Angela Leal

... Bilezikjian LM, Corrigan AZ, Mellon PL & Vale WW. Activin-A modulates gonadotropin-releasing hormone secretion from a gonadotropin-releasing hormone-secreting neuronal cell line. Neuroendocrinology 1991; 54: 373–7. ... 20 Schubert D, Kimura H, LaCorbiere M, Vaughan J ...

This study was designed to evaluate the effects of glucocorticoids and gonadal steroids on the expression of inhibin/activin subunits and follistatin of the anterior pituitary and test the hypothesis that resulting changes in the local activin/inhibin/follistatin tone contribute to steroid effects on follicle stimulating hormone (FSH) production from gonadotropes. In primary cell cultures of male rat anterior pituitaries, dexamethasone (DEX) or testosterone (T) stimulated FSH secretion and FSHbeta mRNA and their effects were additive with activin-A. Follistatin (FS288) and inhibin-A antagonized the rise in FSH secretion both in the absence and presence of exogenous activin-A. Despite the similarity in their action on FSH production, DEX and T had opposite effects on follistatin mRNA levels. Follistatin mRNA levels of cultured rat anterior pituitary cells were elevated upon the addition of DEX but attenuated by T. On the other hand, both DEX and T suppressed inhibin/activin betaB mRNA levels while only DEX affected betaA mRNA. In these cells, activin-A stimulated follistatin and inhibin/activin betaB mRNA levels but had no effect on betaA. Together, DEX and activin-A caused a further increase in follistatin mRNA levels while T attenuated the effect of activin-A alone. Both steroids attenuated the effect of activin-A on betaB mRNA accumulation. These results support the possibility that DEX and T, possibly acting on different subsets of anterior pituitary cells, use distinct mechanisms to modify the local activin/inhibin/follistatin circuitry and thereby upregulate FSH production from the anterior pituitary gonadotropes.

Betaglycan was reported by our laboratory to serve as an inhibin binding protein and to facilitate the antagonism of activin signaling. Although an accessory receptor for TGFbeta and inhibin, its distribution within reproductive tissues remains largely unexplored. Histochemical analyses reveal betaglycan protein and mRNA distributed throughout the rat reproductive axis. In the brain, betaglycan mRNA is localized in discrete regions of the forebrain and brain stem, including olfactory, septal, and hypothalamic nuclei. In the pituitary, moderate levels of betaglycan protein and mRNA were observed in the anterior and intermediate lobes. Betaglycan immunoreactivity was colocalized with all the pituitary cell subtypes, to the greatest extent with the gonadotrope population. In the gonads, betaglycan mRNA was localized in cellular compartments, coinciding with its protein for the most part. Moderate levels of mRNA were observed in ovarian granulosa cells, with lower expression in the thecal layer and the oocyte. In the testes, betaglycan mRNA was observed in the Leydig and tubule-specific germ cells. This is the first comprehensive report detailing the distribution of betaglycan in mammalian reproductive tissues. The present findings illustrate and support the hypothesis of a modulatory role for betaglycan in TGFbeta and/or inhibin effects in these tissues.

... Bilezikjian LM, Corrigan AZ, Mellon PL & Vale WW. Activin-A modulates gonadotropin-releasing hormone secretion from a gonadotropin-releasing hormone-secreting neuronal cell line. Neuroendocrinology 1991; 54: 373–7. ... 20 Schubert D, Kimura H, LaCorbiere M, Vaughan J ...

This study was designed to evaluate the effects of glucocorticoids and gonadal steroids on the expression of inhibin/activin subunits and follistatin of the anterior pituitary and test the hypothesis that resulting changes in the local activin/inhibin/follistatin tone contribute to steroid effects on follicle stimulating hormone (FSH) production from gonadotropes. In primary cell cultures of male rat anterior pituitaries, dexamethasone (DEX) or testosterone (T) stimulated FSH secretion and FSHbeta mRNA and their effects were additive with activin-A. Follistatin (FS288) and inhibin-A antagonized the rise in FSH secretion both in the absence and presence of exogenous activin-A. Despite the similarity in their action on FSH production, DEX and T had opposite effects on follistatin mRNA levels. Follistatin mRNA levels of cultured rat anterior pituitary cells were elevated upon the addition of DEX but attenuated by T. On the other hand, both DEX and T suppressed inhibin/activin betaB mRNA levels while only DEX affected betaA mRNA. In these cells, activin-A stimulated follistatin and inhibin/activin betaB mRNA levels but had no effect on betaA. Together, DEX and activin-A caused a further increase in follistatin mRNA levels while T attenuated the effect of activin-A alone. Both steroids attenuated the effect of activin-A on betaB mRNA accumulation. These results support the possibility that DEX and T, possibly acting on different subsets of anterior pituitary cells, use distinct mechanisms to modify the local activin/inhibin/follistatin circuitry and thereby upregulate FSH production from the anterior pituitary gonadotropes.

