IGF feedback effects on growth hormone secretion in ewes: evidence for action at the pituitary but not the hypothalamic level

1995 ◽  
Vol 144 (2) ◽  
pp. 323-331 ◽  
Author(s):  
T P Fletcher ◽  
G B Thomas ◽  
F R Dunshea ◽  
L G Moore ◽  
I J Clarke
Keyword(s):  
Stainless Steel ◽  
Negative Feedback ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Feedback Effects ◽  
Peripheral Tissues ◽  
Blood Samples ◽  
Gh Secretion ◽  
Igf I ◽  
Plasma Gh

Abstract The putative negative feedback effects of IGF-I and IGF-II on GH secretion were tested by intracerebroventricular (icv) and intrapituitary administration to sheep. Over two consecutive days, serial jugular blood samples were taken at 10 min intervals for 6 h from ewes (n=3/group) fitted with indwelling stainless steel cannulae into the lateral or third cerebral ventricles. The sheep were injected (icv) with either vehicle or purified ovine IGF-I (2, 4 or 8 μg). IGF-I injection had no effect on plasma GH secretion. Serial blood samples were taken from a second group of nine ewes in which ovine or recombinant human (rh) IGF-I was infused (2·5 μg/h for 2 h) into the third ventricle; once again, IGF-I failed to affect the episodic pattern of GH secretion. Three ewes fitted with indwelling stainless steel cannulae placed in the anterior pituitary gland were consecutively infused with either ovine or rhIGF-I (2·5 μg/h for 2 h) or vehicle. Plasma GH concentrations were suppressed in 3/3 sheep from 1–1·5 h after the commencement of infusion and GH levels remained low for the remainder of the sampling period. In another group of five ewes synergistic effects of IGF-I and IGF-II on GH secretion were tested by icv infusion of rhIGF-I, rhIGF-II, or rhIGF-I+rhIGF-II (5 μg/h for 2 h) or vehicle (sterile 10 mm HCl/saline). Each sheep received each treatment in a randomised design. Infusion (icv) of IGF-I and IGF-II alone or in combination failed to alter GH secretion. These observations suggest that IGF-I derived from peripheral tissues may modulate GH release at the pituitary level but that IGF-I acts neither alone nor in conjunction with IGF-II as a negative feedback regulator of GH secretion via the hypothalamus in the ewe. Journal of Endocrinology (1995) 144, 323–331

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 < 0.001) and suppressed mean GH concentrations (P < 0.001), pulsatile GH secretion (P = 0.001), and approximate entropy (P < 0.001). Decreased GH secretion was due to reduced secretory-burst mass (P = 0.005) and frequency (P < 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 < 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.

Prolonged fasting or clonidine can restore the defective growth hormone secretion in old dogs

1989 ◽  
Vol 121 (2) ◽  
pp. 177-184 ◽  
Author(s):  
Silvano G. Cella ◽  
Valerio Moiraghi ◽  
Francesco Minuto ◽  
Antonina Barreca ◽  
Daniela Cocchi ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Peak Frequency ◽  
Prolonged Fasting ◽  
Total Peak Area ◽  
Gh Secretion ◽  
Age Related ◽  
Adrenoceptor Agonist ◽  
Baseline Conditions ◽  
Plasma Gh

Abstract. Age-related changes in GH secretion were studied in the dog. In preliminary experiments, administration of GH-relasing hormone (GHRH-40, 2 μg/kg, iv) or the α2-adrenoceptor agonist clonidine (4 μg/kg, iv) elicited significantly higher plasma GH rises in 3 to 4 years old than in 10 to 14 years old beagle dogs. The pulsatile patterns of GH secretion in both young and old dogs under baseline conditions and after prolonged fasting or clonidine administration were studied. Samples were taken every 10 min from 09.00 to 15.00 h from five young and five old dogs of both sexes. Under baseline conditions, GH peak frequency, total peak area, and integrated GH secretion were significantly lower in old than in young dogs. In old dogs, 5-day complete fasting or 14-day clonidine administration (75 μg/dog, po, twice daily) increased the frequency and amplitude of spontaneous GH bursts, the total peak area, and the integrated GH secretion. After either stimulus, the GH secretory pattern was quantitatively and qualitatively indistinguishable from that of young dogs under baseline conditions. Similarly, the foregoing indices were significantly increased in young dogs by either stimulus, except for the inability of clonidine to affect peak frequency. These data demonstrate that the defective GH secretion in old dogs is not irreversible, since it is normalized when old dogs are exposed to central nervous system-directed stimuli.

