Effects of repetitive administration of thyrotropin-releasing hormone at short intervals in acromegaly

1989 ◽  
Vol 120 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Marco Losa ◽  
Julia Alba-Roth ◽  
Sylwester Sobieszczyk ◽  
Jochen Schopohl ◽  
O. Albrecht Müller ◽  
...  
Keyword(s):  
Qualitative Difference ◽  
Area Under The Curve ◽  
Normal Subjects ◽  
Short Intervals ◽  
Repeated Stimulation ◽  
Gh Secretion ◽  
The Third ◽  
Tsh Secretion ◽  
Kinetics Of ◽  
Serum Gh

Abstract. We investigated the pattern of GH secretion in response to repetitive TRH administration in patients with active acromegaly and in normal subjects. Nine acromegalic patients and 10 normal subjects received three doses of 200 μg of TRH iv at 90-min intervals. There was a marked serum GH rise in acromegalic patients after each TRH dose (net incremental area under the curve [nAUC]: first dose = 4448 ± 1635 μg · min · 1−1; second dose = 3647 ± 1645 μg · min · 1−1; third dose = 4497 ± 2416 μg · min · 1−1; NS), though individual GH responses were very variable. In normal subjects TRH did not elicit GH secretion even after repeated stimulation. Each TRH administration stimulated PRL release in acromegalic patients, though the nAUC of PRL was significantly higher after the first (1260 ± 249 μg · min · 1−1) than after the second and the third TRH administration (478 ± 195 and 615 ± 117 μg · min · 1−1, respectively; P < 0.01). In normal subjects too, PRL secretion was lower after repeated stimulation (first dose = 1712 ± 438 μg · min · 1−1; second dose = 797 ± 177 μg · min · 1−1; third dose = 903 ± 229 μg · min · 1−1 P < 0.01), though different kinetics of PRL secretion were evident, when compared with acromegalic patients. TSH secretion, assessed in only 4 patients, was stimulated after each TRH dose, though a minimal but significant reduction of nAUC of TSH after repeated TRH challenge occurred. Both T3 and T4 increased steadily in the 4 patients. The same pattern of TSH, T3, and T4 secretion occurred in normal subjects. Our study demonstrates that repetitive TRH administration in acromegalic patients leads to similar, but individually heterogeneous GH responses. A qualitative difference in PRL responsiveness occurred in acromegalic patients compared with normal subjects, whereas TSH, T3, and T4 secretion was qualitatively and quantitatively similar in both groups.

scholarly journals Somatotropic responses to soy protein alone and as part of a meal.

2008 ◽  
Vol 159 (1) ◽  
pp. 15-18 ◽  
Author(s):  
Anneke J A H van Vught ◽  
Arie G Nieuwenhuizen ◽  
Robert-Jan M Brummer ◽  
Margriet S Westerterp-Plantenga
Keyword(s):  
Soy Protein ◽  
Dietary Fat ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Dietary Carbohydrates ◽  
Oral Ingestion ◽  
Gh Secretion ◽  
Important Regulator ◽  
Insulin Responses ◽  
Serum Gh

ContextGH is an important regulator of growth and body composition. We previously showed that GH release can be promoted by oral ingestion of soy protein; it is not known, however, whether these somatotropic effects of soy protein are also present when soy protein is ingested as part of a complete meal.Objective/designWe compared the effects of oral ingestion of soy protein alone with the effects of a meal containing the same amount of soy protein on GH secretion in six healthy women (body mass index 19–26 kg/m2, 19–36 years), in a randomized crossover design. During the whole experiment, serum GH, insulin, and glucose were determined every 20 min.ResultsGH responses as determined by area under the curve (AUC) and peak values were lower after ingestion of the meal, in comparison with GH responses after the soy protein consumption alone (P<0.05), and did not differ from the placebo. Glucose and insulin responses, both determined as AUC and peak values, were higher after ingestion of the meal, compared with those after ingestion of the protein drink or the placebo (P<0.05).ConclusionThe somatotropic effect of soy protein is reduced and delayed when soy protein is ingested as part of a complete meal. Dietary carbohydrates, by increasing serum levels of glucose and insulin concentration, as well as dietary fat, may have interfered with the somatotropic effects of soy protein.

