Antagonism by Cortisone of the Linear Growth Induced in Hypopituitary Patients and Hypophysectomized Rats by Human Growth Hormone1

Soyka, Lester F.; Crawford, John D.

doi:10.1210/jcem-25-4-469

Cited by 67 publications

(20 citation statements)

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“…The every-other-day regimen could allow more normal GH production during part of the 48 hr period. or the inhibition to the peripheral action of GH (30) could be decreased during part of the 48 hr. Three of the five women studied before and during every-otherday prednisone therapy had little change in ICGH and io decrease of GH production on the day of prednisone (Fig.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone: Metabolic Clearance Rates, Integrated Concentrations, and Production Rates in Normal Adults and the Effect of Prednisone

Thompson¹,

Rodríguez²,

Kowarski³

et al. 1972

J. Clin. Invest.

130

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A B S T R A C T A constant withdrawal pump was used to determine the integrated concentration of growth hormone (ICGH) which was used in conjunction with the metabolic clearance rate (MCR) of growth hormone (GH) to calculate the GH production rates (GHPR) in normal adults, acromegalics, and normal controls receiving prednisone.The mean ICGH for 22 premenopausal females on no medication was 3.0±1.6 ng/ml (SD) which is significantly lower (P < 0.005) than the mean of 6.6±2.9 for 10 women receiving oral contraceptives and significantly higher than the means of 1.5±0.75 for 5 postmenopausal females (P < 0.05) and 1.8±1.0 for 16 adult males (P < 0.01) which are comparable. The mean GHPR's in mg/24 hr per m' for the four groups are: normal females 0.52±0.24 (SD), females receiving contraceptive pills 1.65±0.58 (P < 0.005), postmenopausal females = 0.26±0.12 (P < 0.025), and adult males 0.35±0.23 (P < 0.025).Three untreated acromegalic patients had ICGH's of 59, 82, and 93 ng/ml and GHPR's ranging from 14.5 to 17.9 mg/24 hr.Prednisone in a dose of 20 mg t.i.d. for 8 days significantly decreased both the ICGH and GHPR. Alternate day prednisone (60 mg in a single q.o.d. dose) resulted in less consistent inhibition of GH -release which may play a role in the more normal growth seen in children receiving q.o.d. prednisone.

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Section: Discussionmentioning

confidence: 99%

Growth Hormone: Metabolic Clearance Rates, Integrated Concentrations, and Production Rates in Normal Adults and the Effect of Prednisone

Thompson¹,

Rodríguez²,

Kowarski³

et al. 1972

J. Clin. Invest.

130

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“…In rats, although corticosteroids increase the amount of growth hormone in the pituitary, growth hormone release after insulin hypoglycaemia is impaired (22) and there may be peripheral antagonism of the effects of growth hormone by corticosteroids (28). The results we obtained might have been different with other corticosteroids, alternative dosage schedules, or a different duration or timing of treatment.…”

Section: Discussionmentioning

confidence: 64%

Catch-up Growth in Cortisone–Treated Rats: Effects of Calcium and Vitamin D

1978

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SummaryThe aim of the study was to develop an animal model of steroid stunting and catch-up growth and to investigate the possibility that calcium supplements, with or without vitamin D supplements, might mitigate the effects of corticosteroids on linear growth.In the first experiment, newly weaned Wistar rats were allocated to four groups and weight and tail length measured weekly. In three groups cortisone was injected daily for 28 days. Two of the cortisone-treated groups were given calfium supplekents daily in different dosage schedules. During cortisone treatment (Table I), animals given cortisone gained less weight than the controls ( P < 0.01). After cortisone was stopped the groups previously given cortisone showed greater weight gain than the controls ( P < 0.01). Changes in tail length (Fig. 2), representing changes in linear growth, showed that groups receiving cortisone grew less than the controls during cortisone treatment. After cortisone was stopped the control group grew less than the three groups that had previously received cortisone. There was no beneficial effect of supplemental calcium on either the degree of growth retardation or of catch-up growth (Tables 1 and 2).A second experiment was performed to test the reproducibility of the method and to study the effects of calcium and vitamin D supplements on growth. Newly weaned rats were allocated to four groups. Three groups received cortisone for 42 days. Two of the cortisone-treated groups received vitamin D once a week and one of these groups received calcium supplements. Weight and tail length velocities (Figs. 5 and 6) show less velocity than that of the cortisone-treated groups during cortisone treatment, and after cortisone was stopped the control group had lesser velocity. During cortisone treatment (Table 3), the control groups gained more weight than the three groups given cortisone ( P < 0.001). After cortisone was stopped the groups previously receiving cortisone gained more weight than the control group ( P < 0.01 for cortisone alone and P < 0.001 for cortisone and vitamin D). Changes in mean tail lengths (Table 4) show that during cortisone treatment the three groups given cortisone alone, cortisone and vitamin D, and cortisone, vitamin D, and calcium, all gained less than the controls ( P < 0.001). After cortisone was stopped the groups previously treated with cortisone had a greater increase in tail length than the control groups (P < 0.001). The group given vitamin D supplements grew more than the group given cortisone without such supplements (P < 0.01). The food consumed by the animals (g/100 g body wt/day) was measured ( Fig. 7), and at no time did the control group eat more than the cortisone-treated groups. Reduced calorie intake was not the explanation for retardation of growth, and the increased food intake after cortisone was presumably necessary for catch-up. The serum calcium and total body calcium at the end of the experiment (Table 5) did not suggest that cortisone had depleted the skeleton of calcium.The experimen...

