Species differences between male rat and ram pituitary somatostatin receptors involved in the inhibition of growth hormone secretion

1997 ◽  
pp. 545-555 ◽  
Author(s):  
N Briard ◽  
A Dutour ◽  
J Epelbaum ◽  
N Sauze ◽  
A Slama ◽  
...  
Keyword(s):  
Binding Sites ◽  
Hormone Secretion ◽  
Somatostatin Receptors ◽  
Growth Hormone Secretion ◽  
Male Rat ◽  
Receptor Subtype ◽  
Binding Properties ◽  
Binding Characteristics ◽  
Gh Secretion ◽  
Inhibition Of Growth

The sheep is a valuable model in which to study GH neuroregulation as its pattern of GH secretion is very close to that in humans. Furthermore, important differences in somatostatin (SRIH) action between rats and sheep have been found previously. Our goal was to compare in male rat and ram pituitaries the binding characteristics of somatostatin receptors and the effect of SRIH and 17 analogues on GH release. Using radioautography, SRIH binding was seen to be evenly distributed over the anterior pituitary of both species. In the binding assay, binding sites were three times more concentrated in rats than in sheep. Important interspecies differences in the action of SRIH and its analogues were found: they inhibited GH at lower concentrations in rats than in sheep. Seven peptides displayed greater inhibitory ability in sheep than in rats while three were more potent in rats. Agonistic potencies to inhibit GH release in rats were correlated with somatostatin receptors subtype 2 (sst2) affinities. Our data confirm and extend the quantitative differences between rat and sheep in SRIH inhibitory action on GH secretion and confirm that ligand-binding properties of a given receptor subtype cannot be extrapolated across species.

Participation of tri-iodothyronine and metabolic clearance rate in the inhibition of growth hormone secretion in thyroxine-treated domestic fowl

1990 ◽  
Vol 124 (2) ◽  
pp. 215-223 ◽  
Author(s):  
S. Harvey ◽  
H. Klandorf ◽  
C. G. Scanes
Keyword(s):  
Clearance Rate ◽  
Domestic Fowl ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Secretion Rate ◽  
Bolus Administration ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Gh Secretion ◽  
Inhibition Of Growth

ABSTRACT Surgical thyroidectomy increases basal and TRH-induced GH concentrations in the peripheral plasma of immature domestic fowl. Replacement therapy with thyroxine (T4; 100 μg/kg per day for 7 days, i.m.) suppressed the GH responses to thyroidectomy. Bolus administration of T4 (10 μg/kg, i.m.) to thyroidectomized birds promptly lowered the circulating GH concentrations, which remained suppressed for at least 4 h. Chronic (daily injections for 7 days) or acute (one injection) pretreatment of thyroidectomized birds with iopanoic acid (IOP; 40 mg/bird, i.m.) before the bolus administration of T4 attenuated, but did not prevent, inhibition of circulating GH levels by T4. Administration of IOP (40 mg/bird i.m.) 24 h and immediately before the administration of tri-iodothyronine (T3; 3 μg/kg, i.m.) or T4 (10 μg/kg, i.m.) also failed to suppress thyroidal inhibition of circulating GH concentrations in thyroidectomized birds. Administration of IOP alone had no effect on GH concentrations. Circulating T3 concentrations were not enhanced following the administration of T4 to IOP-treated birds, indicating its inhibition of hepatic monodeiodinase activity. The metabolic clearance rate (MCR) of 125I-labelled chicken GH in the plasma of thyroidectomized fowl was less than that in sham-thyroidectomized birds. Following pretreatment with T4 (100 μg/kg per day for 7 days) sham-thyroidectomized and thyroidectomized birds did not differ significantly in their MCR. The GH secretion rate in thyroidectomized birds was similar to that in sham-thyroidectomized birds and in both groups was markedly reduced following pretreatment with T4. These results demonstrate thyroidal inhibition of circulating GH concentrations in fowl. Both T3 and T4 inhibited GH concentrations and the effect of T4 was not simply due to its role as a T3 prohormone. In the absence of thyroid hormones, the MCR of GH was reduced but its secretion rate was not enhanced. A significant reduction of GH secretion rate occurs in response to exogenous T4, in the absence of any change in GH metabolism. Journal of Endocrinology (1990) 124, 215–223

