Altered corticosteroid metabolism differentially affects pituitary corticotropin response

Hanafusa, Junko; Mune, Tomoatsu; Tanahashi, Tetsuya; Isomura, Yukinori; Suwa, Tetsuya; Isaji, Mako; Daido, Hisashi; Morita, Hiroyuki; Murayama, Masanori

doi:10.1152/ajpendo.00065.2001

Cited by 10 publications

(6 citation statements)

References 30 publications

(37 reference statements)

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“…It has been reported that administration of GA decreases CRH release into the hypophysial portal blood without changing circulating glucocorticoid levels [13]. In this regard, Hanafusa et al [12] found that mRNA expression and the levels of CRH in the hypothalamus did not change in GA-treated rats. This study, however, demonstrated up-regulation of CRH receptor mRNA and binding levels in the pituitary of the GA-treated animals, suggesting that GA enhanced the ACTH response to CRH by increasing the number and/or sensitivity of CRH receptors.…”

Section: Discussionmentioning

confidence: 96%

“…A recent study showed alterations in the pituitaryadrenal response in vivo in rats treated with GA [12]. On the basis of this result we carried out CRH tests to investigate the course of pseudoaldosteronism.…”

Section: Discussionmentioning

confidence: 96%

“…A high dose of glucocorticoids usually suppresses ACTH production in the pituitary. Therefore, cortisol increased locally following the inhibition of 11b-HSD type 2 may induce either mild insensitivity of the receptor or weak suppression of the adrenal glands [12], which in turn alters the cortisol response in pseudoaldosteronism. Alternatively, the ACTH receptor or steroidogenetic enzymes may be modulated in GA-treated adrenal glands.…”

Section: Discussionmentioning

confidence: 99%

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A Case of Pseudoaldosteronism, Accompanied with Hypocalcemia and Exaggerated ACTH Response

et al. 2004

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Abstract. Glycyrrhizic acid (GA) inhibits the activity of 11b-hydroxysteroid dehydrogenase type 2 in the kidney, with the resulting increase in intrarenal cortisol concentration leading to hypertension and suppression of the renin-aldosterone system. In this paper we describe an interesting case of pseudoaldosteronism, associated with hypocalcemia and an exaggerated ACTH response. A 72-year-old woman was referred to our department for further evaluation of hypokalemia and hypocalcemia. The patient had been taking GA (150 mg/day) for the previous year for treatment of liver damage. Plasma renin activity and aldosterone concentration were both within lower normal limits. Urinary excretion of potassium and calcium was within the upper limit of the normal range and increased with administration of supplements. Plasma ACTH levels increased markedly in response to an intravenous injection of CRH. Cessation of GA and the potassium and calcium supplements on admission, led to a gradual normalization of serum potassium and calcium levels and blood pressure. The hypocalcaemia in our patient was related to decreased tubular reabsorption of calcium as a consequence of renal corticoid excess. It is possible that an increase in the number of CRH receptors in the pituitary following GA treatment caused the exaggerated ACTH response in association with pseudoaldosteronism. The existence of hypocalcemia and an exaggerated ACTH response should be observed carefully when managing pseudoaldosteronism. GLYCYRRHIZIC acid (GA) inhibits the activity of 11b-hydroxysteroid dehydrogenase (11b-HSD) type 2, an enzyme that inactivates cortisol and allows selective access to the aldosterone receptor [1,2]. The increased intrarenal concentration of cortisol resulting from inhibition of this enzyme causes stimulation of the mineralocorticoid receptor, leading to hypertension, hypokalemia, and suppression of the reninaldosterone system. As a consequence of these changes administration of GA causes pseudoaldosteronism [3]. A decrease in serum calcium concentration and increased urinary calcium excretion have been reported in primary aldosteronism and in glucocorticoid-treated patients [4,5]. Significant changes in renal calcium handling in healthy volunteers have also been demonstrated following inhibition of 11b-HSD type 2 by GA [6].We describe an interesting case of pseudoaldosteronism, accompanied with hypocalcemia and an exaggerated ACTH response. The hypocalcemia and the exaggerated ACTH response to CRH both improved in parallel with normalization of hypokalemia and the renin-aldosterone system. These findings indicate that the hypocalcemia was related to decreased tubular reabsorption of calcium under conditions of renal corticoid excess [6]. We also speculate on the mechanism responsible for the exaggerated ACTH response in this case of pseudoaldosteronism.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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A Case of Pseudoaldosteronism, Accompanied with Hypocalcemia and Exaggerated ACTH Response

et al. 2004

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“…81 In cases of long term hypothyroidism which can lead to hypoadrenalism and decreased cortisol levels, hydrocortisone (5 mg twice a day) or licorice (240 mg glycyrrhizin twice a day) may be efficacious. 82 Both hydrocortisone and licorice should be given upon rising and around noon to mimic the natural circadian rhythm. As licorice can lead to blood pressure elevation in some users, blood pressure monitoring is recommended while following this protocol.…”

