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Biomedical subjects

E C degli Uberti

Publications and source records attributed to E C degli Uberti.

At least 19 recordsLinked to original sources
PubMed2006

Hypopituitarism findings in patients with primary brain tumors 1 year after neurosurgical treatment: preliminary report.

Hypopituitarism represents the consequence of many conditions, in both the adult and child population. It may occur after neurosurgical treatment of brain tumors arising near sella turcica. Much more attention has been focused on lesions far from the hypothalamic-pituitary region as possible causes of pituitary impairment, validating the concept of the particular fragility of these structures. The aim of this study was to evaluate pituitary function in particular GH deficiency (GHD) in patients submitted to neurosurgery for benign tumors of the central nervous system (CNS) not involving hypothalamic-pituitary region. We observed 37 patients with benign brain tumors [13 males, 24 females, age: 54.6+/-13.9 yr; body mass index (BMI): 25.1+/-4.0 kg/m2] performing a basic evaluation of the pituitary function and a dynamic test of the GH/IGF-I axis [GHRH (1 microg/kg iv)+arginine (0.5 g/kg iv) test] for 3 and 12 months after the neurosurgical treatment. Some degree of hypopituitarism was shown in 16 patients (43.2%) at the 3-months follow-up. Hypogonadism was present in 4 patients, hypoadrenalism in another 4 and hypothyroidism in 2. Two patients showed mild hyperprolactinemia and no patients had diabetes insipidus. Seven patients (18.9%) were GH deficient (peak GH <16.5 microg/dl). At 12 months retesting, some degree of hypopituitarism was confirmed in 8 patients, hypogonadism in 2 and hypothyroidism in one; no patients showed hypoadrenalism and GHD was present in 5. This data suggests that hypopituitarism of various degree may develop in patients who are submitted to neurosurgery for primary brain tumors, even far from hypothalamic-pituitary region.

Adult↗
PubMed2005

Dopamine receptor subtype 2 and somatostatin receptor subtype 5 expression influences somatostatin analogs effects on human somatotroph pituitary adenomas in vitro.

Dopamine (DA) and somatostatin (SRIF) receptor agonists inhibit growth hormone (GH) secretion by pituitary adenomas. We investigated DA subtype 2 receptor (DR2) and SRIF receptor (sst) subtypes 2 and 5 expression in 25 GH-secreting pituitary adenomas and tested in primary culture the effects on GH and prolactin (PRL) secretion of sst agonists selectively interacting with sst2 (BIM-23120), sst5 (BIM-23206), and sst2 and sst5 (BIM-23244). All adenomas expressed sst2; eight adenomas expressed both sst5 and DR2, eight sst5 but not DR2, and eight DR2 but not sst5. One tissue lacked expression of DR2 and sst5. GH secretion was inhibited by BIM-23120 in all samples, while it was reduced by BIM-23206 only in adenomas not expressing DR2. BIM-23120's inhibitory effects correlated with sst2 and DR2 expression, whereas DR2 expression correlated inversely with BIM-23206 inhibitory effects on GH secretion. In seven mixed GH-/PRL-secreting pituitary adenomas, PRL secretion was inhibited in sst5-expressing tumors by BIM-23206, but not by BIM-23120. BIM-23244 reduced PRL secretion only in adenomas expressing sst2, sst5 and DR2. sst5 and DR2 expression correlated directly with BIM23206 inhibitory effects on PRL secretion. Our results suggest that adenomas expressing DR2 are less likely to respond to clinically available SRIF analogs in terms of GH secretion inhibition. Therefore, drugs interacting also with DR2 might better control secretion of pituitary adenomas.

Acromegaly↗
PubMed2005

Review of Cortina criteria for the diagnosis of acromegaly.

