Effect of stress on hepatic 11beta-hydroxysteroid dehydrogenase activity and its influence on carbohydrate metabolism.

Stress activates the synthesis and secretion of catecholamines and adrenal glucocorticoids, increasing their circulating levels. In vivo, hepatic 11beta-hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11-dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at tissue level. We studied the effect of 3 types of stress, 1 induced by bucogastric overload with 200 mmol/L HCl causing metabolic acidosis (HCl), the second induced by bucogastric overload with 0.45% NaCl (NaCl), and the third induced by simulated overload (cannula), on the kinetics of hepatic HSD1 of rats and their influence on the activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, glycemia, and glycogen deposition. Compared with unstressed controls, all types of stress significantly increased HSD1 activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29% cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68% NaCl, and 78% HCl). Owing to these results, we suggest the following events occur when stress is induced: an increase in hepatic HSD1 activity, augmented active glucocorticoid levels, increased gluconeogenesis, and glycemia. Also involved are the multiple events indirectly related to glucocorticoids, which lead to the depletion of hepatic glycogen deposits, thereby contributing to increased glycemia. This new approach shows that stress increments the activity of hepatic HSD1 and suggests that this enzyme could be involved in the development of the Metabolic Syndrome.

Adrenal gland involvement in the regulation of renal 11beta-hydroxysteroid dehydrogenase 2.

Renal 11beta-hydroxysteroid dehydrogenase 2 (HSD2) catalyzes the conversion of active glucocorticoids to inert 11beta-keto compounds, thereby preventing the illicit binding of these hormones to mineralocorticoid receptors (MRs) and, thus, conferring aldosterone specificity. Absence or inhibition of HSD2 activity, originates a hypertensive syndrome with sodium retention and increased potassium elimination. Recent studies from our laboratory reported an increment of HSD2 activity in intact-stressed rats. To evaluate the adrenal involvement in this increase, we analyzed HSD2 activity and protein abundance in Intact, Sham-operated, and adrenalectomized rats under stress situations (gavage with an overload of 200 mM HCl (10 ml) and simulated gavage) or with corticosterone replacement. HSD2 activity was assessed in renal microsomal preparations obtained from different groups of animals. HSD2 protein abundance was measured by Western-blot. Circulating corticosterone was determined by radioimmunoassay. Sham-operated animals showed an increase in HSD2 activity and abundance compared to Intact and adrenalectomized rats suggesting the involvement of stress-related adrenal factors in HSD2 regulation. In the case of acidotic adrenalectomized animals, there was an increase in renal HSD2 activity when, along with the HCl overload, the rats were injected with corticosterone. This increment occurred without an increase in enzyme abundance. These results suggest the importance of circulating levels of glucocorticoids to respond to a metabolic acidosis, through regulation of HSD2 stimulation. The group subjected to a simulated gavage showed an increase in enzyme activity and protein abundance, thus demonstrating the need for both adrenal and extra-factors in the modulation of renal HSD2. The adrenalectomized animals injected with different doses of corticosterone, produced a progressive increase in enzyme activity and abundance, being significant for the dose of 68 microg corticosterone/100 g body weight. The highest dose (308 microg/100 g body weight) did not show any variation in activity and abundance compared to the control group. This biphasic effect of glucocorticoids could be explained taking into account their permissive and suppressive actions, depending on their blood levels. Knowing that stress induces multifactorial responses, it should not be surprising to observe a differential regulation in renal HSD2, confirming that different stressors act through different factors of both, adrenal and extra-adrenal origin.

Effects of chronic treatments with adrenal steroids on acid-base homeostasis in the rat

Urinary parameters related to acid base homeostasis were studied in adrenalectomized rats (ADX) as well as in ADX treated with physiological doses of corticosterone (B), aldosterone (aldo) or 18-Hydroxycorticosterone (l8HOB) during 1,3 or 5 days, under basal conditions and after gravage with 200 mM HCI. The results showed: a) a persistent effect of B and l8HOB increasing titratable acidity principally in response to acidosis; b) an increased phosphate elimination in acidotic B treated ADX on the first day, and in 18 HOB treated ADX on days 3 and 5; c) pronounced increases in blood pH and blood bicarbonate levels provoked by the three steroids on day 1; d) increments of ammonium elimination in response to acidosis by aldo treatmets on the first day, while B and l8HOB increase ammonium elimination under almost all conditions during the whole experiment; e) the effects of B and 18 HOB would be independent of an increase in sodium retention as well as glomerular filtration rate.

Effects of chronic treatments with adrenal steroids on acid-base homeostasis in the rat

Urinary parameters related to acid base homeostasis were studied in adrenalectomized rats (ADX) as well as in ADX treated with physiological doses of corticosterone (B), aldosterone (aldo) or 18-Hydroxycorticosterone (l8HOB) during 1,3 or 5 days, under basal conditions and after gravage with 200 mM HCI. The results showed: a) a persistent effect of B and l8HOB increasing titratable acidity principally in response to acidosis; b) an increased phosphate elimination in acidotic B treated ADX on the first day, and in 18 HOB treated ADX on days 3 and 5; c) pronounced increases in blood pH and blood bicarbonate levels provoked by the three steroids on day 1; d) increments of ammonium elimination in response to acidosis by aldo treatmets on the first day, while B and l8HOB increase ammonium elimination under almost all conditions during the whole experiment; e) the effects of B and 18 HOB would be independent of an increase in sodium retention as well as glomerular filtration rate. (AU)

In vitro uptake of 18-hydroxycorticosterone by regions of the central nervous system

Estudiamos la unión específica de la 18-hidroxicorticosterona (18-OH-B) a fracciones nucleares y citoplasmáticas de células provenientes de bulbo, protuberancia, amígdala, pituitaria anterior, hipotálamo, hipocampo, área preóptica y pulmón de animales adrenalectomizados, después de incubar los tejidos con el ligando radiactivo. Encontramos que 18-OH-B tiene una mayor unión específica a núcleos obtenidos de bulbo y protuberancia; este perfil difiere de observaciones previas en las que otros corticosteroide íntimamente relacionados, como la corticosterona y la aldosterona, se encuentran principalmente concentrados en el sistema límbico

In vitro uptake of 18-hydroxycorticosterone by regions of the central nervous system

Estudiamos la unión específica de la 18-hidroxicorticosterona (18-OH-B) a fracciones nucleares y citoplasmáticas de células provenientes de bulbo, protuberancia, amígdala, pituitaria anterior, hipotálamo, hipocampo, área preóptica y pulmón de animales adrenalectomizados, después de incubar los tejidos con el ligando radiactivo. Encontramos que 18-OH-B tiene una mayor unión específica a núcleos obtenidos de bulbo y protuberancia; este perfil difiere de observaciones previas en las que otros corticosteroide íntimamente relacionados, como la corticosterona y la aldosterona, se encuentran principalmente concentrados en el sistema límbico (AU)

Corticosterone secretion by rats after adrenalectomy

Se determinaron los niveles plasmáticos de corticosteroma de ratas en diferentes períodos después de la adrenalectomía, utilizando cromatografía líquida de alta presión (HPLC) y/o cromatografía gas-líquido (GLC). Se encontraron niveles mínimos 24 a 48 horas después de la operación

Corticosterone secretion by rats after adrenalectomy

Se determinaron los niveles plasmáticos de corticosteroma de ratas en diferentes períodos después de la adrenalectomía, utilizando cromatografía líquida de alta presión (HPLC) y/o cromatografía gas-líquido (GLC). Se encontraron niveles mínimos 24 a 48 horas después de la operación (AU)