Thyrotrophin-releasing hormone-induced growth hormone (GH) secretion in anaesthetized chickens: inhibition by GH-releasing factor at central sites

1991 ◽  
Vol 128 (1) ◽  
pp. 13-19 ◽  
Author(s):  
C. A. Ahene ◽  
R. W. Lea ◽  
S. Harvey

ABSTRACT Intracerebroventricular (i.c.v.) administration of GH-releasing factor (GRF) (at 1 or 10 μg) to anaesthetized immature (6- to 8-weeks-old) or adult (> 24-weeks-old) domestic fowl had no effect on basal GH concentrations in peripheral plasma, but suppressed (after 20 min) the acute GH response to exogenous (i.v.) thyrotrophin-releasing hormone (TRH) (1 μg/kg). The i.c.v. injection of GRF also reduced the content of somatostatin (SRIF) and dopamine (DA) in the hypothalamus, while increasing the concentration of the DA metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) and the DOPAC/DA ratio. The release of SRIF from hypothalamic tissue was stimulated in vitro by 100 nmol GRF/l. The inhibitory effect of i.c.v. GRF on TRH-induced GH secretion was blocked when it was simultaneously injected i.c.v. with SRIF antiserum. These results demonstrate central effects of GRF on avian hypothalamic function and suggest an inhibitory role for this peptide in GH regulation, possibly mediated through increased SRIF secretion. Journal of Endocrinology (1991) 128, 13–19

1993 ◽  
Vol 138 (1) ◽  
pp. 137-147 ◽  
Author(s):  
S. Harvey ◽  
V. L. Trudeau ◽  
R. J. Ashworth ◽  
S. M. Cockle

ABSTRACT Pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2) is a tripeptide with structural and immunological similarities to thyrotrophin-releasing hormone (TRH; pGlu-His-ProNH2). Since TRH stimulates GH secretion in domestic fowl, the possibility that pGlu-Glu-ProNH2 may also provoke GH release was investigated. Unlike TRH, pGlu-Glu-ProNH2 alone had no effect on GH release from incubated chicken pituitary glands and did not down-regulate pituitary TRH receptors. However, pGlu-Glu-ProNH2 suppressed TRH-induced GH release from pituitary glands incubated in vitro and competitively displaced [3H]methyl3-histidine2-TRH from pituitary membranes. Systemic injections of pGlu-Glu-ProNH2 had no significant effect on basal GH concentrations in conscious birds, but promptly lowered circulating GH levels in sodiumpentobarbitone anaesthetized fowl. Submaximal GH responses of conscious and anaesthetized birds to systemic TRH challenge were, however, potentiated by prior or concomitant administration of pGlu-Glu-ProNH2. These results demonstrate, for the first time, that pGlu-Glu-ProNH2 has biological activity, with inhibitory and stimulatory actions within the avian hypothalamo-pituitary axis. These results indicate that pGlu-Glu-ProNH2 may act as a TRH receptor antagonist within this axis. Journal of Endocrinology (1993) 138, 137–147


1981 ◽  
Vol 97 (4) ◽  
pp. 448-453 ◽  
Author(s):  
C. G. Scanes ◽  
S. Harvey ◽  
B. A. Morgan ◽  
M. Hayes

Abstract. Variations in plasma growth hormone (GH) concentrations following iv or sc administration of synthetic thyrotrophin-releasing hormone (TRH, Pyr-His-Pro-NH2) have been followed in immature and adult domestic fowl. TRH markedly stimulated GH secretion in newly hatched (1 and 2 day old) chicks and in 6-week-old cockerels but in adult male or female birds of two strains had very little effect, if any. Intravenous injection of 4 TRH analogues (Pyr-His-Mep-NH2, Pyr-Meh-Mep-NH2, Pyr-Meh-Mep-NH and Pyr-Meh-Pro-NH2) were also potent GH secretagogues in 6-week-old birds. The stimulatory effect of TRH or the TRH-analogues on GH secretion was not dose-related.