Inhibition of foetal growth hormone (GH) and thyrotrophin (TSH) secretion after maternal administration of somatostatin

1984 ◽  
Vol 106 (3) ◽  
pp. 393-399 ◽  
Author(s):  
Elio Roti ◽  
Giuseppe Robuschi ◽  
Alessandro Alboni ◽  
Rossella Emanuele ◽  
Lorenzo d' Amato ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cord Blood ◽  
Pregnant Women ◽  
Marked Decrease ◽  
Maternal Blood ◽  
Gh Secretion ◽  
Foetal Growth ◽  
Tsh Secretion ◽  
Maternal Administration ◽  
Serum Gh

Abstract. Somatostatin (SRIF) was infused (500 μg over 30 min) into 68 pregnant women during labour. As a control, saline was infused into 26 pregnant women. Maternal blood was obtained prior to the infusion and at delivery and cord blood was obtained at delivery. The subjects were divided into 4 groups based upon the interval of time from the termination of SRIF infusion and delivery. There was a marked decrease in cord blood thyrotrophin (TSH) from 0 to 180 min and in cord blood growth hormone (GH) from 0 to 120 min following SRIF infusion. SRIF infusion did not affect cord blood iodothyronine and thyroglobulin concentrations. SRIF administration induced a small but significant (P < 0.05) decrease in serum GH concentration but had no other effect on maternal hormone values. These studies strongly suggest that SRIF crosses the human placenta and transiently suppresses foetal anterior pituitary TSH and GH secretion.

scholarly journals Effects of gender on exercise-induced growth hormone release

1999 ◽  
Vol 87 (3) ◽  
pp. 1154-1162 ◽  
Author(s):  
Laurie Wideman ◽  
Judy Y. Weltman ◽  
Niki Shah ◽  
Shannon Story ◽  
Johannes D. Veldhuis ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Area Under The Curve ◽  
Interactive Effects ◽  
Men And Women ◽  
Gh Secretion ◽  
Exercise Condition ◽  
Calculated Mass ◽  
Exercise Induced ◽  
Serum Gh ◽  
Secretion Rates

We examined gender differences in growth hormone (GH) secretion during rest and exercise. Eighteen subjects (9 women and 9 men) were tested on two occasions each [resting condition (R) and exercise condition (Ex)]. Blood was sampled at 10-min intervals from 0600 to 1200 and was assayed for GH by chemiluminescence. At R, women had a 3.69-fold greater mean calculated mass of GH secreted per burst compared with men (5.4 ± 1.0 vs. 1.7 ± 0.4 μg/l, respectively) and higher basal (interpulse) GH secretion rates, which resulted in greater GH production rates and serum GH area under the curve (AUC; 1,107 ± 194 vs. 595 ± 146 μg ⋅ l−1⋅ min, women vs. men; P = 0.04). Compared with R, Ex resulted in greater mean mass of GH secreted per burst, greater mean GH secretory burst amplitude, and greater GH AUC (1,196 ± 211 vs. 506 ± 90 μg ⋅ l−1⋅ min, Ex vs. R, respectivley; P < 0.001). During Ex, women attained maximal serum GH concentrations significantly earlier than men (24 vs. 32 min after initiation of Ex, respectively; P = 0.004). Despite this temporal disparity, both genders had similar maximal serum GH concentrations. The change in AUC (adjusted for unequal baselines) was similar for men and women (593 ± 201 vs. 811 ± 268 μg ⋅ l−1⋅ min), but there were significant gender-by-condition interactive effects on GH secretory burst mass, pulsatile GH production rate, and maximal serum GH concentration. We conclude that, although women exhibit greater absolute GH secretion rates than men both at rest and during exercise, exercise evokes a similar incremental GH response in men and women. Thus the magnitude of the incremental secretory GH response is not gender dependent.

Cholinergic modulation of GH secretion in acromegalic patients before and after pituitary surgery

1992 ◽  
Vol 127 (6) ◽  
pp. 489-493 ◽  
Author(s):  
Leon Fiszlejder ◽  
Olga Penacini ◽  
Susana Ratz ◽  
Adriana Oneto ◽  
Maria Storani ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Pituitary Surgery ◽  
Normal Subjects ◽  
Physiological Control ◽  
Gh Secretion ◽  
Pathophysiological Role ◽  
Before And After ◽  
Transsphenoidal Adenomectomy ◽  
Ghrh Test