Section: To T 3 Conversionmentioning

confidence: 99%

Fibromyalgia, Thyroid Dysfunction and Treatment Modalities

Friedman¹

2013

j restorat med

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Fibromyalgia is a debilitating condition presenting with symptoms of chronic muscular pain, fatigue, insomnia and cognitive dysfunction among other symptoms, which lead to a diminished quality of life. Although the exact pathogenesis and underlying mechanisms which lead to clinical manifestation are unknown, there is a growing line of evidence suggesting an association between fibromyalgia and thyroid dysfunction. Numerous studies have reported that patients with fibromyalgia have a high incidence of hypothyroidism. Further, thyroid autoimmunity has also been associated with fibromyalgia symptom severity. Circulating thyroid hormones do not provide an accurate status of thyroid function in patients with fibromyalgia, rather intracellular thyroid hormone levels are more relevant. Low levels of intracellular hormones may result from mitochondrial dysfunction as active transport of hormones across cellular membranes is required. It is well known that mitochondrial dysfunction is associated with fibromyalgia. In order to correct thyroid dysfunction and manage symptoms presenting in fibromyalgia patients, a multi-disciplinary approach should be taken incorporating dietary supplements, nutraceuticals, dietary changes and complementary alternative therapies.

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“…In contrast, 11HSD2 operates as a strict dehydrogenase that oxidizes corticosterone and cortisol to 11-oxo-derivatives [7]. 11HSD1 is expressed in the brain [8]–[10], pituitary [11], [12], adrenal gland [13], and many peripheral organs including the spleen, thymus, and lymphatic nodes [14], [15].…”

Section: Introductionmentioning

confidence: 99%

Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 and 7α-Hydroxylase CYP7B1 during Social Stress

et al. 2014

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11β-hydroxysteroid dehydrogenase type 1 (11HSD1) is an enzyme that amplifies intracellular glucocorticoid concentration by the conversion of inert glucocorticoids to active forms and is involved in the interconversion of 7-oxo- and 7-hydroxy-steroids, which can interfere with the activation of glucocorticoids. The presence of 11HSD1 in the structures of the hypothalamic-pituitary-adrenal (HPA) axis suggests that this enzyme might play a role in the regulation of HPA output. Here we show that the exposure of Fisher 344 rats to mild social stress based on the resident-intruder paradigm increased the expression of 11HSD1 and CYP7B1, an enzyme that catalyzes 7-hydroxylation of steroids. We found that social behavioral profile of intruders was significantly decreased whereas their plasma levels of corticosterone were increased more than in residents. The stress did not modulate 11HSD1 in the HPA axis (paraventricular nucleus, pituitary, adrenal cortex) but selectively upregulated 11HSD1 in some regions of the hippocampus, amygdala and prelimbic cortex. In contrast, CYP7B1 was upregulated not only in the hippocampus and amygdala but also in paraventricular nucleus and pituitary. Furthermore, the stress downregulated 11HSD1 in the thymus and upregulated it in the spleen and mesenteric lymphatic nodes whereas CYP7B1 was upregulated in all of these lymphoid organs. The response of 11HSD1 to stress was more obvious in intruders than in residents and the response of CYP7B1 to stress predominated in residents. We conclude that social stress induces changes in enzymes of local metabolism of glucocorticoids in lymphoid organs and in brain structures associated with the regulation of the HPA axis. In addition, the presented data clearly suggest a role of 11HSD1 in modulation of glucocorticoid feedback of the HPA axis during stress.

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Altered corticosteroid metabolism differentially affects pituitary corticotropin response

Cited by 10 publications

References 30 publications

A Case of Pseudoaldosteronism, Accompanied with Hypocalcemia and Exaggerated ACTH Response

A Case of Pseudoaldosteronism, Accompanied with Hypocalcemia and Exaggerated ACTH Response

Fibromyalgia, Thyroid Dysfunction and Treatment Modalities

Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 and 7α-Hydroxylase CYP7B1 during Social Stress

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