Influence of chronic naltrexone treatment on growth hormone secretion in normal subjects

1997 ◽  
pp. 631-634 ◽  
Author(s):  
P Villa ◽  
D Valle ◽  
L De Marinis ◽  
A Mancini ◽  
A Bianchi ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Normal Subjects ◽  
Molar Ratio ◽  
Normal Female ◽  
Gh Secretion ◽  
Igf I ◽  
Before And After ◽  
Ghrh Test ◽  
Igfbp 3

OBJECTIVE: To verify if a chronic opioid blockade could affect the GH/IGF-I axis. DESIGN: We have investigated the effects of naltrexone (NTX) treatment on GH response to GHRH in normal women. METHODS: GHRH test (50 micrograms i.v.) performed in seven normal female volunteers (age 25-38 years, with a body mass index ranging from 19.8 to 23.1 kg/m2) before and after 4-weeks NTX treatment (50 mg p.o. daily). RESULTS: Basal GH, IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3) plasma levels and the IGF-I/IGFBP-3 molar ratio remained unaffected by NTX. NTX significantly reduced the GH peak values (15.52 +/- 3.59 vs 4.78 +/- 0.49 micrograms/l; P < 0.01), and GH area under curve (918.93 +/- 253.96 vs 401.09 +/- 79.63 micrograms/l; P < 0.01). CONCLUSIONS: This finding suggests that the long-term opioid receptor blockade has an inhibitory role on GHRH-induced GH secretion. A central influence on neurotransmitter control of GH might be hypothesised. The inhibition of stimulated GH release, without interference with the basal level, could indicate an enhanced somatostatin secretion and/or activity. Opioids could be involved only in the regulation of GH dynamics and not in basal secretion. Nevertheless, a direct involvement of opioids at the pituitary level, which could be modified by NTX, cannot be excluded.

Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men

2007 ◽  
Vol 293 (3) ◽  
pp. E769-E775 ◽  
Author(s):  
Ranganath Muniyappa ◽  
John D. Sorkin ◽  
Johannes D. Veldhuis ◽  
S. Mitchell Harman ◽  
Thomas Münzer ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Low Dose ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Older Men ◽  
Gh Secretion ◽  
Aging Men ◽  
Igf I ◽  
Igfbp 3

Circulating testosterone (T) and GH/IGF-I are diminished in healthy aging men. Short-term administration of high doses of T augments GH secretion in older men. However, effects of long-term, low-dose T supplementation on GH secretion are unknown. Our objective was to evaluate effects of long-term, low-dose T administration on nocturnal GH secretory dynamics and AM concentrations of IGF-I and IGFBP-3 in healthy older men (65–88 yr, n = 34) with low-normal T and IGF-I. In a double-masked, placebo-controlled, randomized study we assessed effects of low-dose T supplementation (100 mg im every 2 wk) for 26 wk on nocturnal GH secretory dynamics [8 PM to 8 AM, Q20 min sampling, analyzed by multiparameter deconvolution and approximate entropy (ApEn) algorithms]. The results were that T administration increased serum total T by 33% ( P = 0.004) and E2 by 31% ( P = 0.009) and decreased SHBG by 17% ( P = 0.002) vs. placebo. T supplementation increased nocturnal integrated GH concentrations by 60% ( P = 0.02) and pulsatile GH secretion by 79% ( P = 0.05), primarily due to a twofold increase in GH secretory burst mass ( P = 0.02) and a 1.9-fold increase in basal GH secretion rate ( P = 0.05) vs. placebo. There were no significant changes in GH burst frequency or orderliness of GH release (ApEn). IGF-I levels increased by 22% ( P = 0.02), with no significant change in IGFBP-3 levels after T vs. placebo. We conclude that low-dose T supplementation for 26 wk increases spontaneous nocturnal GH secretion and morning serum IGF-I concentrations in healthy older men.

scholarly journals Estradiol Potentiates Ghrelin-Stimulated Pulsatile Growth Hormone Secretion in Postmenopausal Women

