Biomedical subjects

A Giustina

Publications and source records attributed to A Giustina.

At least 91 records · Page 5Linked to original sources

PubMed1995

Effect of glucocorticoids on the paradoxical growth hormone response to thyrotropin-releasing hormone in patients with acromegaly.

It has been hypothesized that in acromegalic patients, as well as in normal subjects, acute increases in serum cortisol levels may cause an enhancement of hypothalamic somatostatin secretion, which in turn may be responsible for the glucocorticoid-mediated growth hormone (GH) inhibition. The aim of this study was to investigate short-term effects of an intravenous (i.v.) infusion of hydrocortisone on the GH response to thyrotropin-releasing hormone (TRH) in acromegaly. We studied six adult patients with active acromegaly. The group was composed of four women and two men with a mean age of 55.8 +/- 6.4 years (range, 27 to 68) and a mean body mass index of 26.7 +/- 1 kg/m2 (range, 23.3 to 30). All patients underwent the following treatments: (1) hydrocortisone alone: a bolus i.v. injection of hydrocortisone succinate 100 mg in 2 mL saline at time -60 minutes, followed by a 120-minute i.v. infusion of hydrocortisone succinate 250 mg in 250 mL saline from -60 to 60 minutes; (2) TRH+hydrocortisone: a bolus i.v. injection of TRH 200 micrograms 60 minutes after initiation of a 2-hour hydrocortisone infusion; (3) TRH alone: a bolus i.v. injection of TRH at time 0, 60 minutes after initiation of a 2-hour saline infusion. In all six patients, TRH induced large GH increases (absolute peak GH level, 58.1 +/- 23.2 micrograms/L; maximum % GH change with respect to baseline, 1,397.8% +/- 807.8%; range, 205% +/- 5,219%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1995

Galanin counteracts the inhibitory effects of glucocorticoids on growth hormone secretion in the rat.

The aim of our study was to investigate the effect of galanin on baseline and growth hormone (GH)-releasing hormone (GHRH)-stimulated GH concentrations in conscious, freely moving rats receiving long-term glucocorticoid treatment. Animals were treated for 7 days with an intraperitoneal injection of either vehicle or dexamethasone ([dex] 40 micrograms/d). Rats underwent the following experimental trials: at -15 minutes animals received an intravenous injection of saline or galanin (12.5 micrograms/kg), and at 0 minutes rats received a second intravenous injection of saline or rat GHRH (500 ng/kg). Blood samples were drawn every 5 minutes from -15 to +15 minutes and then at 30 minutes. The GH response to saline + GHRH alone was significantly higher (P < .05) in chronically vehicle-treated rats as compared with chronically dex-treated ones. In contrast, galanin + saline increased serum GH levels in a similar fashion in both chronically vehicle- and dex-treated rats. The response to galanin + GHRH was similar to galanin + saline in chronically vehicle-treated rats, but was significantly enhanced in chronically dex-treated rats. These results suggest that galanin-mediated GH release in rats may involve somatostatinergic pathways.

Animals↗

PubMed1995

Hexarelin, a novel GHRP-6 analog, counteracts the inhibitory effect of hydrocortisone on growth hormone secretion in acromegaly.

Hexarelin (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a GHRP-6 analog with the substitution of D-tryptophan with its 2-methyl derivative. The aim of our study was to ascertain whether hexarelin was able to counteract the glucocorticoid-mediated increase in hypothalamic somatostatin tone and consequent inhibition on serum GH levels in acromegalic patients. Ten patients (5 males, 5 females; age range 27-71 years; BMI range 23.3-35 kg/m2) with active acromegaly underwent: 1) hydrocortisone alone: a bolus iv injection of 100 mg hydrocortisone succinate in 2 mL saline, at time -60 followed by a 120 min iv infusion of 250 mg hydrocortisone succinate in 250 mL saline, from -60 to 60 min; 2) hexarelin+hydrocortisone: a bolus iv injection of hexarelin 100 micrograms, 60 min after initiation of a 2-hour hydrocortisone infusion; 3) hexarelin alone: a bolus iv injection of hexarelin at time 0, 60 min after initiation of a 2-hour saline infusion. The mean GH peak, expressed as percent change with respect to baseline level (mean of -75 and -60 minute samples), after hexarelin (1750 +/- 1157%) did not differ significantly with respect to that observed after hexarelin+hydrocortisone (1120 +/- 770%). After hydrocortisone alone the patients showed a mean decrease in GH levels as compared to baseline levels, of 47 +/- 7%. Our data show that the GH response to hexarelin in acromegaly is resistant to the inhibitor action of an acute and sustained elevation of serum cortisol levels. That hexarelin counteracts the glucocorticoid-mediated inhibition of GH secretion supports the hypothesis of an hexarelin-induced decrease in endogenous somatostatin tone.

