Biomedical subjects

W B Wehrenberg

Publications and source records attributed to W B Wehrenberg.

At least 19 recordsLinked to original sources

PubMed1995

Effect of GHRP-6 and GHRH on GH secretion in rats following chronic glucocorticoid treatment.

The aim of our study was to investigate the effects of His-DTrp-Ala-Trp-Phe-Lys-NH2 (GHRP-6) on baseline and growth hormone-releasing hormone (GHRH) stimulated growth hormone (GH) release in conscious, freely-moving rats receiving chronic glucocorticoid treatment. Animals were treated daily for seven days with either vehicle or dexamethasone (dex, 40 micrograms/day). On the day of experimentation, rats received an i.v. injection of saline or GHRP-6 followed 15 min later by an i.v. injection of saline or rat GHRH. Three doses of GHRP-6 were evaluated, 1 microgram, 4 micrograms and 25 micrograms/kg; one dose of GHRH was evaluated, 500 ng/kg. GHRP-6 increased plasma GH levels over baseline concentrations in a dose-dependent fashion both in vehicle- and dex-treated rats. The GH response to GHRP-6 and GHRH was significantly less in dex-treated rats as compared to vehicle-treated rats. The combined administration of GHRP-6 and GHRH did not result in any change in plasma GH levels which could not be predicted from the administration of either peptide alone. Our results show that GHRP-6 is able to stimulate GH secretion in glucocorticoid-treated rats but it is unable to counteract the glucocorticoid-induced inhibition of GH secretion.

Amino Acid Sequence↗

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

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

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↗

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

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

Growth hormone-releasing hexapeptide is a potent stimulator of growth hormone gene expression and release in the growth hormone-releasing hormone-deprived infant rat.

The growth hormone-releasing hexapeptide (GHRP-6) specifically stimulates growth hormone (GH) secretion in several animal species and humans. The mechanism of action of GHRP-6 is largely unknown, although experimental evidence indicates that it may modulate growth hormone-releasing hormone (GHRH) and somatostatin actions at the pituitary or hypothalamic level. To gain more insight into the mechanism(s) of action of GHRP-6, we studied the infant rat, an animal model highly responsive to GH-releasing stimuli. In 14-d-old rats GHRP-6 (32-600 micrograms/kg, s.c.) induced a marked and dose-dependent rise in plasma GH concentrations, maximal stimulation occurring with the dose of 300 micrograms/kg. Neither GHRH nor somatostatin antiserum prevented or modified the GH release elicited by GHRP-6. In pups passively immunized with GHRH antibodies, a 5-d treatment with GHRP-6 (80 micrograms/kg, s.c., twice daily) completely counteracted the inhibitory effect of GHRH deprivation on GH mRNA expression. In vitro GHRP-6 (10(-7) and 10(-6) M) induced a small and transient stimulation of GH release from cultured pituitary cells. These results indicate the following: 1) GHRP-6 is a potent stimulator of GH release in rat pups; 2) it stimulates GH gene expression in the GHRH-deprived pup; 3) during the neonatal period its action is not mediated by GHRH or somatostatin; and 4) its actions are not directed at the somatotrophs.

Animals↗

PubMed1994

Somatotropic dysfunction in growth hormone-releasing hormone-deprived neonatal rats: effect of growth hormone replacement therapy.

In a previous work, we reported that passive immunization with anti-growth hormone-releasing hormone (GHRH) antibodies (GHRH-Ab) in neonatal rats caused disruption of somatotropic function that was still present 60 d posttreatment. We studied the reversibility of this condition by growth hormone (GH) replacement therapy. Neonatal rats received GHRH-Ab (50 microL/rat, s.c.) or normal rabbit serum every second day from birth up to postnatal d 10 and received hGH (0.4 microgram/g body weight, s.c., b.i.d.) or vehicle in a 2 x 2 factorial design. Animals were studied on d 11 of age. In GHRH-Ab-treated rats, GH therapy 1) counteracted the reduced body weight and low plasma IGF-I levels; 2) failed to modify the reduced pituitary weight and GH content; 3) further reduced the low plasma GH levels; 4) partially restored the defective GH responsiveness to GHRH; 5) failed to modify the reduced hypothalamic somatostatin and increased GHRH gene expression in the hypothalamus; and 6) reverted the decreased pituitary somatostatin binding. Morphologic and morphometric evaluation of the pituitary gland from GHRH-AB+GH pups showed that the number of GH-labeled structures was lower than in normal rat serum-GH-treated pups, whereas the total GH immunoreactivity per unit surface, an index of intracellular hormone concentration, was slightly higher than in vehicle-GH or GHRH-Ab pups. As determined by electron microscopy, somatotropes from GHRH-Ab+GH pups had morphologic features of high cellular activity. It appears that in GHRH-deprived pups GH replacement therapy can normalize most but not all altered indices of the somatotropic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Growth hormone (GH) deprivation induced by passive immunization against rat GH-releasing factor does not disturb the course of sexual maturation and fertility in the female rat.