Cholinergic neurotransmission exerts a physiological control on GH secretion. Pirenzepine (Pz), an antagonist of muscarinic receptors, by enhancing hypothalamic somatostatin release, inhibits stimulated GH secretion in normal subjects but not in acromegalic patients. To address the hypothesis that a feedback effect of GH hypersecretion can be involved in this condition, GH responses to GHRH 1–29, 1 μg/kg iv, with and without administration of Pz, 40mg iv before tests, were investigated in eight acromegalic patients, before and 20–30 days after transsphenoidal adenomectomy. Pz diminished (p<0.001) the incremental area under the curve (AUC) of GH responses to GHRH in seven normal controls. In contrast, GHRH responsiveness in untreated acromegalic patients was not affected by Pz. Postoperative basal GH levels decreased by 62.4±14.9% (p<0.01). Pz inhibited GH responses to GHRH (p<0.01). Furthermore, a direct relationship (r = 0.73, p<0.01) between basal concentrations and the AUC of GH responses following Pz plus GHRH-test was found. The finding that muscarinic receptor activity recovered after the reduction of serum GH basal levels by pituitary surgery lends support to the proposed pathophysiological role of GH excess as a possible determinant factor in cholinergicsomatostatinergic dysfunction in acromegaly.

Circulating growth hormone forms in Type 1 diabetic subjects: comparison with normal subjects and acromegalics

1986 ◽  
Vol 112 (4) ◽  
pp. 547-551 ◽  
Author(s):  
L. A. MacFarlane ◽  
Susan Stafford ◽  
A. D. Wright
Keyword(s):  
Growth Hormone ◽  
Normal Subjects ◽  
Molecular Forms ◽  
Diabetic Patients ◽  
Strongly Correlated ◽  
Gh Secretion ◽  
Main Component ◽  
Type 1 Diabetic Patients ◽  
Serum Gh

Abstract. The molecular forms of growth hormone (GH) in serum from 18 Type 1 diabetic patients with poor metabolic control were analysed using sephadex G-100 chromatography. The profiles obtained were compared with those from normal subjects whose GH secretion was stimulated by exercise and hypoglycaemia and eight acromegalic patients. In the three groups three distinct GH forms were found: little (monomeric), big and big-big-GH. Samples from normal subjects contained 45% little-GH which was less than samples from the diabetics and acromegalics (53% and 65%, respectively, P <0.01). Further samples from normal subjects after the onset of hypoglycaemia showed an increase in little-GH. In the three groups, the higher the proportion of little-GH, the lower the proportion of big-big-GH, while the proportion of big-GH remained similar. In the acromegalics the proportion of little-GH was strongly correlated with the log concentration of serum GH. As little-GH is cleared from the circulation quicker than the larger forms these data indicate that the main component of the frequent surges of GH secretion in poorly controlled Type 1 diabetic subjects is little-GH (monomeric forms). The sustained release of GH found in acromegaly is composed largely of monomeric forms.

scholarly journals Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

2000 ◽  
pp. 203-211
Author(s):  
JJ Diez ◽  
P Iglesias ◽  
J Sastre ◽  
A Gomez-Pan
Keyword(s):  
Growth Hormone ◽  
Normal Subjects ◽  
Thyrotropin Releasing Hormone ◽  
Constant Infusion ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Control Subjects ◽  
Human Erythropoietin ◽  
Trh Stimulation ◽  
Tsh Secretion

OBJECTIVE: Our aim has been to evaluate the effects of i.v. infusion of recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients. METHODS: We studied 16 patients (8 females, aged 29-68 years) with active acromegaly and 12 control subjects (7 females, 24-65 years). All participants were tested with TRH (400 microg i.v. as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH injection) on different days. Blood samples were obtained between -30 and 120 min for GH and PRL determinations, and between -30 and 90 min for TSH determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis. RESULTS: Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any significant change in GH secretion in normal subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ from those values found in controls. When TRH was injected during the rhEPO infusion, a significant (P<0.05) increase in PRL concentrations at 15-120 min was found in acromegalic patients. Accordingly, the PRL peak and the AUC for PRL secretion were significantly increased in patients. Infusion with rhEPO had no effect on TRH-induced PRL release in control subjects. Baseline TSH concentrations, as well as the TSH peak and the AUC after TRH, were significantly lower in patients than in controls. Infusion with rhEPO modified neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers. CONCLUSION: Results in patients with acromegaly suggest that (i) the paradoxical GH response to TRH is not modified by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.