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“…The greater effect of HGH injected at 11 p.m. was usually evident in the retentions of N and P, less often in those of Na and K. The results of series I are summarized in Tables III and IV (30); HGH injected at bedtime will promote mobilization of free fatty acids during the fasting hours of the night, while this effect after matinal injection will be inhibited by the diurnal food intake (30). (c) The anabolic action of HGH, which is opposed by cortisol (25,26), may be greater after nocturnal injection because the hormone reaches its target tissues during a period when cortisol concentration in extracellular fluids is low.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, secretion of cortisol, which antagonizes the anabolic effect of HGH (25,26), shows the opposite rhythm. Although this hormone is secreted episodically (27), its plasma concentration is greater during the day than at night (28,29).…”

mentioning

confidence: 99%

Diurnal Variation in the Responsiveness of Human Subjects to Human Growth Hormone

Rudman¹,

Freides²,

Patterson³

et al. 1973

J. Clin. Invest.

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A B S T R A C T The objective of this study was to compare the responsiveness of human subjects to the anabolic effects of human growth hormone (HGH) administered at 8 a.m. or at 11 p.m. Three doses of HGH were used: A, 0.0168 U/kg body weight (BW)"'4 per day; B, 0.0532 U/kg BW"/' per day; C, 0.168 U/kg BW"'4 per day. The effect of each dose on daily balances of N, P, Na, and K and on BW was measured. The subjects were of two groups: (a) seven GH-deficient children, of whom three were deficient in ACTH; and (b) three patients with limb-girdle dystrophy. ACTHdeficient patients in group (a) received exogenous cortisol at 7 a.m. In all 10 subjects, the anabolic effects of dose C, and sometimes of B and A, administered at 11 p.m. were significantly (P < 0.05) greater than when administered at 8 a.m. In these experiments plasma cortisol concentration averaged 3 times greater at 8 a.m. than at 11 p.m.In the next experiments, exogenous cortisol was administered to the three ACTH-deficient patients at 10 p.m. and the responsiveness to HGH injected at 11 p.m. vs. 8 a.m. was again compared. Under these conditions, when plasma cortisol concentration averaged 3 times greater at 11 p.m. than at 8 a.m., HGH injected at 8 a.m. caused significantly greater anabolic responses than HGH injected at 11 p.m.These findings indicate that the magnitude of the anabolic response to exogenous HGH is inversely related to the plasma cortisol concentration at the time of HGH injection.

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Antagonism by Cortisone of the Linear Growth Induced in Hypopituitary Patients and Hypophysectomized Rats by Human Growth Hormone1

Cited by 67 publications

References 0 publications

Growth Hormone: Metabolic Clearance Rates, Integrated Concentrations, and Production Rates in Normal Adults and the Effect of Prednisone

Growth Hormone: Metabolic Clearance Rates, Integrated Concentrations, and Production Rates in Normal Adults and the Effect of Prednisone

Catch-up Growth in Cortisone–Treated Rats: Effects of Calcium and Vitamin D

Diurnal Variation in the Responsiveness of Human Subjects to Human Growth Hormone

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