The importance of normal GH secretion for the onset of sexual maturation is a subject of controversy. Also, the need to achieve a minimal body size or body fat content has been postulated to be of importance for determining the timing of the onset of puberty. To evaluate the importance of GH secretion on the onset of sexual maturation in the female rat, GH deprivation has been induced by treating prepubertal rats with antirat GRF serum to passively immunize these animals against GRF. Chronic administration of anti-GRF serum produced in all series an impressive reduction in growth rate (from 5 to 2 g/day), resulting in a body weight averaging 50-60% the normal value at 50 days of life. Despite this deficit in growth, sexual maturation, as established by vaginal opening and first estrous cycles, occurred at the normal age in three of four series of rats; in one series, however, sexual maturation was delayed by 4 days, but thereafter, all parameters indicated that the gonadotropic axis was normally activated. In one series, fertility was tested at 59 days of age in females with a body weight corresponding to 51% of the control weight; these females conceived and delivered a reduced number of pups (9.4 +/- 0.7 instead of 14.2 +/- 0.8 in control dams), but the pups were of normal size. In a second experimental approach, the effect of GH deprivation was evaluated in a model of late sexual maturation obtained by severe food restriction followed by a switch to ad libitum feeding. Severe food restriction initiated at approximately 28 days, when the body weight was 75 g, drastically reduced the growth rate and completely prevented sexual maturation. A switch to ad libitum feeding at 50 days provoked an important compensatory growth and the occurrence of sexual maturation 4 days later. Passive immunization against GRF during this recovery phase did reduce the growth rate, but did not delay sexual maturation. Plasma insulin-like growth factor-I (IGF-I) secretion was very low in food-restricted rats and in each situation with induced GH deprivation. During food restriction, plasma IGF-binding protein-3 (IGFBP-3) and to a lesser extent IGFBP-1 were decreased, and IGFBP-2 was increased; after switching to ad libitum feeding, plasma levels of IGFBP-2 normalized, but levels of IGFBP-1 and IGFBP-3 remained low in the face of normalized plasma IGF-I levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

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

Long-term changes of somatotrophic function induced by deprivation of growth hormone-releasing hormone during the fetal life of the rat.

We have studied the effects of intra-amniotic administration of an anti-GH-releasing hormone serum (GHRH-Ab) on day 16 of fetal life in the rat, when the ontogenetic development of the GHRH neuronal system occurs. Control animals received normal rabbit serum. Following delivery, body weight was monitored for the next 30 days as an index of somatic growth, and the following indices of somatotrophic function were determined: plasma and pituitary GH, pituitary GH mRNA, hypothalamic GHRH and somatostatin mRNA, and the in vivo GH responsiveness to GHRH. At birth, GHRH-Ab-treated rats had a body weight that was equivalent to that of control rats but, starting from postnatal day 6 up to day 30, they had a significantly reduced body weight. Pituitary weight, the absolute pituitary GH content and GH mRNA levels were lower in experimental compared with control rats, while pituitary GH concentrations were similar in the two groups, thus implying that there was a defect, not only in GH synthesis, but also in GH release. In agreement with this theory, basal GH levels and GHRH-stimulated GH secretion were reduced in GHRH-Ab-treated rats but, in contrast, hypothalamic regulation of GH secretion appeared to be working in these rats as they were still able to respond to the low plasma GH by increasing GHRH and decreasing somatostatin mRNA levels. These findings indicate that deprivation of GHRH during fetal life induces long-lasting changes of growth rate and somatotrophic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗

PubMed1993

Variability in the growth hormone response to growth hormone-releasing hormone alone or combined with pyridostigmine in type 1 diabetic patients.

In man the GH response to GHRH is variable within and between subjects. Pyridostigmine (PD), an acetylcholinesterase inhibitor, has been shown to reduce the variability of the GH response to GHRH in normal subjects. The aim of this study was to assess the existence of either inter- or intraindividual variability in the GH response to GHRH in type 1 diabetic patients. Moreover, we investigated the effect of PD on such variability in the same patients. Seven (4 females-3 males) nonobese type 1 diabetic patients underwent two experiments performed in consecutive days according to a single-blind protocol: 1) 120 mg oral PD 60 min before iv injection of human (h) GHRH-(1-29) NH2, 100 micrograms in 2 ml of sterile water; 2) oral placebo 60 min before iv injection of 100 micrograms hGHRH. The two experiments were then repeated, following the same procedure, one and two weeks after the start of the study. The GH peaks after GHRH were variable within different subjects but also in the same subject on different occasions. However, the mean GH peak levels after GHRH in the three tests were not significantly different (14.2 +/- 3.5, 15.3 +/- 3, 16.5 +/- 6.4 micrograms/L, respectively), the coefficient of variation for each test was 65%, 51.8%, 102.4%, respectively (mean 73.1 +/- 15.1%). The GH response to GHRH was always significantly enhanced by PD administration: the mean GH peak levels in the three tests were 31.9 +/- 7.1, 44.8 +/- 10.4, 49.9 +/- 13.1 micrograms/L, respectively, without significant differences between tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Hypothalamic regulation of growth hormone secretion during food deprivation in the rat.