Acromegaly↗

PubMed1995

Adrenergic and cholinergic involvement in basal and growth hormone-releasing hormone-stimulated growth hormone secretion in glucocorticoid-treated rats.

Glucocorticoids are known to inhibit GH secretion via somatostatin. The aim of our study was to elucidate the involvement of somatostatin in the GH-releasing action of the alpha 2 agonist clonidine and the cholinergic agent pyridostigmine in conscious, freely-moving rats chronically treated with dexamethasone. After seven days of chronic glucocorticoid treatment, animals received an i.v. injection of either saline (1 ml/kg) or clonidine (150 micrograms/kg) or pyridostigmine (100 micrograms/kg) at -15 min. Three blood samples were then drawn (-10 min, -5 min, and 0 min) to assess the GH response to either clonidine or pyridostigmine alone. After the 0 min sample, saline (1 ml/kg) or GNRH (500 ng/kg) was injected i.v. and additional blood samples were drawn from 5 to 30 min. The GH response to clonidine alone or combined with GNRH in rats treated with dexamethasone was significantly lower (p < 0.05) as compared to vehicle-treated rats. The GH response to pyridostigmine alone or combined with GNRH did not significantly differ between vehicle- and dexamethasone-treated rats. These data suggest that in the rat the mechanism of action of clonidine is mainly to stimulate endogenous GNRH secretion, while pyridostigmine appears to predominantly act by decreasing hypothalamic somatostatin.

Adrenergic alpha-Agonists↗

PubMed1995

Mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH and somatostatin in the rat.

We have recently reported oral and parenteral bioactivity for a new GH-releasing peptide, hexarelin. In the present study, we have examined the neuroendocrine mechanism by which hexarelin and GHRP-6, two GH-releasing peptides, mediate their actions. Although previous studies have looked at the role of growth hormone-releasing hormone (GHRH) and somatostatin in regulating the action of GHRP-6 in culture and in stressed animals, our study looked at the role of both somatostatin and GHRH in regulating the action of hexarelin as well as GHRP-6 in conscious and freely-moving, nonstressed rats. Adult male rats, prepared with indwelling jugular catheters, were pretreated i.v. with either control antiserum (CTLas), growth hormone-releasing hormone antiserum (GHRHas), somatostatin antiserum (SSas), or both GHRHas and SSas. Animals were then treated i.v. with 25 micrograms/kg of either hexarelin or GHRP-6 4 h after i.v. antisera pretreatment. Blood samples were collected every 20 min for the 3 h prior to peptide treatment and at 5, 10, 15, 20, 40 and 60 min following hexarelin or GHRP-6 injection. The peak plasma GH responses in rats pretreated with CTLas were 552 +/- 125 ng/ml following hexarelin administration and 386 +/- 132 ng/ml following GHRP-6 administration. Rats pretreated with SSas exhibited peak GH responses following hexarelin or GHRP-6 of 702 +/- 115 and 312 +/- 42 ng/ml, respectively. These plasma GH responses were similar to those observed in the CTLas-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

Changes in the growth hormone axis due to exercise training in male and female rats: secretory and molecular responses.