EFFECT OF AMINOPHYLLINE ON GROWTH HORMONE SECRETION IN MAN

1974 ◽  
Vol 76 (3) ◽  
pp. 488-494 ◽  
Author(s):  
M. Peracchi ◽  
F. Cavagnini ◽  
A. E. Pontiroli ◽  
U. Raggi ◽  
A. Malinverni ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Intravenous Infusion ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Normal Subjects ◽  
Gh Secretion ◽  
Inhibiting Effect ◽  
Plasma Ffa ◽  
Serum Gh

ABSTRACT The effects of intravenously administered aminophylline on growth hormone (GH) secretion have been studied in sixteen normal subjects and four acromegalic patients. Intravenous infusion of theophylline ethylenediamine 480 mg over a 30 min period did not alter the blood glucose and serum GH levels in six normal subjects but raised the plasma FFA by 88 %. By contrast, in four acromegalic patients theophylline administration resulted in a fall of the serum GH levels by 17.6–51.7 %, mean 36.5%. In ten normal subjects the infusion of the drug clearly blunted the GH response to insulin hypoglycaemia without modifying the decrease in blood glucose and plasma FFA induced by insulin: mean peak GH values decreased from 32.7 ± 3.39 to 21.4 ± 4.10 ng/ml (P < 0.025). These data seem to indicate that theophylline has an overall inhibiting effect on the hypothalamic-hypophyseal axis for GH secretion.

α-Adrenoreceptor blockade with thymoxamine reduces basal thyrotrophin levels but does not influence circadian thyrotrophin changes in man

1987 ◽  
Vol 115 (1) ◽  
pp. 187-191 ◽  
Author(s):  
R. Valcavi ◽  
C. Dieguez ◽  
C. Azzarito ◽  
C. Artioli ◽  
I. Portioli ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Normal Subjects ◽  
Adrenergic Blockade ◽  
Adrenergic Stimulation ◽  
Incremental Change ◽  
Tsh Secretion ◽  
Nocturnal Increase ◽  
Hypothyroid Patients ◽  
Control Infusion ◽  
Tsh Levels

ABSTRACT We have tested the hypothesis that α-adrenergic drive is involved in the nocturnal increase in TSH in man. Seven mildly hypothyroid women (basal TSH levels 5·0–11·0 mU/1), aged 38–60 years, and nine euthyroid women, aged 27–60 years, were studied. Subjects underwent α-adrenergic blockade by infusion of thymoxamine (210 μg/min from 19.00 to 24.00 h); the same women were used as controls, with saline infused on different nights. Subjects were not allowed to sleep during the study period. A clear evening rise in basal TSH levels was apparent in both normal subjects and patients. Although overall secretion of TSH was slightly decreased in normal subjects (mean ± s.e.m. area under the curve, 29·93 ± 0·96 vs 30·71 ±mU/1 per h; P<0·05), thymoxamine infusion did not produce any major alteration in the gradual rise in TSH levels during the evening (incremental change above baseline +0·96± 0·21 during control infusion and + 0·97 ± 0·27 mU/1 during thymoxamine infusion). In mildly hypothyroid patients the TSH changes were exaggerated and α-adrenergic blockade caused a reduction in basal TSH levels and a delayed rise in TSH (incremental change above baseline +2·93 ± 1·42 during control infusion and +2·26 ± 0·73 mU/1 during thymoxamine infusion; P < 0·02). Overall TSH secretion was significantly decreased by thymoxamine (mean ± s.e.m. area 106 ± 2·45 mU/1 per h vs 123·32 ± 3·68 in the control study; P<0·0001). As expected, no circadian change was observed in basal prolactin levels in either controls or patients. Although α-adrenergic pathways may play a role in modulating the nocturnal increase in basal TSH levels, our data suggest that the evening rise in TSH is not a consequence of a primary increase in α-adrenergic drive. The increased TSH changes of mildly hypothyroid patients may, however, be sustained by increased central α-adrenergic stimulation of the TSH secretion. J. Endocr. (1987) 115, 187–191

scholarly journals The role of endogenous GHRH in arginine-, insulin-, clonidine- and l-dopa-induced GH release in normal subjects

