586 Horm. Metab. Res. 11 (1979) 586 -587
Circadian Variation of Somatomedin and Cortisol in Pigs G.S.G. Spencer A.R.C. Meat Research Institute, Langford, Bristol, United Kingdom
There are a few recent reports on circadian variation of somatomedin activity in man (Minuto, Grimaldi, Giusti, &iardi, Cocco and Giordano 1978; Preece, Taylor, Holder and Doggett 1978) but there are no such reports for domestic .and laboratory species.
Somatomedin was measured using a porcine eostal cartilage bioassay (Spencer and Taylor 1978) and cortisol by a competitivc protein-binding assay (Radioehemical Centre).
The suggestion that cortisol is an inhibitor of the somatomedin bioassay is unresolved and it is therefore particularly pertinent to measure the associated levels of somatomedin and cortisol in the plasma. This study reports simultaneous levels of somatomedin and cortisol in pigs throughout a 24 ho ur period.
Somatomedin aetivity showed a signifieant eircadian variation with the minimum level oeeuring at 0300 hand the maximum level oeeuring at midday. Plasma cortisol showed two peaks, one at about 0300 hand the other at 1500 h (Figure 1).
Results
Six male pigs with a mean live weight of S4 kg (45 - 71 kg) were studied. lndwelling Teflon catheters were placed in the vena cava via an extern al branch of the jugular vein, while the pigs were under general anaesthesia. After eatheterization the pigs were placed in individual metabolism erates for the duration of the experiment. Each animal was allowed at least five days to reeover from the operation before the start of the experiment. During this time the animals became accustomed to the collection procedure and eollections could be made without subjeeting the an im als to any obvious stress. During the 24 hours eollection period food was withheld but water was allowed ad libitum. The colleetion commenced at 2000 h with the last feeding at 1600 h. Blood was eollected into heparinized tubes at hourly intervais. The blood was centrifuged immediately and the plasma stored at -20°C until analyzed. The period of dark was from 2400 h to 0700 h the following day during which time the minimum light required for colleetion was maintained. During the whole of the experiment stressful stimuli were kept to aminimum.
Somatomedins are growth hormone dependent peptides; hypophyseetomy reduces plasma somatomedin aetivity while administration of growth hormone produces a rise in somatomedin aetivity after eight hours (Takano, Hizuke, Shizume and HaU 1977). As the night peak in growth hormone seeretion in humans oeeurs at 0100 h (Minuto et al. 1978) it might be expeeted that the rise in somatomedin aetivity would oeeur at about 0900 h; this does not appear to be the ease in either humans (Minuto et al. 1978; Preece et al. 1978) or pigs (as reported here) both of wh ich show changing somatomedin levels at approximately the same time of day. Whipp, Wood and Lyon (1970) suggested that the circadian rhythm of cortisol in pigs is similar to that seen in man, although the levels of eortisol in pigs were much lower. However, in that study eortisol concentrations were measured only three times in the day. The bi-phasie pattern of cortisol secretion found in this study, with two peaks of seeretion, approximately 12 hours apart, is consistenl with data wh ich have been previously reported in shecp (HoUey, Beckman and Evans 1975) and pigs (Bottoms, Roesel, Rausch and Akins 1972).
2.0
40.0 1.5
30.0
>
g 1.0 GI
& c:
20.0
~
§0.5
"' E
Jl
0000
0600
1200
1800
Received: S March 1979
Accepted: IS June 1979
0018-5043/79
S 03.00
1032-0586
© 1979
Georg Th ieme Publ ishers
Fig. 1 Somatomedin activity (x---x) and eortisol concentration (- - - - - -) in six pigs at each hour of the day. The values shown are a moving point average (n = 3) of the mean value at each point
Downloaded by: Universite Laval. Copyrighted material.
Discussion
Materials and Methods
Correlation of Calcium and Acid-Base Metabolism The suggestion that the higher afternoon values of somatomedin activity resuIt from a decrease in inhibition of the somatomedin bioassay by cortisol (Van den Brande, Van Buul, Heinrich, Van Roon, Zurcher and Van Steirtegem 1975) are not supported by the findings of this study where cortisol and somatomedin both increase from 0900 hand both have high values between 1200 and 1400 h. Furthermore, as there is a single peak 01' somatomedin activity but two peaks in cortisol secretion, it would appear that increased plasma cortisol does not produce a decrease in somatomedin production. It would thus appear that the observed cireadian variation of somatomedin activity is independent of cortisol secretion.