Pre-exposure of rat anterior pituitary cells to somatostatin enhances subsequent growth hormone secretion

1991 ◽  
Vol 128 (1) ◽  
pp. 91-95 ◽  
Author(s):  
S. B. Richardson ◽  
S. Twente
Keyword(s):  
Anterior Pituitary ◽  
Monolayer Culture ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Role ◽  
Male Rat ◽  
Pituitary Cells ◽  
Subsequent Growth ◽  
Gh Secretion ◽  
Anterior Pituitary Cells

ABSTRACT The precise roles of GH-releasing factor (GRF) and somatostatin (SRIF) in the orchestration of pulsatile GH secretion have not yet been fully determined. We examined the interactions of rat GRF and SRIF, in the concentration ranges present in rat hypophysialportal blood, on the secretion of GH from dispersed male rat anterior pituitary cells in monolayer culture. The effects of exposing cells to GRF and/or SRIF (0·01–1·nmol/l) for 1 h were compared with the effects of preincubation of cells with SRIF before experimental incubations. As anticipated, the stimulatory effects of 0·1–1 nmol GRF/l were abolished by concurrent incubation with SRIF at an equimolar concentration, although SRIF, at these concentrations, did not significantly inhibit basal GH secretion. Conversely, pre-exposure to 0·1 nmol SRIF/l for 30 or 60 min, resulted in an increase in GH secretion during a subsequent 60-min incubation period, both in the absence or in the presence of GRF (0·01–1 nmol/l). Pretreatment with GRF caused increased responsivity to GRF rather than significant sensitization of the GH response to GRF. These observations demonstrate actions of SRIF, at low and probably physiological concentrations, which are more complex than those of a pure inhibitor of GH secretion. Pre-exposure of the pituitary to SRIF enhances subsequent GH secretion, suggesting that SRIF may play an additional physiological role in amplifying the GRF signal. Journal of Endocrinology (1991) 128, 91–95

Thyrotrophin-releasing hormone (TRH)-induced growth hormone secretion in fowl: binding of TRH to pituitary membranes

1989 ◽  
Vol 3 (1) ◽  
pp. 23-32 ◽  
Author(s):  
S. Harvey ◽  
J. S. Baidwan
Keyword(s):  
Binding Sites ◽  
Free Acid ◽  
Binding Capacity ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Thyrotrophin Releasing Hormone ◽  
Caudal Lobe ◽  
Gh Secretion ◽  
Cephalic Lobe ◽  
Number Of Binding Sites

ABSTRACT Heat-labile specific binding sites for [3H]3-methylhistidine2-TRH ([3H]Me-TRH) were demonstrated on chicken adenohypophysial membranes. These binding sites were of both high affinity (dissociation constant, Kd = 15·53 nm) and low capacity (maximum binding capacity, Bmax = 8·73 pmol/g tissue) and of low affinity (Kd = 104·5 nm) and high capacity (Bmax = 32·41 pmol/g). Binding of [3H]Me-TRH to the pituitary membranes was greater at 4 °C than at 39 °C and occurred with rate constants (k1) of 1·6× 106 and 3·39×106m-1 min-1 respectively. Dissociation of [3H]Me-TRH binding at 4 °C occurred with a rate constant (k-1) of 0·125 min-1. Binding sites for [3H]Me-TRH were found in the cephalic lobe of the pituitary gland (the location of most lactotrophs and thyrotrophs) and in the caudal lobe (the location of most somatotrophs). The number of binding sites was greater in the caudal lobe than in the cephalic lobe, although the affinity of [3H]Me-TRH binding did not differ. The binding of [3H]Me-TRH to caudal lobe membranes was displaced by Me-TRH, TRH, pGlu-His-Pro-Gly-NH2 and [Glu1]-TRH, with half-maximal effective doses of 33 nm, 70·7 nm, 1·23 μm and 22 μm respectively, but not by [Phe2]-TRH, TRH free acid or His-Pro-diketopiperazine. The number of caudal lobe binding sites for [3H]Me-TRH in old birds was less than that in young ones, and the number of binding sites was increased in birds deprived of food for 48 h. TRH-induced GH secretion in birds would thus appear to be mediated by specific receptors on caudal lobe somatotrophs, and these results suggest that physiological changes in GH secretion (during growth and periods of fasting) are causally related to the abundance of TRH-binding sites.

