Growth hormone (GH) secretion in the conscious rat: negative feedback of GH on its own release

1988 ◽  
Vol 119 (2) ◽  
pp. 201-209 ◽  
Author(s):  
R. G. Clark ◽  
L. M. S. Carlsson ◽  
I. C. A. F. Robinson

ABSTRACT The negative-feedback effects of GH on its own secretion were studied in conscious male and female rats bearing indwelling double-bore venous cannulae. Intravenous infusions of human GH (hGH; 20–60 μg/h) or somatostatin (SS; 10 μg/h) were given while frequent serial microsamples of blood were withdrawn using an automatic blood-sampling system. In both sexes, i.v. infusions of hGH for 6 h inhibited endogenous GH secretory pulses, with a slow onset of the inhibition. There was no rebound GH secretion immediately following the removal of the hGH infusion, but spontaneous GH secretion gradually returned to normal. Infusions of hGH did not inhibit the pituitary GH response to repeated GH-releasing factor (GRF) injections (1 μg) given i.v. every 40 min to female rats. By contrast, infusions of SS, which also blocked spontaneous GH release, dramatically reduced the GH responses to serial GRF injections. When SS Infusions were stopped, the subsequent GRF-induced GH secretory responses were enhanced. These results show that GH can inhibit its own release when given by i.v. infusion to conscious male and female rats. Since GH responses to GRF are maintained during a GH infusion, the feedback effect of GH is unlikely to be exerted directly on the pituitary or by increasing SS release. Our results are consistent with the idea that GH feedback in the conscious rat involves an inhibition of GRF release. J. Endocr. (1988) 119, 201–209

1990 ◽  
Vol 126 (1) ◽  
pp. 27-35 ◽  
Author(s):  
L. M. S. Carlsson ◽  
R. G. Clark ◽  
I. C. A. F. Robinson

ABSTRACT Growth hormone inhibits its own secretion in animals and man but the mechanism for this inhibition is unclear: both stimulation of somatostatin release and inhibition of GH-releasing factor (GRF) release have been implicated. We have now studied the GRF responsiveness of conscious male and female rats under conditions of GH feedback induced by constant infusion of exogenous human GH (hGH). Intravenous infusions of hGH (60 μg/h) were maintained for 3 to 6 h whilst serial injections of GRF(1–29)NH2 (0·2–1 μg) were given at 45-min intervals. The GH responses were studied by assaying blood samples withdrawn at frequent intervals using an automatic blood sampling system. We have confirmed that male and female rats differ in their ability to respond to a series of GRF injections; female rats produced consistent GH responses for up to 13 consecutive GRF injections, whereas male rats showed a 3-hourly pattern of intermittent responsiveness. In female rats, multiple injections of GRF continued to elicit uniform GH responses during hGH infusions, whereas hGH infusions in male rats disturbed their intermittent pattern of responsiveness to GRF, and their regular 3-hourly cycle of refractoriness was prolonged. We suggest that this sex difference in GH feedback may be due to GH altering the pattern of endogenous somatostatin release differentially in male and female rats. Such a mechanism of GH autofeedback could be involved in the physiological control of the sexually differentiated pattern of GH secretion in the rat. Journal of Endocrinology (1990) 126, 27–35


1985 ◽  
Vol 106 (3) ◽  
pp. 281-289 ◽  
Author(s):  
R. G. Clark ◽  
I. C. A. F. Robinson

ABSTRACT The GH responses to single i.v. injections of GH-releasing factor (GRF) in conscious male rats are highly variable. Although normal male rats show a pulsatile secretory pattern of GH with pulses occurring at intervals of 3–3·5 h, the peaks occur at different times in individual animals. We have compared the GH responses of young conscious male and female rats to multiple i.v. injections of 1 μg human (h) GRF1-29NH2. The peak GH responses occurred 3–5 min after hGRF1-29NH2 injection and were lower in female than in male rats. Both males and females responded uniformly to hGRF1-29NH2 injections given 180 min apart and the GH responses became entrained with no endogenous GH pulsing. Female rats produced consistent GH peaks in response to hGRF1-29NH2 injections at 90-min intervals, whereas male rats responded only to alternate injections, so that GH peaks occurred only every 180 min despite giving GRF every 90 min. When the frequency of hGRF1-29NH2 administration was increased to once every 40 min female rats again responded consistently to each injection. Male rats responded intermittently, being able to respond to two injections 40 min apart, after which they became refractory to hGRF1-29NH2. This cycle of varying sensitivity to GRF in male rats probably underlies their 3-hourly endogenous GH secretory rhythm. Female rats can respond uniformly to repeated GRF injections, consistent with their more continuous pattern of endogenous GH secretion. Introducing a pulse of 10 μg rat GH into a series of hGRF1-29NH2 injections did not induce refractoriness to hGRF1-29NH2, suggesting that GH does not itself desensitize the pituitary to GRF. Whether the different patterns of GH secretion in males and females result from different patterns of GRF and/or somatostatin secretion remains to be determined. J. Endocr. (1985) 106, 281–289