Diagnostic protocols for acromegaly have evolved over time reflecting the refinement of assays for the biochemical assessment of the GH-IGF-I axis and greater understanding of disease process. In February 1999, an International Consensus Conference was held in Cortina, Italy, to define the criteria for cure of acromegaly. This review paper summarizes the diagnostic guidelines proposed in the consensus statement by Giustina et al. In recent years, however, the criteria for both biochemical assessment and long-term monitoring in patients with acromegaly have changed with the development of increasingly sensitive and specific GH assays coupled with the widespread availability of reliable IGF-I assays. For this reason, constant updating of the assessment criteria proposed in the workshop held in Cortina, in 1999, would be advisable.

Acromegaly↗
PubMed2004

Cerebral aneurysm and acromegaly: a case report.

Few cases are reported concerning the association between cerebral aneurysms and acromegaly, and this is the first case report documenting an increase in diameter of a cerebral aneurysm in persistent acromegaly. Persistently elevated GH plasma levels might promote an increase in diameter of cerebral aneurysms. An accurate follow-up in acromegalic patients is important, especially concerning the cerebrovascular system. Establishing the effectiveness and usefulness of this strategy will require future prospective studies.

Acromegaly↗
PubMed2004

Somatostatin receptors: from basic science to clinical approach--thyroid.

Somatostatin and its receptors are expressed in the thyroid gland, but somatostatin analogs which are currently available have provided contradictory results in the diagnosis and treatment of thyroid neoplasia. Somatostatin and its analogs fail to influence follicular thyroid function, whereas their administration in patients with medullary thyroid carcinoma induces a reduction of serum calcitonin concentrations and clinical symptoms, but fails to influence tumour size and patient survival rate. Radiolabelled somatostatin analogs can localise tumours expressing somatostatin receptors, but somatostatin receptor-targeted radiotherapy of thyroid malignancies has provided conflicting and inconclusive results. Our recent results indicate that somatostatin receptor 2 activation by somatostatin receptor 2 agonists inhibits cell proliferation in the human medullary thyroid carcinoma cell line, TT. This effect can be hampered by concurrent somatostatin receptor 5 selective agonist treatment, which fails to influence TT cell proliferation, suggesting an antagonism between somatostatin receptors 5 and 2 agonists in medullary thyroid carcinoma cells. Moreover, somatostatin receptors 2 or 5 agonists fail to inhibit calcitonin secretion and calcitonin gene expression. On the other hand, somatostatin receptor 1 agonists inhibit proliferation, calcitonin secretion and calcitonin gene expression in parafollicular C cells, suggesting that analogs with enhanced somatostatin receptor 1 affinity and selectivity besides having great potentiality as pharmacological tools to control neoplastic growth, may also be used to reduce symptoms in patients with medullary thyroid carcinoma.

Humans↗
PubMed2004

Somatostatin signal transduction in thyroid parafollicular C cells.

The effects of somatostatin (SRIF) through its receptors (SSTRs) has been explored in many tissues, and here we discuss the role of the SRIF-SSTR system in human parafollicular C cells, reporting recent data on the effects of selective SSTR agonists on parafollicular C cells, that suggest new therapeutic approaches for medical treatment of medullary thyroid carcinoma. Moreover, the possible pathways involved in SRIF signalling in parafollicular C cells are discussed.

Animals↗
PubMed2003

An in vivo OctreoScan-negative adrenal pheochromocytoma expresses somatostatin receptors and responds to somatostatin analogs treatment in vitro.