GH secretion is altered by exercise in humans. In an attempt to investigate the underlying mechanisms, we developed a rodent model. GH secretion was assayed in male and female rats that were sedentary (not exercised), acutely exercised, and chronically exercised. Sedentary males showed typical pulsatile GH secretion. The acutely exercised males had low GH concentrations during the exercise bout, but showed partial recovery of GH pulses during the 5.5-h postexercise period. GH secretion in the chronically exercised males was low during both the exercise and postexercise periods. Sedentary females displayed the typical pattern of GH secretion for this sex. The acutely exercised females had low GH concentrations during the exercise period; the pulsatile pattern of GH secretion did not return during the postexercise period. In contrast, the chronically exercising females had suppressed GH secretion during the exercise bout, but concentrations immediately returned to normal during the postexercise bout. The effects of exercise on GH, GH-releasing hormone (GHRH), and somatostatin messenger RNA (mRNA) levels using Northern and slot blot analyses were also determined. Acutely and chronically exercised male rats had decreased levels of GH mRNA compared to sedentary male rats. The acutely exercised female rats had increased levels of GH mRNA compared to the sedentary females, whereas the chronically exercised females had decreased levels. GHRH mRNA levels in acutely exercising male rats was decreased and in chronically exercising male rats was increased compared to those in the sedentary controls. The pattern of GHRH mRNA in female rats was the opposite of this. Somatostatin mRNA levels decreased in acutely exercised male rats and were not affected in chronically exercised male rats. This signal increased in both acute and chronically exercised female rats. These studies suggest that GH secretion is suppressed in response to exercise in the rat. This contrasts with the increase observed after exercise in humans.

Animals↗

PubMed1995

Effects of recombinant human growth hormone (GH) on bone and intermediary metabolism in patients receiving chronic glucocorticoid treatment with suppressed endogenous GH response to GH-releasing hormone.

Glucocorticoids, when administered over prolonged periods of time, cause protein wasting, osteoporosis, elevation of total cholesterol, and carbohydrate intolerance. Human GH is a potent anabolic agent known to stimulate protein synthesis and osteoblast activity. Chronic hypercortisolemia is associated with impaired GH secretion. The aim of our study was to evaluate the effects of short term administration of human recombinant GH on bone and fuel metabolism in patients receiving chronic glucocorticoid treatment and with suppressed GHRH-stimulated GH peaks (< 10 micrograms/L). We studied nine nonobese adult patients more than 70 yr of age (seven females and two males; age range, 41-68 yr; body mass index, 26 +/- 1.3 kg/m2) undergoing long term glucocorticoid therapy for nonendocrine diseases. After a 3-day stabilization period in the hospital, several parameters were evaluated in all patients: 1) protein, 2) bone, 3) lipid, 4) carbohydrate metabolism, and 5) immune system function under baseline conditions. At 1800 h on the fifth day of hospitalization, the patients began treatment with a daily sc injection of 0.1 IU/kg (0.037 mg/kg) recombinant human GH (Humatrope, Eli Lilly Co.) for 7 days. GH administration caused a significant increase in nitrogen balance (from -0.12 +/- 0.04 to -0.03 +/- 0.02 g/kg.day; P < 0.05), osteocalcin, carboxy-terminal propeptide of type I procollagen, and carboxy-terminal telopeptide of type I collagen with respect to basal levels. After GH administration, total, high density lipoprotein, and low density lipoprotein cholesterol levels were significantly lowered, and serum triglyceride levels were increased in all patients. Normal blood glucose levels during GH administration were observed in our patients concomitantly with a slight increase in insulin secretion. After GH treatment, the T-helper/T-suppressor cell ratio significantly increased with respect to basal levels (2.5 +/- 0.4 vs. 2.2 +/- 0.3; P < 0.05). Our data suggest that in patients receiving chronic glucocorticoid treatment, GH administration may significantly antagonize several side-effects of long term glucocorticoid administration, such as protein wasting, osteoporosis, and hyperlipidemia.

Adult↗

PubMed1995

Characterization of the paradoxical growth hormone inhibitory effect of galanin in acromegaly.

