, 2020) Díaz González, Francisca; Chowen, Julie A.; Grassi, Daniela; Pinos Sánchez, Helena; Carrillo Urbano, Beatriz; Collado Guirao, PalomaEstradiol not only participates in the regulation of energy metabolism in adulthood, but also during the first stages of life as it modulates the alterations induced by under- and over-nutrition. The objectives of the present study were to determine: 1) If estradiol is involved in the normal programming of energy metabolism in rats; 2) If there is a specific window of time for this programming and 3) If males and females are differentially vulnerable to the action of this hormone. Estrogen receptors (ER) α, ERβ and GPER were blocked by their specific antagonists MPP, PHTPP and G15, respectively, from postnatal day (P) 1 (the day of birth) to P5 or from P5 to P13. Physiological parameters such as body weight, fat depots and caloric intake were then analysed at P90. Hypothalamic AgRP, POMC, MC4R, ERα, ERβ and GPER mRNA levels and plasma levels of estradiol, were also studied. We found that blocking ER receptors from P5 to P13 significantly decreases long-term body weight in males and hypothalamic POMC mRNA levels in females. The blocking of ERs from P1 to P5 only affected plasma estradiol levels in females. The present results indicate programming actions of estradiol from P5 to P13 on body weight in male and POMC expression in female rats and emphasize the importance of including both sexes in metabolic studies. It is necessary to unravel the mechanisms that underlie the actions of estradiol on food intake, both during development and in adulthood, and to determine how this programming differentially takes place in males and females.Publicación Neonatal inhibition of androgen activity alters the programming of body weight and orexinergic peptides differentially in male and female rats(Elsevier, 2024-02-13) Fernández García, José Manuel; Grassi, Daniela; Blanco, Noemí; Ballesta, Antonio; Arevalo, María de los Ángeles; Pino Osuna, María José; Carrillo Urbano, Beatriz; García Úbeda, Rocío; Primo Chulvi, Ulises; Collado Guirao, PalomaThe involvement of androgens in the regulation of energy metabolism has been demonstrated. The main objective of the present research was to study the involvement of androgens in both the programming of energy metabolism and the regulatory peptides associated with feeding. For this purpose, androgen receptors and the main metabolic pathways of testosterone were inhibited during the first five days of postnatal life in male and female Wistar rats. Pups received a daily s.c. injection from the day of birth, postnatal day (P) 1, to P5 of Flu- tamide (a competitive inhibitor of androgen receptors), Letrozole (an aromatase inhibitor), Finasteride (a 5- alpha-reductase inhibitor) or vehicle. Body weight, food intake and fat pads were measured. Moreover, hypo- thalamic Agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay. The inhibition of androgenic activity during the first five days of life produced a significant decrease in body weight in females at P90 but did not affect this parameter in males. Moreover, the inhibition of aromatase decreased hypothalamic AgRP mRNA levels in males while the inhibition of 5α-reductase decreased hypothalamic AgRP and orexin mRNA levels in female rats. Finally, food intake and visceral fat, but not subcutaneous fat, were affected in both males and females depending on which testosterone metabolic pathway was inhibited. Our results highlight the differential involvement of androgens in the programming of energy metabolism as well as the AgRP and orexin systems during development in male and female ratsPublicación Exposure to increased levels of estradiol during development can have long-term effects on the response to undernutrition in female rats(Taylor and Francis Group, 2016-11) Díaz González, Francisca; Chowen, Julie A.; Pino Osuna, María José; Carrillo Urbano, Beatriz; Collado Guirao, PalomaObjectives: Undernutrition during development alters the expression of peptides that control energy expenditure and feeding behavior. Estrogens can also modulate these peptides. Here we analyzed whether early postnatal administration of estradiol modulates the effects of undernutrition on neuroendocrine parameters in adult female Wistar rats. Methods: Control rats were fed a control diet. Undernourished pups were submitted to a restricted diet with half of the undernourished rats receiving 0.4 mg/kg s.c. of estradiol benzoate (EB) from postnatal day (P) 6 until P13. Quantitative real-time PCR was performed to determine expression in the hypothalamus of Agouti-related peptide (AgRP), proopiomelanocortin (POMC), neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART). Plasma estradiol, testosterone and adiponectin levels were measured by ELISA. Total and acylated ghrelin levels were measured in plasma by RIA. Results: Undernourishment decreased body weight, fat mass, plasma leptin and insulin levels and hypothalamic POMC mRNA levels. An increase in orexigenic signals AgRP and NPY mRNA levels, and in plasma adiponectin levels were found in undernourished animals. Early postnatal treatment with EB to undernourished female rats reversed the effects of undernutrition on adult hypothalamic POMC mRNA levels. In addition, neonatal EB treatment to undernourished females significantly decreased adult plasma testosterone, estradiol and acylated ghrelin levels. Discussion: Our results suggest that increased estradiol during a critical period of development has the capacity to modulate the alterations that undernutrition produces on energy metabolism.Publicación Genistein during Development Alters Differentially the Expression of POMC in Male and Female Rats(MDPI, 2021) Fernández García, José Manuel; Tezanos, Patricia; Pino Osuna, María José; Carrillo Urbano, Beatriz; Collado Guirao, PalomaPhytoestrogens are considered beneficial for health, but some studies have shown that they may cause adverse effects. This study investigated the effects of genistein administration during the second week of life on energy metabolism and on the circuits regulating food intake. Two different genistein doses, 10 or 50 g/g, were administered to male and female rats from postnatal day (P) 6 to P13. Physiological parameters, such as body weight and caloric intake, were then analyzed at P90. Moreover, proopiomelanocortin (POMC) expression in the arcuate nucleus (Arc) and orexin expression in the dorsomedial hypothalamus (DMH), perifornical area (PF) and lateral hypothalamus (LH) were studied. Our results showed a delay in the emergence of sex differences in the body weight in the groups with higher genistein doses. Furthermore, a significant decrease in the number of POMC-immunoreactive (POMC-ir) cells in the Arc in the two groups of females treated with genistein was observed. In contrast, no alteration in orexin expression was detected in any of the structures analyzed in either males or females. In conclusion, genistein can modulate estradiol’s programming actions on the hypothalamic feeding circuits differentially in male and female rats during development.