A 52-yr-old woman presented with hypertension, elevated urinary vanillylmandelic acid, metanephrines, normetanephrines, and plasma chromogranin A (CgA), but normal urinary catecholamine levels. Abdominal ultrasonography and subsequent MRI imaging showed a 3 cm nodular lesion of the right adrenal gland also visualized by 123I-meta-iodobenzylguanidine scintigraphy consistent with a pheochromocytoma (PC). Her OctreoScan was negative. The patient underwent right adrenalectomy and histological examination showed a PC. The adrenal medulla tissue was examined for somatostatin (SRIH) receptor subtypes 1 to 5 (SSTR1 to 5) expression by RT-PCR. Cultured tumor cells were treated with either SRIH, Lanreotide (Lan), or an SSTR2 (BIM-23 120) or SSTR5 (BIM-23 206) selective agonist. CgA secretion was measured in the medium by ELISA and catecholamine levels by HPLC after 6h. Cell viability was assessed after 48h. RT-PCR analysis showed that SSTR1, 2, 3 and 4 were expressed. CgA secretion was significantly reduced by SRIH (- 80 %), Lan (- 35 %), and the SSTR2 selective agonist (- 65 %). Norepinephrine secretion was reduced by SRIH (- 66 %), Lan (- 40 %), and BIM-23 120 (- 70 %). Epinephrine and dopamine secretion was also inhibited by treatment with SRIH (- 90 % and - 93 %, respectively) and BIM-23 120 (- 33 % and - 75 %, respectively) but not by Lan. Cell viability was also significantly reduced by SRIH (- 30 %), Lan (- 10 %), and the SSTR2 selective agonist (- 20 %). The SSTR5 selective agonist did not modify either CgA and catecholamine secretion or cell viability. Our data show that SSTRs may be present in a PC although OctreoScan is negative in vivo, and that SRIH and its analogs may reduce both differentiated and proliferative functions in chromaffin cells in vitro. These findings suggest that SRIH analogs with enhanced SSTR2 affinity might be useful in the medical therapy of PC, even when an OctreoScan is negative.

Adrenal Gland Neoplasms↗
PubMed2002

Somatostatin, but not somatostatin receptor subtypes 2 and 5 selective agonists, inhibits calcitonin secretion and gene expression in the human medullary thyroid carcinoma cell line, TT.

Somatostatin (SRIH) analogs are commonly used to treat symptoms in medullary thyroid carcinoma (MTC), that expresses SRIH receptors (SSTR1 to SSTR5), as does the human MTC cell line TT. The aim of this work was to evaluate whether SRIH, SSTR2 and SSTR5-selective agonists influence calcitonin (CT) secretion and gene expression in the TT cell line. CT secretion was evaluated by chemiluminescence, and gene expression was analyzed by Northern blot. TT cell line proliferation was also assessed by [(3)H] thymidine ([(3)H]thy) incorporation and viable cell number count. SRIH significantly (p < 0.05) reduced [(3)H]thy incorporation (approx. 50 %), viable cell number (approx. 20 %), CT secretion (-30 %) and CT gene expression (approx. 2-fold). Exposure to the SSTR2-selective agonist, BIM-23 120, and to the SSTR5-selective agonist, BIM-23 206, did not modify CT secretion and mRNA levels in TT cells. Thus, SRIH inhibits DNA synthesis, cell proliferation, CT secretion and CT gene expression in the TT cell line, while SSTR2 and 5 selective agonists, although influencing DNA synthesis and cell proliferation, do not modify CT gene expression, suggesting that SRIH may influence gene expression acting through SSTRs other than subtypes 2 and 5. Furthermore, these findings may explain the erratic response of MTC patients in terms of CT plasma levels to treatment with SRIH analogs, like octreotide and lanreotide, which interact mainly with SSTR2 and 5.

Blotting, Northern↗
PubMed2001

Pathogenesis and prevalence of hypertension in acromegaly.