Galanin is a 29-amino acid straight-chain biologically active peptide which has been found to decrease circulating GH levels in some acromegalic patients, whereas is able to increase GH secretion in normal subjects. The aim of our study was to ascertain the incidence, entity and mechanism of the paradoxical GH inhibitory effect of galanin in acromegaly also looking at possible correlations between the GH responses to galanin and the main clinical and biochemical features of the patients. Finally, the effects of either successful or unsuccessful neurosurgical intervention on the GH inhibitory effect of galanin in acromegaly were investigated. A series of 23 consecutive patients with active acromegaly seen at the Endocrine Section of the Department of Internal Medicine of the University of Brescia (Italy) between 1991 and 1994 was examined. The acromegalic patients were subdivided in group 1 (i.e. patients who were 1) untreated, 2) evaluated before surgery, and 3) not cured after surgery and radiotherapy) and group 2 (i.e. surgically cured). All patients were submitted at least once to the following biochemical and radiological evaluations: 1) baseline serum insulin-like growth factor-I and PRL samples, 2) iv infusion of synthetic porcine galanin (500 micrograms in 100 mL saline) from -10 to 30 min, 3) iv bolus injection of TRH (200 micrograms) at time zero, 4) oral glucose tolerance test (75 g glucose, orally) at time zero, and 5) magnetic resonance of the pituitary sella. Adenomatous tissue obtained during neurosurgery in four patients was cultured in vitro, and the effect of the addition of galanin in the culture medium on GH secretion was tested. During galanin infusion in 19 of 21 group 1 patients, serum GH levels were lower with respect to baseline (range of GH decrease, -6.2 to -85.4% with respect to basal levels). During galanin infusion, no reductions in GH levels were observed in the acromegalic patients cured after neurosurgery (group 2); on the contrary, 6 of 7 patients displayed a normal stimulatory response to galanin (range of GH increase, +120-1533.3% of the basal level). A significant correlation between the percent decrease in GH levels after galanin treatment and the percent increase after TRH was found in group 1 patients (r = -0.783; P < 0.05). In three of the four adenomas examined, galanin determined a clear decrease in GH secretion (mean nadir, 63.3 +/- 12% of the baseline secretion rate). In conclusion, we demonstrated that the large majority of numerous patients with active acromegaly show a decrease in serum GH levels after galanin administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗

PubMed1995

Influence of thyroid hormones on the regulation of growth hormone secretion.

The effects of thyroid hormones on GH secretion and the mechanisms underlying their action are very similar in man and the laboratory animal. We feel that it is possible to organize the available data into a unique pathophysiological model explaining these complex interactions (Table 1). In summary, physiological levels of circulating thyroid hormones are necessary to maintain normal pituitary GH secretion owing to their direct stimulatory actions. When the serum concentrations of thyroid hormone increase above the normal range there is an increase in hypothalamic somatostatin tone, which in turn suppresses pituitary GH secretion and overrides any stimulatory effects. The suppression of GH secretion by thyroid hormones may be mediated at the hypothalamic level also by a decrease in GHRH release.

Animals↗

PubMed1995

Comparison of the effects of growth hormone-releasing hormone and hexarelin, a novel growth hormone-releasing peptide-6 analog, on growth hormone secretion in humans with or without glucocorticoid excess.

The aim of our study was to investigate the effect of hexarelin, a novel GH-releasing peptide-6 analog, and GH-releasing hormone (GHRH) (alone or in combination) on GH secretion in adult patients with increased somatostatin tone due to chronic glucocorticoid excess. We studied seven adult patients undergoing long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for non-endocrine diseases (six females and one male, age range 42-68 years) and one subject (female, age 31 years) with endogenous hypercortisolism due to adrenal adenoma. Six normal subjects (four females and two males) matched for sex and age with the patients and not undergoing any therapy served as controls. All the subjects underwent the following three tests in random order: (1) human GHRH (1-29)NH2 (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min, (2) hexarelin (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min and (3) hexarelin (100 micrograms in 1 ml of saline) plus GHRH (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min. After GHRH alone the patients with glucocorticoid excess showed a blunted GH response as compared with normal subjects (median delta GH: 0.9, range 0-5.6 micrograms/l vs 7:1, range 0.3-14.9 micrograms/l). No significant differences were observed in the steroid-treated group with respect to normal subjects after hexarelin alone (median delta GH: 15.5, range 1.9-45.2 micrograms/l vs 17.9, range 5.5-53.9 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Cardiopulmonary adaptation to exercise after acute weight loss in severely obese subjects.