Betaglycan was reported by our laboratory to serve as an inhibin binding protein and to facilitate the antagonism of activin signaling. Although an accessory receptor for TGFbeta and inhibin, its distribution within reproductive tissues remains largely unexplored. Histochemical analyses reveal betaglycan protein and mRNA distributed throughout the rat reproductive axis. In the brain, betaglycan mRNA is localized in discrete regions of the forebrain and brain stem, including olfactory, septal, and hypothalamic nuclei. In the pituitary, moderate levels of betaglycan protein and mRNA were observed in the anterior and intermediate lobes. Betaglycan immunoreactivity was colocalized with all the pituitary cell subtypes, to the greatest extent with the gonadotrope population. In the gonads, betaglycan mRNA was localized in cellular compartments, coinciding with its protein for the most part. Moderate levels of mRNA were observed in ovarian granulosa cells, with lower expression in the thecal layer and the oocyte. In the testes, betaglycan mRNA was observed in the Leydig and tubule-specific germ cells. This is the first comprehensive report detailing the distribution of betaglycan in mammalian reproductive tissues. The present findings illustrate and support the hypothesis of a modulatory role for betaglycan in TGFbeta and/or inhibin effects in these tissues.

We performed studies in 8-, 16-, 24-, 30 and 35-day-old Wistar rats at 8.00 h (AM) and 20.00 h (PM) to investigate the relationship between the diurnal variations of basal plasma corticosterone (compound B, CB) and its responses to ACTH and ether stress during the postnatal period. Basal plasma CB levels increased at PM from 8 to 35 days of age and an AM-PM difference was observed at 16 days. Although an AM-PM difference in CB responsiveness to ACTH was detected only at 24 and 35 days, ACTH induced an increasingly higher CB response at PM than at AM from 8 to 35 days. A stress-induced CB response was observed starting at 8 days of age and presented an age-dependent increase; however, no AM-PM difference was observed at any age. The stress-induced CB levels were higher than ACTH-induced CB values at all ages tested except at PM in 8-day old rats. These data demonstrate that the basal CB levels and adrenal sensitivity to ACTH rise during the evening as a function of neonatal development.

Daytime restriction of food availability phase-shifts the diurnal periodicity of plasma corticosterone (B) concentration in rats. However, the changes at the various functional levels in the hypothalamic-pituitary-adrenal (HPA) axis are not completely understood. We performed studies in two groups of Wistar rats, a control group with free access to food and a food-restricted group with access to food only from 09.00 to 11.00 h for 14 days. The basal plasma B and ACTH concentrations in the control group presented diurnal variation with higher values in the afternoon than in the morning. In the food-restricted group there was a 12-hour shift of peak B values. Plasma ACTH levels were high in the morning, but there was no significant difference between morning and afternoon values. Plasma AVP presented no diurnal variation in the control group. In the food-restricted group, the diurnal variations of plasma AVP and ACTH-B did not coincide. There was no detectable nycthemeral variation of pituitary ACTH or hypothalamic CRH and AVP contents in either group. Plasma ACTH did not exhibit any diurnal variation in response to CRH in free-fed or food-restricted rats anesthetized with chlorpromazine-morphine-pentobarbital. The administration of ACTH (1-24) resulted in higher B levels in the afternoon in control rats pretreated with dexamethasone once or twice. In the food-restricted group there was a 12-hour shift in the adrenal response to ACTH (1-24). These patterns of response were abolished in both groups when the rats were anesthetized. An in vitro study showed no diurnal variation in adrenal responsiveness to 10(-6) M-10(-9) M ACTH (1-24) stimuli. Our results suggest that anesthesia-related neural or humoral factor(s) other than ACTH are involved in the diurnal periodicity of the HPA axis in free-fed rats and in its shifts in food-restricted rats.

Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.

We performed studies in 8-, 16-, 24-, 30 and 35-day-old Wistar rats at 8.00 h (AM) and 20.00 h (PM) to investigate the relationship between the diurnal variations of basal plasma corticosterone (compound B, CB) and its responses to ACTH and ether stress during the postnatal period. Basal plasma CB levels increased at PM from 8 to 35 days of age and an AM-PM difference was observed at 16 days. Although an AM-PM difference in CB responsiveness to ACTH was detected only at 24 and 35 days, ACTH induced an increasingly higher CB response at PM than at AM from 8 to 35 days. A stress-induced CB response was observed starting at 8 days of age and presented an age-dependent increase; however, no AM-PM difference was observed at any age. The stress-induced CB levels were higher than ACTH-induced CB values at all ages tested except at PM in 8-day old rats. These data demonstrate that the basal CB levels and adrenal sensitivity to ACTH rise during the evening as a function of neonatal development.