Hypertension is an important complication of acromegaly, contributing to the increased morbidity and mortality of this condition. Prevalence of hypertension in acromegalic patients is about 35%, ranging from 18 to 60% in different clinical series, and the incidence is higher than in the general population. The lowering of blood pressure observed concomitantly with the reduction in GH levels after successful therapy for acromegaly suggests a relationship between GH and/or IGF-I excess and hypertension. The exact mechanisms underlying the development of hypertension in acromegaly are still not clear but may include several factors depending on the chronic exposure to GH and/or IGF-I excess. Experimental and clinical studies suggest that the anti-natriuretic action of GH (due to direct renal action of GH or IGF-I and/or to indirect, systemic GH or IGF-I-mediated mechanisms) may play a role in the pathogenesis of hypertension. Acromegaly is frequently associated with insulin resistance and hyperinsulinaemia which may induce hypertension by stimulating renal sodium absorption and sympathetic nervous activity. Whether sympathetic tone is altered in acromegalic hypertensive patients remains a matter of debate. Recent studies indicate that an increased sympathetic tone and/or abnormalities in the circadian activity of sympathetic system could play an important role in development and/or maintenance of elevated blood pressure in acromegaly, and may partially account for the increased risk of cardiovascular complications. Acromegalic cardiomiopathy may also concur to elevate blood pressure and can be aggravated by the coexistence of hypertension. Finally, a role of GH and IGF-I as vascular growth factors cannot be excluded. In conclusion, acromegaly is associated with hypertension, but there is still no real consensus in the literature on the mechanisms behind the development of the high blood pressure.

Acromegaly↗
PubMed2001

Blood growth hormone-binding protein levels in premenopausal and postmenopausal women: roles of body weight and estrogen levels.

A substantial proportion of GH circulates bound to high affinity GH-binding protein (GHBP), which corresponds to the extracellular domain of the GH receptor. Current evidence indicates that nutritional status has an important role in regulating plasma GHBP levels in humans. In the present study the relationship among plasma GHBP levels, body composition [by bioelectrical impedance analysis (BIA) and dual energy x-ray absorptiometry (DEXA)] and serum estradiol (E(2)) was evaluated in premenopausal (n = 92) and postmenopausal (n = 118) healthy women with different body weight [three groups according to body mass index (BMI): normal, 18.5-24.99; overweight, 25-29.99; obese, 30-39.99 kg/m(2)]. Plasma GHBP levels were measured by high pressure liquid chromatography gel filtration. GH and insulin-like growth factor I levels were determined by immunoradiometric assay and RIA, respectively. GHBP levels were significantly higher in premenopausal women with BMI above 25 kg/m(2) (overweight, 3.789 +/- 0.306 nmol/L; obese, 4.372 +/- 0.431 nmol/L) than those observed in postmenopausal women (overweight, 1.425 +/- 0.09 nmol/L; obese, 1.506 +/- 0.177 nmol/L). No significant differences were found between normal weight premenopausal (1.741 +/- 0.104 nmol/L) and postmenopausal (1.524 +/- 0.202 nmol/L) women. In premenopausal women GHBP levels correlated positively with BMI (r = 0.675; P < 0.001), fat mass (FM; r = 0.782; P < 0.001; by BIA; r = 0.776; P < 0.001; by DEXA), truncal fat (TF; r = 0.682; P < 0.001), waist to hip circumference ratio (WHR; r = 0.551; P < 0.001), and E(2) (r = 0.298; P < 0.05), whereas no significant correlation was found in postmenopausal women between GHBP levels and BMI, FM, TF, WHR, or E(2). In normal weight pre- and postmenopausal women GHBP levels did not change between the ages of 20 and 69 yr. No statistically significant correlation was found between GHBP and age for all groups studied. Moreover, in two distinct subgroups of pre- and postmenopausal women, aged 40-49 yr, the direct relationship between GHBP levels and all indexes of adiposity were only observed in premenopausal women [BMI: r = 0.836; P < 0.001; FM: r = 0.745 (BIA) and r = 0.832 (DEXA); P < 0.001; TF: r = 0.782; P < 0.001; WHR: r = 0.551; P < 0.05], but not in postmenopausal women. In conclusion, the present data indicate a strong direct correlation between GHBP and body fat in premenopausal, but not in postmenopausal women, whereas they failed to detect a relationship between GHBP and age. Therefore, these results suggest that endogenous estrogen status may be an important determinant of the changes in GHBP levels in women with different body weights.