The aim of our study was to investigate the effects on baseline and exercise cardiopulmonary function and metabolic parameters of an acute (3-4 weeks) loss of at least 10% of initial weight in severely obese patients. Eight obese patients, 3 males and 5 females, mean age +/- SEM 42 +/- 6 yrs, body mass index (BMI) > 35 kg.m-2, underwent two cardiopulmonary function tests separated by 3 weeks of very low calorie protein-sparing diet (589 kcal.day-1) and a weight loss of 10% of initial weight (mean 8.43 +/- 0.72 kg). Eight normal subjects, matched for sex and age with the obese patients, served as controls. In the obese subjects, maximal workload (+15 +/- 3.6 W) and maximal oxygen consumption (V' O2) (+188 +/- 40.5 mL.min-1) were significantly increased after weight loss. Interestingly, exercise capacity at anaerobic threshold was not significantly different in obese subjects after weight loss with respect to normal subjects. Our results show that an acute but significant weight loss obtained with a very low calorie diet in obese patients is able to significantly improve maximal V' O2 and V' CO2 at anaerobic threshold. Moreover, this acute weight loss is able to partially reverse all of the cardiopulmonary alterations seen in obese patients both at baseline and during exercise.

Adaptation, Physiological↗

PubMed1994

Inhibitory effect of galanin on growth hormone release from rat pituitary tumor cells (GH1) in culture.

The growth hormone (GH) releasing effect of GH-releasing hormone (GHRH) and galanin, a 29-amino acid peptide widely distributed in mammalian CNS, was investigated in cultured rat pituitary tumor cells (GH1) as compared to normal rat somatotrophs. GHRH stimulated dose-dependently GH secretion in normal somatotrophs but did not affect GH secretion in GH1 cells. Galanin (1-10 microM) stimulated GH release in a concentration-dependent manner, but with lower potency as compared to GHRH, in normal rat pituitaries but was inhibitory in rat GH1 cells. The results of this study indicate that while galanin has the ability to stimulate GH release from dispersed pituitary cells of normal rats it has potent direct inhibitory effects on GH release from tumor rat cells.

Animals↗

PubMed1994

Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II Diabetic patients.

A suppressed growth hormone (GH) response to GH-releasing hormone (GHRH) in both lean and overweight type II diabetics has been reported. Pyridostigmine (PD), an acetylcholinesterase inhibitor, elicits GH secretion when administered alone and enhances the GH response to GHRH in normal subjects. The aim of our study was to evaluate the effect of PD on GHRH-stimulated GH secretion in both lean and obese type II diabetic patients. We studied 16 patients with type II diabetes mellitus (seven lean and nine obese). Eleven nondiabetic subjects (six lean and five obese) served as controls. Each subjects underwent treatment with (1) 120 mg PD orally or (2) 2 tablets of placebo orally, 60 minutes before intravenous (IV) injection of 100 micrograms GHRH-(1-29)NH2. We have found no significant differences in GH responses to GHRH between obese diabetics and obese controls. On the other hand, the absolute GH levels were significantly suppressed in lean type II diabetics compared with lean controls at 15 and 30 minutes after GHRH injection. Obese diabetic subjects had slightly but not significantly decreased GH responses to GHRH+PD compared with obese nondiabetic subjects (8.36 +/- 1.62 v 14.4 +/- 7.62 micrograms/L). Lean type II diabetics showed a blunted GH release after GHRH+PD compared with normal-weight healthy subjects (GH peaks, 15.77 +/- 2.17 v 40.88 +/- 6.17 micrograms/L, P < .05). PD enhanced significantly the GH response to GHRH in obese diabetics, obese controls, and non-obese controls (P < .05), but not in non-obese type II diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1994

Effect of pyridostigmine on the hydrocortisone-mediated decrease of circulating growth hormone levels in acromegaly.