Daytime restriction of food availability phase-shifts the diurnal periodicity of plasma corticosterone (B) concentration in rats. However, the changes at the various functional levels in the hypothalamic-pituitary-adrenal (HPA) axis are not completely understood. We performed studies in two groups of Wistar rats, a control group with free access to food and a food-restricted group with access to food only from 09.00 to 11.00 h for 14 days. The basal plasma B and ACTH concentrations in the control group presented diurnal variation with higher values in the afternoon than in the morning. In the food-restricted group there was a 12-hour shift of peak B values. Plasma ACTH levels were high in the morning, but there was no significant difference between morning and afternoon values. Plasma AVP presented no diurnal variation in the control group. In the food-restricted group, the diurnal variations of plasma AVP and ACTH-B did not coincide. There was no detectable nycthemeral variation of pituitary ACTH or hypothalamic CRH and AVP contents in either group. Plasma ACTH did not exhibit any diurnal variation in response to CRH in free-fed or food-restricted rats anesthetized with chlorpromazine-morphine-pentobarbital. The administration of ACTH (1-24) resulted in higher B levels in the afternoon in control rats pretreated with dexamethasone once or twice. In the food-restricted group there was a 12-hour shift in the adrenal response to ACTH (1-24). These patterns of response were abolished in both groups when the rats were anesthetized. An in vitro study showed no diurnal variation in adrenal responsiveness to 10(-6) M-10(-9) M ACTH (1-24) stimuli. Our results suggest that anesthesia-related neural or humoral factor(s) other than ACTH are involved in the diurnal periodicity of the HPA axis in free-fed rats and in its shifts in food-restricted rats.

Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.

We performed studies in 8-, 16-, 24-, 30 and 35-day-old Wistar rats at 8.00 h (AM) and 20.00 h (PM) to investigate the relationship between the diurnal variations of basal plasma corticosterone (compound B, CB) and its responses to ACTH and ether stress during the postnatal period. Basal plasma CB levels increased at PM from 8 to 35 days of age and an AM-PM difference was observed at 16 days. Although an AM-PM difference in CB responsiveness to ACTH was detected only at 24 and 35 days, ACTH induced an increasingly higher CB response at PM than at AM from 8 to 35 days. A stress-induced CB response was observed starting at 8 days of age and presented an age-dependent increase; however, no AM-PM difference was observed at any age. The stress-induced CB levels were higher than ACTH-induced CB values at all ages tested except at PM in 8-day old rats. These data demonstrate that the basal CB levels and adrenal sensitivity to ACTH rise during the evening as a function of neonatal development.

Daytime restriction of food availability phase-shifts the diurnal periodicity of plasma corticosterone (B) concentration in rats. However, the changes at the various functional levels in the hypothalamic-pituitary-adrenal (HPA) axis are not completely understood. We performed studies in two groups of Wistar rats, a control group with free access to food and a food-restricted group with access to food only from 09.00 to 11.00 h for 14 days. The basal plasma B and ACTH concentrations in the control group presented diurnal variation with higher values in the afternoon than in the morning. In the food-restricted group there was a 12-hour shift of peak B values. Plasma ACTH levels were high in the morning, but there was no significant difference between morning and afternoon values. Plasma AVP presented no diurnal variation in the control group. In the food-restricted group, the diurnal variations of plasma AVP and ACTH-B did not coincide. There was no detectable nycthemeral variation of pituitary ACTH or hypothalamic CRH and AVP contents in either group. Plasma ACTH did not exhibit any diurnal variation in response to CRH in free-fed or food-restricted rats anesthetized with chlorpromazine-morphine-pentobarbital. The administration of ACTH (1-24) resulted in higher B levels in the afternoon in control rats pretreated with dexamethasone once or twice. In the food-restricted group there was a 12-hour shift in the adrenal response to ACTH (1-24). These patterns of response were abolished in both groups when the rats were anesthetized. An in vitro study showed no diurnal variation in adrenal responsiveness to 10(-6) M-10(-9) M ACTH (1-24) stimuli. Our results suggest that anesthesia-related neural or humoral factor(s) other than ACTH are involved in the diurnal periodicity of the HPA axis in free-fed rats and in its shifts in food-restricted rats.

Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.

To evaluate the feasibility of 8 months of supervised exercise therapy in warm water and its effects on the impact of fibromyalgia on physical and mental health and physical fitness in affected women. Thirty women with fibromyalgia were randomly assigned to an exercise therapy group (n = 15) or a control group (inactive) (n = 15). The impact of fibromyalgia on physical and mental health was assessed using the Fibromyalgia Impact Questionnaire and the anxiety state with State-Trait Anxiety Inventory. Physical fitness was measured using the following tests: Canadian Aerobic Fitness; hand-grip dynamometry; 10-metre walking; 10-step stair-climbing and blind 1-leg stance. After 8 months of training, the exercise therapy group improved compared with the control group in terms of physical function (20%), pain (8%), stiffness (53%), anxiety (41%), depression (27%), Fibromyalgia Impact Questionnaire total scores (18%), State-Trait Anxiety Inventory score (22%), aerobic capacity (22%), balance (30%), functional capacity for walking (6%), stair-climbing with no extra weight (14%) and stair-climbing 10 kg-weighted (25%). Eight months of supervised exercise in warm water was feasible and led to long-term improvements in physical and mental health in patients with fibromyalgia at a similar magnitude to those of shorter therapy programmes.