Suppressed pulsatile GH secretion in food-deprived rats has been hypothesized to be due to an increase in hypothalamic somatostatin secretion. We investigated this hypothesis and the role of GHRH in regulating GH secretion during food deprivation using two different models. In experiment one, rats were food deprived for 72h during which time they received a saline infusion (n = 5). At the same time rats were normal fed for 72h during which time they received a somatostatin infusion (5 micrograms/h, n = 7). After the 72h infusion period, all rats received two iv injections of GHRH (1 microgram/rat) at 2h intervals. GH concentrations in food-deprived rats rose from approximately 10 ng/ml to 400-800 ng/ml in response to both GHRH injections. This increase was significantly greater (p < 0.01) than the GH response (100-400 ng/ml) observed in somatostatin-infused animals. The significantly higher GH response observed in food-deprived rats as compared to somatostatin-infused, normal-fed rats suggests that somatostatin concentrations may decrease during food deprivation. In experiment two, rats were infused for 5h with either saline (n = 6) or GHRH (10 micrograms/h, n = 9) at the end of a 72h fast. GH concentrations did not change in saline-infused animals. In contrast, GH concentrations significantly increased (p < 0.01) upon initiation of the continuous GHRH infusion. Yet, this release of GH was pulsatile in nature. Pulsatile GH secretion in the presence of a constant GHRH infusion suggests that pulsatile somatostatin release from the hypothalamus is maintained during food deprivation. These studies suggest that during food deprivation in the rat 1) absolute concentrations of somatostatin decrease, but its pattern of secretion remains pulsatile, and 2) decreased GHRH release may be responsible for the absence of spontaneous GH pulses.

Animals↗

PubMed1993

Effects of metoclopramide on the growth hormone response to galanin in normal man.

One of the most prominent metabolic effects of the systemic administration of the synthetic neuropeptide galanin in man is the increase in growth hormone (GH) secretion. This stimulating action of galanin is thought to occur directly at the hypothalamic level through the release of GHRH. Recently, it has been shown that also dopaminergic drugs may elicit GH secretion through an increase in hypothalamic GHRH secretion. The aim of this study was to investigate if the action of galanin on GHRH and consequently on GH release may be mediated via dopaminergic pathways evaluating the effects of a potent central dopaminergic receptor blocker, metoclopramide (MCP), on the galanin-induced growth hormone (GH) secretion in normal subjects. We studied seven young non obese healthy subjects (three females and four males). GH secretion was evaluated after 45 min iv infusion of porcine galanin (0.5 mg in 100 ml of saline) from 0 to 45 min combined with a 60 min iv infusion of a) saline (100 ml) or b) MCP (10 mg in 100 ml of saline) from -15 to 45 min. In all the seven subjects, during galanin infusion, GH values increased with respect to baseline with peaks occurring between 30 and 60 min after the beginning of galanin infusion. Peak GH values ranged between 3.5 and 15.4 micrograms/l (mean 10.4 +/- 1.6 micrograms/l). During MCP infusion no significant differences in the GH response to galanin with respect to saline were observed both when absolute GH levels and GH AUC were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Effect of galanin on the growth hormone (GH) response to GH-releasing hormone in patients with Cushing's disease.

Attenuated plasma GH secretion during sleep and blunted GH responses to provocative stimuli have been observed in patients with Cushing's disease. Synthetic porcine galanin elicits GH secretion when given alone, and enhances the GH response to GHRH in normal human subjects. The aim of our study was to investigate the effects of galanin on the GH response to GHRH in patients with Cushing's disease. We studied 5 female subjects with untreated active Cushing's disease caused by micro-pituitary adenomas (age 43 +/- 6.7 years; BMI 30 +/- 0.7 kg/m2). Four normal adult females, matched for age and body weight with the patients with Cushing's disease, were studied as controls. Subjects underwent in random order: (1) infusion of synthetic porcine galanin IV, 500 micrograms in 100 mL; (2) infusion of saline, IV, 100 mL. A bolus of human GHRH(1-29)NH2 (Geref, Serono, Italy), 100 micrograms in 1 mL saline, was injected IV at 0 minutes. Patients with Cushing's disease showed blunted GH peaks after GHRH (1.2 +/- 0.4 micrograms/L) during saline infusion, as compared to normal controls (24.6 +/- 4.6 micrograms/L; p < 0.05). During galanin infusion a significantly enhanced GH response to GHRH, as compared with saline infusion, was observed in control subjects (GH peak: 51.4 +/- 9.8 micrograms/L; p < 0.05), but not in patients with Cushing's disease (GH peak: 2.3 +/- 0.6 micrograms/L). GH levels were significantly lower both after saline and after galanin in patients with Cushing's disease as compared to normal controls. Our data demonstrate that galanin is not able to enhance the GH response to GHRH in patients with Cushing's disease. That galanin cannot reverse this effect suggests that the mechanism of action of galanin is not via a decrease in somatostatin release by the hypothalamus.

Adenoma↗