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Matteo Baldi

Publications and source records attributed to Matteo Baldi.

4 recordsLinked to original sources
PubMed2005

Hypothalamus-pituitary-adrenal hyperactivity in human aging is partially refractory to stimulation by mineralocorticoid receptor blockade.

CONTEXT: The hypothalamus-pituitary-adrenal (HPA) axis is mainly regulated by CRH, arginine vasopressin, and glucocorticoid feedback. Hippocampal mineralocorticoid receptors mediate proactive glucocorticoid feedback and mineralocorticoid antagonists, accordingly, stimulate HPA axis. Age-related HPA hyperactivity reflects impaired glucocorticoid feedback at the suprapituitary level. DESIGN: ACTH, cortisol, and dehydroepiandrosterone (DHEA) secretion were studied in eight healthy elderly (75.1 +/- 3.2 yr) and eight young (25.0 +/- 4.6 yr) subjects during placebo or canrenoate (CAN) administration (200 mg i.v. bolus followed by 200 mg infused over 4 h). RESULTS: During placebo administration, ACTH and cortisol areas under the curve (AUCs) in elderly subjects were higher than in young subjects (P < or = 0.01); conversely, DHEA AUCs in elderly subjects were lower than in young subjects (P = 0.002). CAN increased ACTH, cortisol, and DHEA levels in both groups. In young subjects, ACTH, cortisol, and DHEA levels at the end of CAN infusion were higher (P < or = 0.05) than after placebo. In elderly subjects, at the end of CAN infusion, ACTH, cortisol, and DHEA levels were higher (P = 0.01) than after placebo. Under CAN, ACTH and cortisol AUCs were persistently higher (P < or = 0.01) and DHEA AUCs lower (P = 0.006) in elderly than in young subjects. Cortisol AUCs after CAN in young subjects did not become significantly different from those in elderly subjects after placebo. CONCLUSIONS: 1) Evening-time ACTH and cortisol secretion in elderly subjects is higher than in young subjects; 2) ACTH and cortisol secretion in elderly subjects is enhanced by CAN but less than that in young subjects; and 3) DHEA hyposecretion in elderly subjects is partially restored by mineralocorticoid antagonism. Age-related variations of HPA activity may be determined by some derangement in mineralocorticoid receptors function at the hippocampal level.

Adrenocorticotropic Hormone↗
PubMed2004

Ghrelin, hypothalamus-pituitary-adrenal (HPA) axis and Cushing's syndrome.

Ghrelin, a peptide predominantly produced by the stomach, has been discovered as a natural ligand of the GH Secretagogue receptor type 1a (GHS-R1a), known as specific for synthetic GHS. Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts pleiotropic actions that are explained by the widespread distribution of ghrelin and GHS-R expression. Besides strong stimulation of GH secretion, the neuroendocrine ghrelin actions also include significant stimulation of both lactotroph and corticotroph secretion; all these actions depend on acylation of ghrelin in serine-3 that allows binding and activation of the GHS-R1a. However, GHS-R subtypes are likely to exist; they also bind unacylated ghrelin that is, in fact, the most abundant circulating form and exerts some biological actions. Ghrelin secretion is mainly regulated by metabolic signals, namely inhibited by feeding, glucose and insulin while stimulated by energy restriction. The role of glucocorticoids on ghrelin synthesis and secretion is still unclear although morning ghrelin levels have been found reduced in some patients with Cushing's syndrome; this, however, would simply reflect its negative association to body mass. Ghrelin, like synthetic GHS, stimulates ACTH and cortisol secretion in normal subjects and this effect is generally sensitive to the negative glucocorticoid feedback. It is remarkable that, despite hypercortisolism, ghrelin as well as synthetic GHS display marked increase in their stimulatory effect on ACTH and cortisol secretion in patients with Cushing's disease. This is even more intriguing considering that the GH response to ghrelin and GHS is markedly reduced by glucocorticoid excess. It has been demonstrated that the ACTH-releasing effect of ghrelin and GHS is purely mediated at the central level in physiological conditions; its enhancement in the presence of ACTH-secreting tumours is, instead, likely to reflect direct action on GHS receptors present on the neoplastic tissues. In fact, peculiar ACTH hyperresponsiveness to ghrelin and GHS has been observed also in ectopic ACTH-secreting tumours.

Adrenocorticotropic Hormone↗
PubMed2004

Free fatty acids exert an inhibitory effect on adrenocorticotropin and cortisol secretion in humans.

Free fatty acid (FFA) administration stimulates the hypothalamic-pituitary-adrenal (HPA) axis in rats, suggesting that the HPA axis and lipolysis may be linked by a positive-feedback loop. To clarify the influence of FFA on the HPA axis in humans, we studied the effect of lipid load on both basal and stimulated ACTH and cortisol secretion in normal subjects. In six young female volunteers [(mean +/- SEM) age, 24.4 +/- 2.1 yr; body mass index, 23.1 +/- 1.2 kg/m(2)), ACTH, cortisol, FFA, glucose, and insulin levels were measured every 30 min for 330 min during the following procedures: 1) i.v. saline infusion (from 0 to 330 min); 2) i.v. FFA infusion (Intralipid 10%, from 0 to 210 min) followed by saline infusion (from 210 to 330 min); 3) human CRH (hCRH) administration (2 microg/kg i.v. at 90 min) during saline infusion (from 0 to 330 min); and 4) hCRH administration during FFA infusion (Intralipid 10%, from 0 to 210 min, followed by saline infusion from 210 to 330 min). During saline infusion, ACTH and cortisol levels progressively declined. Lipid-heparin emulsion (LHE) infusion strikingly increased circulating FFA levels and, simultaneously, amplified the ACTH and cortisol decrease (P < 0.05). After LHE withdrawal, FFA decrease was associated with an increase (P < 0.05) in ACTH and cortisol levels (restored to baseline values within 60 min). The ACTH and cortisol responses to hCRH, however, were unaffected by LHE that, concomitantly, induced an increase (P < 0.05) in glucose but not in insulin levels. This study shows that an LHE-induced increase in FFA levels has an inhibitory effect on spontaneous ACTH and cortisol secretion in humans. Lipid load, however, does not affect the ACTH and cortisol responses to hCRH; this evidence would indicate that the negative influence of FFA on the HPA axis in humans takes place at the suprapituitary level.

Adrenocorticotropic Hormone↗