The aims of our study were to investigate the effect of the acetylcholinesterase inhibitor pyridostigmine (PD) administration on growth hormone (GH) secretion in acromegaly and to investigate the effects of PD on GH levels following an i.v. infusion of hydrocortisone in acromegaly. We studied five adult patients with active acromegaly, three men and two women with a mean age of 60 +/- 5 years (range 47-71 years) and a mean BMI of 27 +/- 0.7 kg/m2 (range 24-28 kg/m2). All the patients underwent: 1) placebo, 2 tablets po or 2) PD, 120 mg po, at time -60 plus a bolus i.v. injection of 100 mg hydrocortisone succinate in 2 ml saline at time 0 followed by an i.v. infusion of 250 mg hydrocortisone succinate in 250 ml saline from 0 to 120 min, or 3) PD, po or 4) placebo, po at time -60 plus a bolus i.v. injection of 2 ml saline followed by an i.v. infusion of 250 ml saline from 0 to 120 min. Serum GH values did not significantly change after PD administration compared to those during placebo treatment and with respect to baseline levels. In all of the acromegalic patients during hydrocortisone succinate infusion, GH values clearly decreased with respect to basal levels in varying degrees, with a nadir between 90 and 180 minutes after the beginning of hydrocortisone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1994

Physiological role of galanin in the regulation of anterior pituitary function in humans.

The aim of our study was to elucidate the physiological role of the neuropeptide galanin in the regulation of anterior pituitary function in human subjects. Six healthy men (age range 26-35 yr, body mass index range 20-24 kg/m2) underwent in random order 1) an intravenous bolus injection of growth hormone-releasing hormone (GHRH)-(1-29)-NH2 (100 micrograms) + thyrotropin-releasing hormone (TRH, 200 micrograms) + luteinizing hormone-releasing hormone (LHRH, 100 micrograms) + corticotropin-releasing hormone (CRH, 100 micrograms), and 2) intravenous saline (100 ml) at time 0 plus either human galanin (500 micrograms) in saline (100 ml) or saline (100 ml) from -15 to +30 min. Human galanin determined a significant increase in serum GH (GH peak: 11.3 +/- 2.2 micrograms/l) from both baseline and placebo levels. No significant differences were observed between GH values after galanin and those after GHRH alone (24.3 +/- 5.2 micrograms/l). Human galanin significantly enhanced the GH response to GHRH (peak 49.5 +/- 10 micrograms/l) with respect to either GHRH or galanin alone. Human galanin caused a slight decrease in baseline serum adrenocorticotropic hormone (ACTH; 16.3 +/- 2.4 pg/ml) and cortisol levels (8 +/- 1.5 micrograms/dl). Galanin also determined a slight reduction in both the ACTH (peak 27 +/- 8 pg/ml) and cortisol (peak 13.8 +/- 1.3 micrograms/dl) responses to CRH. Baseline and releasing hormone-stimulated secretions of prolactin, thyroid-stimulating hormone, LH, and follicle-stimulating hormone were not altered by galanin. Our data suggest a physiological role for the neuropeptide galanin in the regulation of GH secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1994

Effect of hydrocortisone on the growth hormone response to growth hormone-releasing hormone in acromegaly.

Our recent data show that acute and sustained hypercortisolism decreases circulating growth hormone (GH) levels in acromegaly with respect to saline infusion. It has been hypothesized that in acromegalic patients, as well as in normal subjects, short-term increases in serum cortisol levels may be able to cause an enhancement of hypothalamic somatostatin secretion, which in turn may be responsible for the glucocorticoid mediated GH inhibition. The aim of our study was to investigate the acute effects of an intravenous infusion of hydrocortisone on the GH response to growth hormone-releasing hormone (GHRH) in acromegaly. We studied 6 adult patients with active acromegaly (3 M, 3 F; mean age 60.5 +/- 4.1 years; mean body mass index 27.1 +/- 0.6 kg/m2). All the patients underwent: (1) a bolus intravenous injection of 100 mg hydrocortisone succinate in 2 ml saline, at time -60 followed by a 120-min intravenous infusion of 250 mg hydrocortisone succinate in 250 ml saline, from -60 to 60 min; (2) a bolus intravenous injection of human GHRH 1-29NH2 100 micrograms in 1 ml saline, 60 min after initiation of a 2-hour hydrocortisone infusion; (3) a bolus intravenous GHRH injection 60 min after initiation of a 2-hour saline infusion. In all of the acromegalic patients during hydrocortisone succinate infusion, GH values clearly decreased with respect to basal levels (mean nadir 47 +/- 8.6%, p < 0.05 with respect to basal levels). After GHRH injection and saline infusion all the patients showed a significant increase in GH levels (mean peak 231.5 +/- 52.8%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1994

Reciprocal relationship between the level of circulating cortisol and growth hormone secretion in response to growth hormone-releasing hormone in man: studies in patients with adrenal insufficiency.