2002 ◽  
Vol 146 (2) ◽  
pp. 197-202 ◽  
Author(s):  
K Hanew ◽  
A Utsumi
Keyword(s):  
Healthy Adult ◽  
Normal Subjects ◽  
Insulin Administration ◽  
Adult Males ◽  
Gh Secretion ◽  
Maximal Stimulation ◽  
Combined Administration ◽  
Serum Gh ◽  
Stimulation Of

OBJECTIVE: The role of endogenous GHRH in arginine-, insulin-, clonidine- and l-dopa-induced GH secretion was studied in man using a GHRH antagonist (GHRH-Ant). DESIGN: Ten healthy adult males were studied for serum GH responses to arginine or insulin singly, or sequentially 120 min after GHRH injection with or without combined administration of GHRH-Ant. Further, GHRH, clonidine or l-dopa were sequentially administered to these subjects 120 min after the GHRH injection. RESULTS: The combined administration of GHRH-Ant distinctly inhibited the arginine- and insulin-induced GH release. When these four agents were sequentially administered 120 min after GHRH injection, the GH responses to clonidine and l-dopa disappeared completely while clear responses were observed to arginine and insulin administration. These responses to arginine and insulin were also completely inhibited by the combined administration of GHRH-Ant. CONCLUSIONS: These results indicate that clonidine and l-dopa stimulate GH secretion mainly through the release of hypothalamic GHRH, and that arginine- and insulin-induced hypoglycaemia stimulate GH secretion mainly through the inhibition of hypothalamic somatostatin release. However, the presence of endogenous hypothalamic GHRH seems to be essential for the maximal stimulation of GH release induced by arginine and insulin.

Nasal Absorption of Growth Hormone in Normal Subjects: Studies with Four Different Formulations

1994 ◽  
Vol 28 (7-8) ◽  
pp. 845-848 ◽  
Author(s):  
Torben Laursen ◽  
Per Ovesen ◽  
Birgitte Grandjean ◽  
Sigrid Jensen ◽  
Jens Otto L. Jørgensen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Maximum Concentration ◽  
Relative Concentration ◽  
Elevated Serum ◽  
Area Under The Curve ◽  
Random Order ◽  
Normal Subjects ◽  
Nasal Symptom ◽  
Subcutaneous Injections ◽  
Gh Secretion

OBJECTIVE: Current growth hormone (GH) therapy with daily subcutaneous injections results in elevated serum concentrations of GH lasting for several hours, whereas physiologic GH secretion is characterized by a short-duration peak and low basal concentrations. A closer imitation of this pattern might be achieved by administering GH nasally. We studied the effect on the absorption of nasally administered human GH of increasing concentrations of the enhancer didecanoyl-L-α-phosphatidylcholine (DDPC). DESIGN: Four formulations of nasal GH containing the enhancer DDPC in the relative concentrations 0, 4,8, and 16% w/w were administered in random order. SETTING: Participants were admitted to the hospital during the four study periods. INTERVENTIONS: On four occasions the subjects received GH 6 IU (2 mg) in each nostril. Blood was sampled frequently for four hours. Anterior rhinoscopy was performed at 0 and 4 h. During the study the subjects completed a questionnaire to record nasal symptoms. PATIENTS: Sixteen healthy subjects were examined at 0800 h after an overnight fast. MAIN OUTCOME MEASURES: Bioavailability of a nasal preparation of human GH: area under the curve (AUC), the maximum concentration(Cmax), and the time to reach maximum concentration (tmax). Scores for each nasal symptom were recorded as were the total scores. RESULTS: AUC, Cmax, and tmax,. were not significantly affected by increasing the DDPC concentration from 0 to 4 percent or from 8 to 16 percent. AUC and Cmax, however, increased significantly when the concentration of DDPC was changed from 4 to 8 percent. Mean (±SD) AUC (μg·h/L) increased from 20.51 ± 10.53(4 percent)to 46.14 ± 34.59 (8 percent), (p<0.005). Mean (±SD) of Cmax (μg.L) increased from 11.11 ± 5.02 (4 percent) to 28.22 ± 20.85 (8 percent), (p=0.OO2). Mean (±SD) of tmax (min) was not significantly different on the four occasions(range 40.6 ± 36.4 to 61.0 ± 45.2 min, p=0.13). The symptom scores (range 17.56–21.5, maximum 360) were not significantly different (p=0.59). CONCLUSIONS: Increasing the relative concentration of the enhancer DDPC increases the absorption of nasally administered GH.

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