Adult↗
PubMed2001

Somatostatin receptor subtypes 2 and 5 differentially affect proliferation in vitro of the human medullary thyroid carcinoma cell line tt.

Somatostatin and its receptors (SSTR1 to SSTR5) are expressed in normal human parafollicular C cells and medullary thyroid carcinoma (MTC), but the role of SSTR subtypes in cell growth regulation is still not clear. The present study demonstrates that the human MTC cell line TT stably expresses all the SSTR subtypes and responds to SSTR2 and SSTR5 activation by subtype-selective agonists with two different patterns in terms of [(3)H]thymidine ([(3)H]thy) incorporation and cell number. The SSTR2 preferential agonists (BIM-23120, BIM-23197, BIM-23190, and BIM-23014; 10(-9)-10(-6) M), significantly suppressed [(3)H]thy incorporation (58-13%) and reduced cell proliferation (50-28%), whereas the SSTR5-selective agonist, BIM-23206 (10(-9)-10(-6) M), significantly increased [(3)H]thy incorporation in TT cells (80-175%), but failed to influence cell proliferation. SSTR2 antagonist (BIM-23627) counteracted the action of SSTR2 preferential agonists on TT cells. Furthermore, increasing concentrations of SSTR5-selective agonists, BIM-23206, dose-dependently prevented the suppression of TT cell [(3)H]thy incorporation and proliferation produced by SSTR2 preferential agonist, BIM-23120, showing an antagonism between these compounds. The following conclusions were reached: 1) the human MTC cell line TT expresses all SSTR subtypes; 2) SSTR2 activation inhibits DNA synthesis and cell proliferation, whereas SSTR5 activation increases DNA synthesis; and 3) SSTR2 preferential agonist (BIM-23120) can antagonise SSTR5-selective agonist (BIM-23206) action and vice versa. These findings suggest a tissue-specific function and a tissue-specific interaction between the two receptors.

Carcinoma, Medullary↗
PubMed2001

Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone.

UNLABELLED: The use of recombinant human thyroid-stimulating hormone (rhTSH) has recently become available as an alternative diagnostic tool to assess the persistence and recurrence of differentiated thyroid carcinoma (DTC) in patients on thyroid hormone-suppressive therapy (THST) after near-total or total thyroidectomy and ablative doses of (131)I. We report the results of rhTSH administration in patients who were monitored for DTC. METHODS: Thirty-three adult DTC patients (13 men, 20 women; mean age +/- SE, 45.6 +/- 2.31 y; age range, 21-65 y) underwent diagnostic follow-up after rhTSH administration at a dose of 0.9 mg once a day for 2 d. Whole-body scanning and serum thyroglobulin (Tg) measurement were performed after rhTSH administration. Patients were divided into 2 groups depending on serum Tg concentrations on THST: 29 patients had Tg concentrations of <2 ng/mL (group A) and 4 patients had Tg values of >2 ng/mL (group B). RESULTS: In group A, Tg values remained at <2 ng/mL in 25 patients and increased from 1.1 +/- 0.14 ng/mL to 22.0 +/- 5.75 ng/mL (mean +/- SE) in 4 patients after rhTSH administration. Whole-body scanning did not reveal any uptake of (131)I in the 25 patients without an increase in Tg, whereas (131)I uptake was evident in 2 of the 4 patients with a rise in Tg. In group B, Tg values increased in all 4 patients from 17.3 +/- 6.35 ng/mL to 55.3 +/- 12.75 ng/mL, and (131)I uptake was evident in 3 of the 4 patients. No major adverse effects were reported after rhTSH administration. CONCLUSION: Our results show that the measurement of serum Tg concentrations after rhTSH has a higher diagnostic value than whole-body scanning in detecting the persistence of thyroid tissue. Therefore, rhTSH should be administered in TSH-suppressed patients with basal serum Tg concentrations of <2 ng/mL because the increment in serum Tg concentrations may reveal the persistence of thyroid tissue in these patients.