The aim of our study was to elucidate the relationship between the level of circulating cortisol and the GH responsiveness to GHRH in six hypoadrenal patients (one male and five females; age range, 35-67 yr; body mass index range, 18-31 kg/m2). Twenty-four hours after taking the last dose of replacement therapy, each patient underwent the following experimental trials on nonconsecutive days: 1) saline, and 2) 12.5 mg, or 3) 25 mg, or 4) 250 mg hydrocortisone hemisuccinate in 250 mL saline constant iv infusion from 0-180 min. On each occasion, 1 micrograms/kg human GHRH-(1-29)NH2 was injected as an iv bolus at 60 min. During GHRH and saline infusion, serum cortisol levels were always less than the detection limit of the assay (55 nmol/L). During 12.5-, 25-, and 250-mg hydrocortisone infusions (from 15-180 min), serum cortisol averaged 413.8 +/- 19.3, 772.5 +/- 46.9, and 1520.2 +/- 110.4 nmol/L, respectively. The GH peaks after GHRH treatment during the various infusions of hydrocortisone were compared to the GH peaks observed after saline, which were normalized to 100% in each subject. GH peaks after GHRH and 25 mg hydrocortisone (70 +/- 11%) and GHRH and 250 mg hydrocortisone (69 +/- 7%) were significantly (P < 0.05) lower than the GH peaks after GHRH and saline or GHRH and 12.5 mg hydrocortisone (83 +/- 15%). No significant differences were observed between the GH peaks after GHRH and 12.5 mg hydrocortisone or GHRH and saline. Our data demonstrate that in hypoadrenal patients, the acute absence of circulating cortisol does not impair the GH secretory response to GHRH with respect to the eucortisolemic state. Moreover, our data suggest that 700 nmol/L is the approximate threshold serum cortisol concentration above which a decrease in the GH responsiveness to GHRH is observed in humans. Further increases in serum cortisol levels above this threshold value do not cause a proportional decrease in the GH responsiveness to GHRH.

Addison Disease↗

PubMed1994

Effect of the combined administration of galanin and clonidine on serum growth hormone levels in normal subjects and in patients under chronic glucocorticoid treatment.

Aim of our study was to investigate the effect of clonidine and galanin (alone or in combination) on growth hormone (GH) secretion in normal subjects and in adult patients with increased somatostatin tone due to chronic daily immunosuppressive glucocorticoid treatment. We studied 7 adult patients undergoing long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for non endocrine diseases (4F, 3M; age 49.7 +/- 6.3 years). Six normal adult nonobese subjects (3F, 3M; age 34 +/- 2.7 years) served as controls. All subjects underwent the following three tests in random order: 1) iv infusion of clonidine, 150 micrograms in 10 mL of saline, from time 0 to 10 min; 2) iv infusion of synthetic porcine galanin, 500 micrograms in 100 mL of saline from -15 to 30 min; 3) iv infusion of clonidine from 0 to 10 min combined with synthetic porcine galanin iv infusion from -15 to 30 min. Blood samples for GH assay were taken at -15, 0, 15, 30, 45, 60, 90, 120 min. No significant differences in GH absolute values were observed at any time between the three different tests within each group of subjects. Normal subjects showed significantly (p < 0.05) higher GH peaks and GH absolute values from 15 to 90 min after galanin alone, clonidine alone and clonidine+galanin with respect to the glucocorticoid-treated patients. The absence of any either synergistic or at least additive effect on GH secretion of galanin and clonidine in conditions of both normal and increased somatostatin tone suggests that also in man, as well as in the rat, the action of galanin on the GH axis may be mediated through alpha-adrenergic pathways.

Adult↗