Growth hormone secretion in stalk-sectioned rats

1991 ◽  
Vol 124 (6) ◽  
pp. 700-706 ◽  
Author(s):  
Jun Kamegai ◽  
Ichiji Wakabayashi ◽  
Hitoshi Sugihara ◽  
Shiro Minami ◽  
Taiko Kitamura ◽  
...  
Keyword(s):  
Adrenal Glands ◽  
Gh Deficiency ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Male Rats ◽  
Gh Secretion ◽  
The Face ◽  
Prolactin Response ◽  
Plasma Gh ◽  
Trough Levels

Abstract. Idiopathic pituitary GH deficiency appears to result from neonatal disruption of hypophyseal portal vessels in the majority of patients. To examine the mechanism of GH deficiency associated with the disease, the effect of pituitary stalk section on GH secretion was studied in rats. Adult male rats were subjected to stalk section without inserting an impermeable membrane between the cut ends. They were studied 3 to 4 weeks after surgery. In stalk-sectioned rats, pituitary weight, body weight and hypothalamic SRIH content were significantly reduced as compared with sham-operated rats. Hypothalamic GHRH content, plasma T3, T4, corticosterone and testosterone levels, and weights of testes remove and adrenal glands were comparable in the two groups. Plasma GH profiles of sham-operated rats showed characteristic periodic pulses occurring at 2.5-3 h intervals with intervening trough period. In stalk-sectioned rats, plasma GH levels were low with small fluctuations, but GH levels were significantly higher than trough levels of sham-operated rats. The amount of GH secreted during a 6-h period as measured by planimetry was significantly reduced. To ascertain the regeneration of hypophyseal portal vessels, post SRIH rebound in GH secretion, which requires the presence of endogenous GHRH, was examined. Withdrawal of exogenous SRIH infusion triggered a large rebound GH secretion whose magnitude did not differ between groups. In stalk-sectioned rats, GH response to met-enkephalin analogue, FK 33-824, was not observed, whereas prolactin response to the secretagogue was observed in the majority of rats. It appears that in stalksectioned rats, hypophyseal portal circulation is re-established, but GHRH release from the hypothalamus is impaired in the face of sufficient supply of other hypophysiotropic hormones.

Somatostatin tonically inhibits growth hormone secretion in domestic fowl

1986 ◽  
Vol 111 (1) ◽  
pp. 91-97 ◽  
Author(s):  
S. Harvey ◽  
S.-K. Lam ◽  
T. R. Hall
Keyword(s):  
Growth Hormone ◽  
Domestic Fowl ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Passive Immunization ◽  
Inhibitory Effect ◽  
Gh Secretion ◽  
Basal Plasma ◽  
Plasma Gh

ABSTRACT Passive immunization of immature chickens with sheep somatostatin (SRIF) antiserum promptly increased the basal plasma GH concentration and augmented TRH-induced GH secretion. Although exogenous SRIF had no inhibitory effect on the basal GH concentration in untreated birds or birds pretreated with non-immune sheep serum, it suppressed the stimulatory effect of SRIF immunoneutralization on GH secretion. These results suggest that SRIF is physiologically involved in the control of GH secretion in birds, in which it appears to inhibit GH release tonically. J. Endocr. (1986) 111, 91–97

Physiological control of growth hormone secretion by thyrotrophin-releasing hormone in the domestic fowl

1985 ◽  
Vol 105 (3) ◽  
pp. 351-355 ◽  
Author(s):  
H. Klandorf ◽  
S. Harvey ◽  
H. M. Fraser
Keyword(s):  
Domestic Fowl ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Control ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Normal Sheep Serum ◽  
Plasma Gh

ABSTRACT Immature cockerels (4- to 5-weeks old) were passively immunized, with antiserum raised in sheep, against thyrotrophin-releasing hormone (TRH). The administration of TRH antiserum (anti-TRH) at doses of 0·5, 1·0 or 2·0 ml/kg lowered, within 1 h, the basal concentration of plasma GH for at least 24 h. The administration of normal sheep serum had no significant effect on the GH concentration in control birds. Although the GH response to TRH (1·0 or 10·0 μg/kg) was not impaired in birds treated 1 h previously with anti-TRH, prior incubation (at 39 °C for 1 h) of TRH (20 μg/ml) with an equal volume of anti-TRH completely suppressed the stimulatory effect of TRH (10 pg/kg) on GH secretion in vivo. These results suggest that TRH is physiologically involved in the hypothalamic control of GH secretion in the domestic fowl. J. Endocr. (1985) 105, 351–355

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.

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.

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