2006 ◽  
Vol 91 (9) ◽  
pp. 3559-3565 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Daniel M. Keenan ◽  
Ali Iranmanesh ◽  
Kristi Mielke ◽  
John M. Miles ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Medical Center ◽  
Academic Medical Center ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Follicular Phase ◽  
Gh Secretion ◽  
Igf I ◽  
Late Follicular Phase ◽  
Igfbp 3

Abstract Context: Ghrelin and an estrogen-rich milieu individually amplify pulsatile GH secretion by increasing the amount of hormone released per burst. However, how these distinct agonists interact in controlling pulsatile GH output is not known. Objective: The objective of the study was to test the hypothesis that elevated estradiol (E2) concentrations potentiate hypothalamo-pituitary responses to a near-physiological ghrelin stimulus. Design: This was a double-blind, placebo-controlled, prospectively randomized, parallel-cohort study. Setting: The study was conducted at an academic medical center. Subjects: Twenty-one postmenopausal women participated in the study. Interventions: Eleven subjects received placebo (Pl) and 10 others E2 transdermally in escalating doses over 3 wk to mimic late follicular-phase E2 concentrations. Saline or a submaximally stimulatory amount of ghrelin (0.3 μg/kg) was infused iv on separate randomly ordered mornings fasting after 17–21 d of Pl or E2 administration. Outcomes: Outcomes included serum concentrations of E2, ghrelin, GH, IGF-I, IGF binding protein (IGFBP)-1 and IGFBP-3, and the estimated mass and waveform of stimulated GH secretory bursts. Results: Administration of E2 yielded late follicular-phase E2 concentrations. Compared with Pl, E2 did not alter ghrelin concentrations but reduced IGF-I and IGFBP-3 and elevated IGFBP-1 concentrations. Compared with saline, ghrelin infusion amplified pulsatile GH secretion by 7.1-fold (P &lt; 0.01). The effect of E2 alone was 2.0-fold placebo and that of combined ghrelin/E2 10.4-fold (P &lt; 0.01). Ghrelin and E2 accelerated initial GH release individually but nonadditively by more than 2-fold (P &lt; 0.01). Conclusions: Estrogen augments ghrelin’s near-physiological stimulation of pulsatile GH secretion and mimics ghrelin’s acceleration of initial GH release. Thus, we hypothesize that estrogen and a GH secretagogue act via independent as well as convergent mechanisms.

EFFECT OF l-DOPA ADMINISTRATION ON GROWTH HORMONE SECRETION IN NORMAL SUBJECTS AND PARKINSONIAN PATIENTS

1972 ◽  
Vol 54 (3) ◽  
pp. 425-433 ◽  
Author(s):  
F. CAVAGNINI ◽  
M. PERACCHI ◽  
G. SCOTTI ◽  
U. RAGGI ◽  
A. E. PONTIROLI ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Normal Subjects ◽  
Significant Rise ◽  
Arginine Infusion ◽  
Physiological Regulation ◽  
Gh Secretion ◽  
Before And After ◽  
Serum Gh

SUMMARY The effect of both oral and intravenous administration of l-DOPA on growth hormone (GH) secretion was studied in a group of normal volunteers: a significant rise of serum GH levels was observed in both cases. Growth hormone release in response to insulin hypoglycaemia and to arginine infusion was evaluated in a group of Parkinsonian patients before and after 25 days' treatment with l-DOPA plus a DOPA-decarboxylase inhibitor. In addition, GH response to the above stimuli was studied in a group of patients who had been under treatment for more than 6 months with l-DOPA alone. In untreated Parkinsonian patients, GH response to insulin hypoglycaemia was at the lower limit of normal range while arginine-induced GH release was significantly reduced. Treatment with l-DOPA did not increase GH responses. Some possible interpretations of the results are discussed. The findings support the possibility that dopamine plays a role in the physiological regulation of GH secretion, as in the case of luteinizing hormone, follicle-stimulating hormone and prolactin release.

Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans

2002 ◽  
Vol 283 (5) ◽  
pp. E1008-E1015 ◽  
Author(s):  
Craig A. Jaffe ◽  
D. Kim Turgeon ◽  
Kenneth Lown ◽  
Roberta Demott-Friberg ◽  
Paul B. Watkins
Keyword(s):  
Gender Differences ◽  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Treatment Protocol ◽  
Metabolic Effects ◽  
Gh Secretion ◽  
Igf I ◽  
Daily Dose ◽  
Igfbp 3

The importance of gender-specific growth hormone (GH) secretion pattern in the regulation of growth and metabolism has been demonstrated clearly in rodents. We recently showed that GH secretion in humans is also sexually dimorphic. Whether GH secretion pattern regulates the metabolic effects of GH in humans is largely unknown. To address this question, we administered the same daily intravenous dose of GH (0.5 mg · m−2 · day−1) for 8 days in different patterns to nine GH-deficient adults. Each subject was studied on four occasions: protocol 1 (no treatment), protocol 2 (80% daily dose at 0100 and 10% daily dose at 0900 and 1700), protocol 3 (8 equal boluses every 3 h), and protocol 4 (continuous GH infusion). The effects of GH pattern on serum IGF-I, IGF-binding protein (IGFBP)-3, osteocalcin, and urine deoxypyridinoline were measured. Hepatic CYP1A2 and CYP3A4 activities were assessed by the caffeine and erythromycin breath tests, respectively. Protocols 3 and 4 were the most effective in increasing serum IGF-I and IGFBP-3, whereas protocols administering pulsatile GH had the greatest effects on markers of bone formation and resorption. All GH treatments decreased CYP1A2 activity, and the effect was greatest for pulsatile GH. Pulsatile GH decreased, whereas continuous GH infusion increased, CYP3A4 activity. These data demonstrate that GH pulse pattern is an independent parameter of GH action in humans. Gender differences in drug metabolism and, potentially, gender differences in growth rate may be explained by sex-specific GH secretion patterns.

Effect of actively immunizing sheep against growth hormone-releasing hormone or somatostatin on spontaneous pulsatile and neostigmine-induced growth hormone secretion

1995 ◽  
Vol 144 (1) ◽  
pp. 83-90 ◽  
Author(s):  
E Magnan ◽  
L Mazzocchi ◽  
M Cataldi ◽  
V Guillaume ◽  
A Dutour ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Role ◽  
Gh Secretion ◽  
Igf I ◽  
Plasma Gh ◽  
Hypophysial Portal

Abstract The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90

scholarly journals Estradiol Supplementation in Postmenopausal Women Attenuates Suppression of Pulsatile Growth Hormone Secretion by Recombinant Human Insulin-like Growth Factor Type I

2008 ◽  
Vol 93 (11) ◽  
pp. 4471-4478 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Daniel M. Keenan ◽  
Joy N. Bailey ◽  
Adenborduin Adeniji ◽  
John M. Miles ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Negative Feedback ◽  
Academic Medical Center ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Approximate Entropy ◽  
Type I ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Igf I

Background: Why pulsatile GH secretion declines in estrogen-deficient postmenopausal individuals remains unknown. One possibility is that estrogen not only enhances stimulation by secretagogues but also attenuates negative feedback by systemic IGF-I. Site: The study took place at an academic medical center. Subjects: Subjects were healthy postmenopausal women (n = 25). Methods: The study included randomized assignment to estradiol (n = 13) or placebo (n = 12) administration for 16 d and randomly ordered administration of 0, 1.0, 1.5, and 2.0 mg/m2 recombinant human IGF-I sc on separate days fasting. Analysis: Deconvolution analysis of pulsatile and basal GH secretion and approximate entropy (pattern-regularity) analysis were done to quantify feedback effects of IGF-I. Outcomes: Recombinant human IGF-I injections increased mean and peak serum IGF-I concentrations dose dependently (P &lt; 0.001) and suppressed mean GH concentrations (P &lt; 0.001), pulsatile GH secretion (P = 0.001), and approximate entropy (P &lt; 0.001). Decreased GH secretion was due to reduced secretory-burst mass (P = 0.005) and frequency (P &lt; 0.001) but not basal GH release (P = 0.52). Estradiol supplementation lowered endogenous, but did not alter infused, IGF-I concentrations while elevating mean GH concentrations (P = 0.012) and stimulating pulsatile (P = 0.008) and basal (P &lt; 0.001) GH secretion. Estrogen attenuated IGF-I’s inhibition of pulsatile GH secretion (P = 0.042) but was unable to restore physiological GH pulse frequency or normalize approximate entropy. Conclusion: Short-term estrogen replacement in postmenopausal women selectively mutes IGF-I-mediated feedback on pulsatile GH secretion. Disinhibition of negative feedback thus confers a novel mechanism by which estrogen may obviate hyposomatotropism.