Insulin-like growth factor inhibition of growth hormone secretion

1986 ◽  
Vol 64 (5) ◽  
pp. 525-530 ◽  
Author(s):  
M. S. Sheppard ◽  
R. M. Bala
Keyword(s):  
Growth Hormone ◽  
Growth Factors ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Phosphodiesterase Inhibitor ◽  
Human Pancreas ◽  
Gh Secretion ◽  
Inhibition Of Growth ◽  
Low Concentrations ◽  
Methyl Xanthine

Somatomedins – insulin-like growth factors (SM/IGF) are growth hormone (GH) dependent serum growth factors. There is some evidence that IGF inhibit GH release (negative feedback) in 3- to 24-h incubations of cultured rat adenohypophysial cells. We have used acutely dispersed noncultured rat adenohypophysial cells to study the dynamics of IGF on GH secretion. In this system both IGF-I and IGF-II (100 ng/mL) slightly, but significantly, decrease the cumulative GH released by human pancreas growth hormone releasing factor 1–40 (GRF) and the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine. The inhibition is small (16%) and usually not statistically significant until 2 h of incubation. The inhibition with IGF is additive to that produced with low concentrations of somatostatin. The IGF also sigificantly decrease the rate of GH release in all time periods tested (0–1, 1–2, 2–3 h). In addition, the IGF decrease the quantity of [14C]leucine protein eluted at the position of labelled rat GH on Sephadex G75, which would include newly synthesized GH extracted from the cells. Thus we conclude that the decreased GH released may be due to an effect of IGF on both rate of release and on GH synthesis.

scholarly journals Cortistatin mimics somatostatin by inducing a dual, dose-dependent stimulatory and inhibitory effect on growth hormone secretion in somatotropes

2006 ◽  
Vol 36 (3) ◽  
pp. 547-556 ◽  
Author(s):  
R M Luque ◽  
J R Peinado ◽  
F Gracia-Navarro ◽  
F Broglio ◽  
E Ghigo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Binding Capacity ◽  
Short Form ◽  
Hormone Secretion ◽  
Somatostatin Receptors ◽  
Growth Hormone Secretion ◽  
Full Length ◽  
Gh Secretion ◽  
Dose Dependent

Cortistatin is a recently discovered neuropeptide that is structurally related to somatostatin, the classic inhibitor of growth hormone (GH) release. Cortistatin binds with high affinity to all five somatostatin receptors (sst1–5), and, like somatostatin, cortistatin inhibits in vivo GH release in man and rats. In this report, we compared the in vitro actions of cortistatin and somatostatin using primary pig pituitary cell cultures. In this species, we have previously reported that somatostatin not only inhibits GH-releasing hormone (GHRH)-stimulated GH release at high doses, but also stimulates basal GH release at low (pM) doses, a dual response that is markedly dependent on the subpopulation of pituitary somatotropes examined. Results reported herein demonstrate that cortistatin closely mimics the dose-dependent inhibitory and stimulatory effects of somatostatin on GH secretion. As cortistatin, unlike somatostatin, binds to the human receptor for ghrelin/GH secretagogs (GHS-R), we also investigated whether cortistatin stimulates GH release through this receptor by using a synthetic, short form of cortistatin, cortistatin-8 (CST8), which lacks the sst-binding capacity of full-length cortistatin but retains its GHS-R-binding capacity. Interestingly, CST8 stimulated GH release only at low doses (10−15 M), and did not reduce GH secretion stimulated by GHRH, ghrelin, or low-dose, full-length cortistatin, yet it counteracted that induced by a nonpeptidyl GHS, L-163 255. Taken together, our results indicate that the dual, inhibitory and stimulatory effects of cortistatin on GH release closely parallel those of somatostatin and are probably mediated by the same receptor(s) and signaling pathway(s) for both peptides. Furthermore, they suggest that the pathway(s) activated by cortistatin (and somatostatin) to stimulate GH release are not initiated by GHS-R activation.