1990 ◽  
Vol 126 (1) ◽  
pp. 83-88 ◽  
Author(s):  
S. Harvey ◽  
R. W. Lea ◽  
C. Ahene

ABSTRACT Peripheral plasma concentrations of GH in adult chickens were increased, in a dose-related manner, between 5 and 30 min after the intracerebroventricular (i.c.v.) injection of 0·1 or 10 μg TRH. In contrast, i.v. administration of comparable doses of TRH had no significant effect on circulating GH concentrations. [3H]3-methyl-histidine2-TRH ([3H]Me-TRH) was located in the pituitary gland and peripheral plasma within 5 min of its i.c.v. administration, although in amounts that were unlikely to affect directly pituitary function. [3H]Me-TRH rapidly accumulated in the hypothalamus following its i.c.v. administration (but not after i.v. injection), and the central effect of TRH on GH secretion in birds is therefore likely to be induced by effects at hypothalamic sites. Journal of Endocrinology (1990) 126, 83–88


1985 ◽  
Vol 105 (3) ◽  
pp. 351-355 ◽  
Author(s):  
H. Klandorf ◽  
S. Harvey ◽  
H. M. Fraser

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


1990 ◽  
Vol 126 (1) ◽  
pp. 75-81 ◽  
Author(s):  
S. Harvey

ABSTRACT Tri-iodothyronine (T3) had no effect on the basal level of GH release from chicken hemipituitary glands perifused in vitro. The GH response to TRH was, however, markedly suppressed following exposure to T3. Suppression of TRH-stimulated GH secretion was observed after a 2-h preincubation with T3, and was induced, in a dose-related way, by 0·01–10 μmol T3/l. Exposure to T3 also reduced the effectiveness of TRH, at concentrations of 0·001–10 μg/ml, to stimulate GH release. These results demonstrate that, in addition to a hypothalamic site of action, T3 is likely to suppress GH secretion in vivo by direct effects on pituitary GH release. Journal of Endocrinology (1990) 126, 75–81


1991 ◽  
Vol 131 (1) ◽  
pp. 39-48 ◽  
Author(s):  
R. J. Denver ◽  
S. Harvey

ABSTRACT Hypothyroidism reduces GH synthesis and release in several mammalian species, in which thyroid hormone directly stimulates GH gene transcription. In contrast, hypothyroidism stimulates GH secretion in birds, in which thyroid hormone directly inhibits pituitary GH release. We have, therefore, investigated the effects of thyroid status on the accumulation of newly synthesized GH in the pituitaries of 8- to 10-week-old Leghorn cockerels in vitro and in vivo. The incorporation of [35S]methionine into immunoprecipitable GH ([35S] GH) was increased, over a 4-h incubation period, in glands from birds made hypothyroid by injections of methimazole (50 mg/kg day for 10 days) in comparison with glands from vehicle-injected controls. Treatment with tri-iodothyronine (T3, 100 μg/kg per day for 10 days) in vivo did not significantly alter the accumulation of [35S]GH in vitro but did block the release of [35S]GH in response to a GH secretagogue (thyrotrophin-releasing hormone; exposure to 280 nmol/l for 30 min) and reduced immunoassayable pituitary GH content. Pretreatment of glands from euthyroid birds with T3 (100 nmol/l) in vitro (for 20 h) reduced the basal accumulation of [35S]GH as well as that induced by another GH secretagogue (GH-releasing factor; 100 nmol/l) during a 6-h labelling period. These results show that, unlike the generally stimulatory action of thyroid hormone in mammals, in birds, T3 exerts a direct inhibitory effect on the accumulation of newly synthesized pituitary GH. Journal of Endocrinology (1991) 131, 39–48


1981 ◽  
Vol 89 (3) ◽  
pp. 405-410 ◽  
Author(s):  
S. HARVEY ◽  
R. J. STERLING ◽  
J. G. PHILLIPS