Negative feedback of insulin-like growth factor-I on growth hormone secretion by porcine pituitary cells

1995 ◽  
Vol 75 (1) ◽  
pp. 57-61 ◽  
Author(s):  
C. Farmer ◽  
H. Lapierre
Keyword(s):  
Growth Hormone ◽  
Negative Feedback ◽  
Culture Media ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Age Related ◽  
Igf I

Pituitaries from female Yorkshire pig fetuses (90 d, n = 26; 110 d, n = 17) and 6-mo-old pigs (n = 5) were enzymatically dispersed, plated, and cultured for 47 h. The cells were then rinsed and incubated for 22 h with testing media containing 0, 50, 100, 200, 300 or 400 ng mL−1 of IGF-I. Half of the wells from each concentration of IGF-I were then incubated for an additional 3 h with concentrations of IGF-I similar to those in the previous incubation, while the other half also had GRF added to the testing media to reach a final concentration of 10−8 M. Culture media were then collected from all the wells, were frozen, and later assayed for GH. Irrespective of whether GRF was present, IGF-I decreased pituitary secretion of GH (P < 0.001). A significant negative response to IGF-I was already present at the dose of 50 ng mL−1 (P < 0.0001). However, the extent of the GH response to IGF-I seen in pigs of various ages differed depending on whether GRF was present. The present results therefore establish that IGF-I does exert a negative feedback on pituitary GH secretion in swine and that the age-related changes in this feedback are dependent on the presence of GRF. In swine, it appears that high circulating concentrations of GH in late-gestation fetuses are not a result of a lesser sensitivity of the somatotroph to the inhibitory actions of IGF-I. Key words: Pig, cell culture, pituitary, IGF-I, growth hormone, age

scholarly journals Regulated recovery of pulsatile growth hormone secretion from negative feedback: a preclinical investigation

2011 ◽  
Vol 301 (4) ◽  
pp. R1143-R1152 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Cyril Y. Bowers
Keyword(s):  
Body Mass Index ◽  
Growth Hormone ◽  
Body Mass ◽  
Negative Feedback ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Gh Secretion ◽  
Model Free ◽  
Preclinical Investigation ◽  
Igf I

Although stimulatory (feedforward) and inhibitory (feedback) dynamics jointly control neurohormone secretion, the factors that supervise feedback restraint are poorly understood. To parse the regulation of growth hormone (GH) escape from negative feedback, 25 healthy men and women were studied eight times each during an experimental GH feedback clamp. The clamp comprised combined bolus infusion of GH or saline and continuous stimulation by saline GH-releasing hormone (GHRH), GHRP-2, or both peptides after randomly ordered supplementation with placebo (both sexes) vs. E2 (estrogen; women) and T (testosterone; men). Endpoints were GH pulsatility and entropy (a model-free measure of feedback quenching). Gender determined recovery of pulsatile GH secretion from negative feedback in all four secretagog regimens (0.003 ≤ P ≤ 0.017 for women>men). Peptidyl secretagog controlled the mass, number, and duration of feedback-inhibited GH secretory bursts (each, P < 0.001). E2/T administration potentiated both pulsatile ( P = 0.006) and entropic ( P < 0.001) modes of GH recovery. IGF-I positively predicted the escape of GH secretory burst number and mode ( P = 0.022), whereas body mass index negatively forecast GH secretory burst number and mass ( P = 0.005). The composite of gender, body mass index, E2, IGF-I, and peptidyl secretagog strongly regulates the escape of pulsatile and entropic GH secretion from autonegative feedback. The ensemble factors identified in this preclinical investigation enlarge the dynamic model of GH control in humans.

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.

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