Adult↗
PubMed2000

Role of the serotonergic system in the genesis of vasovagal syncope.

AIMS: The hypotensive reflex responsible for vasovagal syncope appears related to a reduction in sympathetic neural outflow. Several animal studies suggest that serotonin may play a role in the genesis of this reflex, through inhibition of sympathetic activity. However, the role of the serotonergic system is unknown in humans. The purpose of the study was to investigate the role of the serotonergic system in the genesis of vasovagal syncope by means of the level of platelet and plasma serotonin, as well as plasma catecholamines, during tilt-induced syncope. METHODS AND RESULTS: Fifteen patients (age 34 +/- 16 years) with vasovagal syncope underwent a head-up tilt test (HUT, 60 degrees , 45 min). If syncope did not develop, 300 microg nitroglycerin was administered sublingually and patients continued to be tilted for a further 20 min. Blood samples were obtained in the supine position, and then after 3, 10, 15, 30, 45, 48 and 65 min of HUT. If syncope developed, blood samples were obtained at the beginning of the prodrome, during syncope and after the recovery of consciousness. Platelet and plasma serotonin and plasma catecholamines were measured using high-pressure liquid chromatography with electrochemical detection. Ten patients developed syncope during the unmedicated HUT and four after nitroglycerin. In these patients plasma adrenaline significantly increased from the last programmed sample before the prodrome to its beginning and showed a further increase during loss of consciousness, whereas plasma noradrenaline did not increase, as an expression of inhibition of sympathetic neural outflow. In the patients experiencing syncope, both platelet and plasma serotonin showed no significant change after tilt-up, at the beginning of prodrome, during syncope and after recovery of consciousness. CONCLUSION: These results do not suggest that the serotonergic system plays a role in the pathophysiology of vasovagal syncope.

Adolescent↗
PubMed2000

Androgen influences transforming growth factor-beta1 gene expression in human adrenocortical cells.

Sex steroid hormones have been shown to affect adrenocortical function and trophism, yet little is known about androgen action in human adrenocortical gland. In this study we examined the effects of androgens on transforming growth factor-beta1 (TGF/beta1) production by the human adrenocortical cell line, NCI-H295, which we recently demonstrated to express androgen receptor and whose growth is significantly reduced by dihydrotestosterone (DHT) treatment. TGFbeta1 is an important regulator of human adrenal development, with marked effects on steroid-producing cell function, and the production of distinct TGFbeta subtypes has been suggested to be regulated by steroid hormones in several tissues. To address potential TGFbeta1 induction by DHT, quantitative PCR and enzyme-linked immunoadsorbent assay were performed in NCI-H295 cells treated with DHT (from 10(-12)-10(-9) mol/L). DHT led to a significant dose-dependent increase in TGFbeta1 messenger ribonucleic acid expression and in biologically active TGFbeta1 protein levels in the conditioned media of NCI-H295 cells, demonstrating that androgen can induce TGFbeta1 expression and production. TGFbeta1 (10(-7)-10(-6) mol/L) was capable of significantly reducing cell proliferation (P < 0.05) after 24 h of treatment, as assessed by measuring [3H]thymidine incorporation in NCI-H295 cells. The addition of TGFbeta1-neutralizing antibody to cell cultures treated with different DHT concentrations (10(-9) and 10(-10) mol/L) blocked the inhibitory effect of TGF/beta1 on adrenocortical cell proliferation. These findings suggest that TGFbeta1 exerts an inhibitory action on adrenocortical cell proliferation. Therefore, it might be reasonable to suppose that DHT could also influence human adrenocortical cell growth by involving TGFbeta1.

Adrenal Cortex↗
PubMed1998

Effect of delta-opioid receptor agonist deltorphin on circulating concentrations of luteinizing hormone and follicle stimulating hormone in healthy fertile women.