Age-related changes in the response of GH to administration of thyrotrophin releasing hormone (TRH) have been investigated in the domestic fowl. In two strains of chicken the i.v. administration of TRH (10 μg/kg) to 4-week-old male and female birds markedly increased (> 200 ng/ml) the plasma GH concentration within 10 min of treatment and the concentration remained higher than the pretreatment level for at least a further 20 min. Saline (0·9%) administration had no effect on GH secretion in comparable groups of control birds. The same dose of TRH had no effect on plasma GH concentrations in adult (> 24-week-old) laying hens or cockerels. The administration of TRH at doses of 0·1–100 μg/kg (i.v.) or 0·39–50 μg/bird (s.c.) also had very little, if any, effect on GH secretion in laying hens. In laying hens slight increases (10–20 ng/ml, P < 0·05) in the plasma concentrations of GH were observed in one experiment 60 min after the s.c. injection of 100 μg TRH, and in another 60, 90 and 120 min after the serial s.c. injection of TRH (100 μg/bird) every 30 min over a 150 min period. The poor GH response of the adults to TRH stimulation was not due to high circulating concentrations of endogenous gonadal steroids, as surgical gonadectomy had no effect on the GH response to TRH. These results suggest maturational differences in the control of GH secretion in the fowl.


1984 ◽  
Vol 105 (2) ◽  
pp. 156-160 ◽  
Author(s):  
R. D. Askew ◽  
D. B. Ramsden ◽  
M. C. Sheppard

Abstract. The effects of neurotensin on thyrotrophin (TSH) and prolactin (Prl) release were studied in two in vitro systems – anterior pituitary cells in culture and perifused anterior pituitary fragments. Neurotensin significantly reduced basal secretion of both TSH and Prl (P < 0.001) from cultured pituitary cells, and abolished thyrotrophin releasing hormone (TRH)-stimulated TSH release. Neurotensin significantly reduced TRH-stimulated TSH and Prl release (P < 0.02) from perifused pituitary fragments. These data indicate that neurotensin has a direct inhibitory effect on TSH and Prl secretion by the anterior pituitary.


1993 ◽  
Vol 137 (1) ◽  
pp. 35-42 ◽  
Author(s):  
S. Harvey

ABSTRACT Benzodiazepines are pharmacological agents widely used for their anxiolytic and anticonvulsant properties. However, as these drugs are known to antagonize the binding and action of thyrotrophin-releasing hormone (TRH) in pituitary tissue, the possibility that they may modulate GH secretion was investigated in domestic fowl, in which TRH is a GH-releasing factor. Chlordiazepoxide (an antagonist of central-type benzodiazepine receptors) had no significant effect on the basal release of GH from incubated chicken pituitary glands, but at concentrations > 10 μmol/l chlordiazepoxide suppressed somatotroph responsiveness and sensitivity to TRH stimulation. At this concentration, chlordiazepoxide competitively displaced the binding of [3H]3-methyl-histidine2-TRH ([3H]Me-TRH) to chicken pituitary membranes. The prior incubation of pituitary glands with chlordiazepoxide had no significant effect on the number of [3H]Me-TRH-binding sites, which were also unaffected by the administration of chlordiazepoxide in vivo. However, contrary to its effects in vitro, chlordiazepoxide reduced basal GH secretion in vivo, whilst potentiating the GH response to systemic TRH challenge. These results demonstrate benzodiazepine antagonism of TRH-binding sites in domestic fowl and a biphasic modulation of GH secretion, which may be mediated through opposing actions at pituitary and central sites. Journal of Endocrinology (1993) 137, 35–42


1990 ◽  
Vol 4 (1) ◽  
pp. 13-21 ◽  
Author(s):  
S. Harvey ◽  
J. S. Baidwan

ABSTRACT Administration of ovine GH to immature domestic fowl blunted their subsequent GH response to thyrotrophin-releasing hormone (TRH), a GH secretagogue in birds. The in-vivo administration of GH also reduced the ability of radiolabelled TRH to bind to plasma membranes of the pituitary caudal lobe, in which GH cells predominate. These inhibitory effects of GH were mediated by extrapituitary actions, since GH had no direct inhibitory effects on TRH-induced GH release or on pituitary TRH binding in vitro. GH inhibition of GH secretion and TRH binding would not appear to be mediated by hypothalamic somatostatin (SRIF) or peripheral somatomedin (IGF-I), since SRIF and IGF-I had no direct effects in vitro.


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