1988 ◽  
Vol 119 (3) ◽  
pp. 397-404 ◽  
Author(s):  
R. G. Clark ◽  
L. M. S. Carlsson ◽  
B. Rafferty ◽  
I. C. A. F. Robinson

ABSTRACT We have studied the rebound secretion of GH following short-term somatostatin (SS) infusions in conscious rats, using an automatic sampling system for withdrawing frequent microsamples of blood. Intravenous infusions of SS (5–50 μg/h per rat) inhibited spontaneous GH secretion, but when SS was withdrawn there was a large burst of rebound GH secretion. A sub-anaesthetic dose of urethane reduced such rebound bursts of GH, suggesting a hypothalamic involvement in rebound GH secretion. Passive immunization with an antibody against rat GH-releasing factor (GRF) attenuated the rebound GH secretory response to the withdrawal of an SS infusion (GH concentration during rebound secretion was 26±21 μg/l vs 475 ± 127 μg/l (mean ± s.e.m.), after 0·5 ml anti-GRF serum or non-immune serum respectively). The inhibition of GH rebound secretion was related to the dose of anti-GRF serum administered. Intravenous infusions of human GH (20– 100 μg/h per rat) also reduced the size of the rebound GH secretion following SS withdrawal, in both male and female rats. We suggest that the rebound GH secretion that follows SS withdrawal in vivo is caused mainly by a hypothalamic release of GRF. Exogenous GH inhibits SS-induced rebound GH secretion in the conscious rat, possibly by inhibiting hypothalamic GRF release. J. Endocr. (1988) 119, 397–404


1968 ◽  
Vol 58 (4) ◽  
pp. 600-612 ◽  
Author(s):  
Robert Boyd ◽  
Donald C. Johnson

ABSTRACT The effects of various doses of testosterone propionate (TP) upon the release of luteinizing hormone (LH or ICSH) from the hypophysis of a gonadectomized male or female rat were compared. Prostate weight in hypophysectomized male parabiotic partners was used to evaluate the quantity of circulating LH. Hypophyseal LH was measured by the ovarian ascorbic acid depletion method. Males castrated when 45 days old secreted significantly more LH and had three times the amount of pituitary LH as ovariectomized females. Administration of 25 μg TP daily reduced the amount of LH in the plasma, and increased the amount in the pituitary gland, in both sexes. Treatment with 50 μg caused a further reduction in plasma LH in males, but not in females, while pituitary levels in both were equal to that of their respective controls. LH fell to the same low level in partners of males or females receiving 100 μg TP. When gonadectomized at 39 days, males and females had the same amount of plasma LH, but males had more stored hormone. Pituitary levels were unchanged from controls following treatment with 12.5, 25 or 50 μg TP daily, but plasma values dropped an equal amount in both sexes with the latter two doses. Androgenized males or females, gonadectomized when 39 days old, were very sensitive to the effects of TP and plasma LH was significantly reduced with 12.5 μg daily. Pituitary LH in androgenized males was higher than that of normal males but was reduced to normal by small amounts of TP. The amount of stored LH in androgenized females was not different from that of normal females and it was unchanged by any dose of TP tested. Results are consistent with the conclusion that the male hypothalamic-hypophyseal axis is at least as sensitive as the female axis to the negative feedback effects of TP. Androgenization increases the sensitivity to TP in both males and females.


Physiology ◽  
1986 ◽  
Vol 1 (2) ◽  
pp. 44-47
Author(s):  
OGP Isakkson ◽  
J-O Jansson ◽  
RG Clark ◽  
I Robinson

The plasma concentration of growth hormone fluctuates widely with pronounced peaks at intervals of a few hours and troughs of nearly vanishingly low concentrations in between. The pattern of secretion varies, and different patterns affect growth differently. Tall children usually have frequent growth hormone peaks of a high amplitude, whereas short, healthy children usually have fewer peaks of a lower amplitude. Male and female rats have different patterns, and a "masculine" pattern promotes growth more than a "feminine" pattern. If the same amount of growth hormone is administered in several pulses rather than continuously, the effect on growth is much greater.


1986 ◽  
Vol 372 (2) ◽  
pp. 361-365 ◽  
Author(s):  
Ichiji Wakabayashi ◽  
Hisaaki Hatano ◽  
Shiro Minami ◽  
Yoji Tonegawa ◽  
Shigeo Akira ◽  
...  

Endocrinology ◽  
1995 ◽  
Vol 136 (6) ◽  
pp. 2664-2670 ◽  
Author(s):  
J A Butkus ◽  
R S Brogan ◽  
A Giustina ◽  
G Kastello ◽  
M Sothmann ◽  
...  

1977 ◽  
Vol 6 (s1) ◽  
pp. 19-28 ◽  
Author(s):  
LEON C. TERRY ◽  
ADAH SAUNDERS ◽  
JUDY AUDET ◽  
JOHN O. WILLOUGHBY ◽  
PAUL BRAZEAU ◽  
...  

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