Thyroidal inhibition of growth hormone secretion in fowl: tri-iodothyronine-induced down-regulation of thyrotrophin-releasing hormone-binding sites on pituitary membranes

1990 ◽  
Vol 4 (2) ◽  
pp. 127-134 ◽  
Author(s):  
S. Harvey ◽  
J. S. Baidwan
Keyword(s):  
Binding Sites ◽  
Plasma Membranes ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Down Regulation ◽  
Thyrotrophin Releasing Hormone ◽  
Caudal Lobe ◽  
Gh Secretion

ABSTRACT The number, but not affinity, of binding sites for [3H]3-methyl-histidine2-TRH ([3H]Me-TRH) on chicken adenohypophysial plasma membranes was increased in chickens made hypothyroid by goitrogen (methimazole) treatment (50 mg/kg per day for 7 days), which also increased circulating GH concentrations. Daily i.p. injection of thyroxine (T4; 100 μg/kg for 7 days) had no effect on [3H]Me-TRH binding to pituitary membranes, although it suppressed endogenous GH secretion. Binding of [3H]Me-TRH to pituitary caudal lobe membranes was, however, suppressed by tri-iodothyronine (T3) injected chronically (100 μg/kg per day, i.p., for 7 days) or acutely (100 μg/kg, 2 h before being killed). The suppression of [3H]Me-TRH binding and inhibition of GH secretion following T3 administration was dose related. Binding of [3H]Me-TRH to caudal lobe membranes was also suppressed following the incubation of pituitary glands with T3 in vitro, and the response was both dose and time related. These results suggest that T3 inhibits GH secretion in fowl by a down-regulation of pituitary TRH receptors. However, other mechanisms are involved in thyroidal inhibition of GH release in birds, since T4 had no effects on [3H]Me-TRH binding yet suppressed GH secretion in vivo.

scholarly journals Involvement of the Sst1 Somatostatin Receptor Subtype in the Intrahypothalamic Neuronal Network Regulating Growth Hormone Secretion: Anin Vitroandin VivoAntisense Study1

Endocrinology ◽  
2000 ◽  
Vol 141 (3) ◽  
pp. 967-979 ◽  
Author(s):  
Christophe Lanneau ◽  
Marie Thérèse Bluet-Pajot ◽  
Philippe Zizzari ◽  
Zsolt Csaba ◽  
Pascal Dournaud ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Neuronal Network ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Receptor Subtype

Interleukin-2 Transiently Inhibits Pulsatile Growth Hormone Secretion in Young but not Older Healthy Men

2021 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Rebecca Yang ◽  
Johannes D Veldhuis
Keyword(s):  
Hormone Secretion ◽  
Interleukin 2 ◽  
Age Groups ◽  
Growth Hormone Secretion ◽  
Experimental Conditions ◽  
Deconvolution Analysis ◽  
Healthy Men ◽  
Gh Secretion ◽  
Older Subjects ◽  
Young Subjects

Abstract Context Interleukin-2 (IL2), a proinflammatory cytokine, has been used to treat malignancies. Increased cortisol and ACTH were noted, but GH secretion was not investigated in detail. Objective We quantified GH secretion after a single sc injection of IL2 in 17 young and 18 older healthy men in relation to dose, age and body composition. Design This was a placebo-controlled, blinded, prospectively randomized cross-over study. At 20:00 h IL2 (3 or 6 million units per m2 ) or saline was injected sc. Lights were off between 23:00 and 07:00 h. Blood was sampled at 10-min intervals for 24 h. Outcome measures Deconvolution analysis of GH secretion. Results GH profiles were pulsatile under both experimental conditions and lower in older than young volunteers. Since the effect of IL2 might be time-limited, GH analyses were performed on the complete 24-h series and the 6 h after IL2 administration. Total and pulsatile 24-h GH secretion decreased nonsignificantly. Pulsatile secretion fell over the first 6 h after IL2 (P=0.034), with visceral fat as covariate (P=0.003), but not age(P=0.10). Plots of cumulative 2-h bins of GH pulse mass showed a distinction by treatment and age groups: a temporary GH decrease of 32% and 28% occurred in the first 2-h bins after midnight (P=0.019 and 0.038) in young subjects, while in older subjects no differences were present at any time point. Conclusion This study demonstrates that IL2 temporarily diminishes GH secretion in young, but not elderly, men.

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