There is evidence that endogenous opioid peptides exert an inhibitory effect on pituitary luteinizing hormone (LH) secretion both in animals and in humans, by interacting with mu-opioid receptors. However, a role for delta-opioid receptors in the regulation of gonadotrophin releasing hormone (GnRH) secretion has recently been suggested. In the present study, we evaluated the effect of the highly selective delta-opioid receptor agonist deltorphin on the LH and follicle stimulating hormone (FSH) responses to naloxone in six healthy fertile women during the luteal phase of the menstrual cycle. Deltorphin infusion alone (7 microg/kg/min for 60 min) did not significantly change the basal serum concentrations of LH in this group of women. The intravenous (i.v.) bolus administration of naloxone (15 mg) induced a significant (P < 0.001) increase in serum LH concentrations (from a mean basal value of 4.24+/-1.10 IU/l to a peak of 13.27+/-1.8 IU/l). The LH response to naloxone was significantly (P < 0.001) blunted by preinfusion of deltorphin (13.27+/- 1.80 IU/l versus 4.80+/-1.18 IU/l). No significant changes in FSH concentrations were observed during deltorphin, naloxone or deltorphin plus naloxone administration. These data indicate that activation of delta-opioid receptors can reduce naloxone-induced LH release, suggesting a possible role of delta receptors in opioidergic modulation of LH secretion in women.

Adult↗
PubMed1998

Unexpected activation of pituitary-adrenal axis in healthy young and elderly subjects during somatostatin infusion.

In this study we explored, in man, the effect of acute attenuation of growth hormone (GH) release induced by somatostatin (SRIH) on ACTH and cortisol plasma levels. Sixteen young (8 women, aged 23-32 years, and 8 men, aged 18-27 years) and 14 elderly (8 women, aged 65-82 years, and 6 men, aged 65-70 years) healthy subjects volunteered to participate in this investigation. Each subject was tested on two separate occasions by: (1) a 90-min i.v. infusion of SRIH given in 50 ml 0.9% saline delivered at a rate of 9 microg/kg/h, and (2) a 90-min i.v. infusion of isovolumetric amounts of 0.9% saline. Plasma GH, ACTH, cortisol and glucose concentrations were determined prior and up to 180 min after SRIH or saline infusion. SRIH induced a significant (p < 0.05) decrease in plasma GH levels from basal values of 0.6 +/- 0.15 and 0.5 +/- 0.15 microg/l to nadir values 0.25 +/- 0.1 and 0.2 +/- 0.1 microg/l in young and elderly subjects, respectively. The administration of SRIH was associated with a clear-cut increase in plasma ACTH levels both in young (peak, 10.6 +/- 1.6 pmol/l; AUC, 558.6 +/- 147.5 pmol/l/h) and in elderly (peak, 21.3 +/- 5.6 pmol/l; AUC, 841.9 +/- 153.8 pmol/l/h) subjects with a significant (p < 0.01) difference as compared to saline infusion. Consistent with these results, SRIH infusion resulted in an unequivocal rise in plasma cortisol levels both in young (peak, 394.8 +/- 36.4 nmol/l; AUC, 18,591.62 +/- 1,372.45 nmol/l/h) and in elderly (peak, 585.6 +/- 51.5 nmol/l; AUC, 24,871.05 +/- 1,837.03 nmol/l/h) subjects. The ACTH and cortisol responses to SRIH were significantly (p < 0.05 and p < 0.01) higher in elderly than in young subjects. No sex-related differences occurred in the SRIH-induced activation of hypothalamic-pituitary-adrenocortical (HPA) axis. We conclude that (1) infusion of SRIH, at a dose that inhibited basal GH secretion, was associated with an activation of HPA axis, and (2) this response was higher in elderly individuals compared with younger adults. The reason for this novel and unexpected SRIH effect is presently unclear; however, the latter may be mediated, at least in part, by some central nervous system ACTH-releasing mechanisms activated by SRIH-induced decrease in GH secretion.

Adolescent↗