References Bottoms, G.D., O.F. Roesel, F.D. Rausch, E.L. Akins: Amer. J. Veto Res. 33: 785-790 (1972)
587
Holley, D.C., D.A. Beckman, J. W. Evans: 1. Endocr. 65: 147-148 (1975) Minuto, F., P. Grimaldi, M. Giusti, M. Baiardi, R. Cocco, G. Giordano: Proceedings of an International Symposium on Somatomedins and Growth. Italy (1978) Preece, M.A., A.M. Taylor, A. Holder, P. Daggett: Proceedings of an International Symposium on Somatomedins and Growth. Italy (1978) Spencer, G.S.G., A.M. Taylor: J. Endocr. 78: 83-88 (978) Takano, K., N. Hizuke, K. Shizume, K. Hall: Endocr. Japon. 24: 359-366 (1977) Van den Brande, J.L., S. Van Buul, U. Heinrich, F. Van Roon, T. Zurcher, A.C. Van Steirtegem: Adv. Metab. Disorders 8: 171-181 (1975) Whipp, S.c., R.L. Wood, N.C. Lyon: Amer. J. Veto Res. 31: 2105-2107 (1970)
Horm. Metab. Res. II (1979) 587 588
Correlation of Calcium and Acid-Base Metabolism J. Girndt, H.V. Henning and G. Delling Medizinische Universitätsklinik, Göttingen end Pathologisches Institut, Universität Hamburg, Germany The physiologic active fraction of calcium in blood is ionized calcium, the proportion of which in respect to total calcium being elevated in metabolie acidosis and lowered in metabolie alkalosis (Girndt, Henning and Fuchs 1979). The following results indicate that the organism tries to normalize the concentration of the ionized calcium in spite of variations in total calcium by changes of the pH of blood. Hy feeding neWborn rats with different diets we were able to induce different concentrations of total plasma calcium, ranging from low to high, in the several groups of animals. The standard bicarbonate of blood showed a paraUel variation to total plasma calcium.
Methods Wistar-strain rats aged 3 weeks and weighing 50 g were kept in dark cages. Two groups of animals were fed the vitaminD-free and phosphate-depleted diet AItromin® C 1017, one group of animals was fed with Altromin® C 1000, the latter containing vitamin D in an amount of 500 I.E./kg and phosphate in an amount of 0.4%. One of the groups of vitamin-D-depleted rats got a restriction 01' calcium by drinking calcium-free water. The other vitamin-D-depleted rats were. drinking water with a high calcium content of 4.7 mval/I. A fourth group of rats was parathyroidectomized before the beginning of the experiment. Rats were fed and handled as described above for six weeks. Following this they were decapitated. The arte rial blood of the carotid artery was used for determination of standard bicarbonate and total calcium content, thc lattcr being measured by flame photometry. Reeeived: 19 Dee. 1978
Accepted: 7 Aug. 1979
0018-5043/79
103.00
1032 -0587
In some animals of the first three groups ionized calcium eould be mcasured. Measurement was done potentiometrieally with the Orion SS 20 apparatus.
Results In vitamin-D- and phosphate-depleted rats severe disturbance of the skeletal mineralisation devclops. It was surprising to find that those rats, drinking water with high calcium content showed high concentrations of total plasma calcium. In addition, these animals showed metabolie alkalosis with high standard bicarbonate concentrations (figure below). Contrary to this, vitamin-D- and phosphate-deplcted rats drinking calcium-free water showed low total plasma calcium concentrations. These animals had low standard bicarbonate concentrations. The following figure correlates standard bicarbonate and total calcium in all experimental animals. There is a significant linear correlation, except in those animals, which were parathyroidcctomizcd. Figure two shows that in those animals, in which ionizcd calcium could be measured, the percentage of this in respect to total calcium was inversely eorrelated to the pH value.
Discussion Thc different calcium coneentrations in plasma in the several groups of animals enabled us to test, whether chronic variations in calcium concentration are followed by variations in acid-base metabolism. As shown in thc first figure, we could indeed dcmonstratc a direel linear correlation between standard bicarbonate and total calcium, which
© 1979 Georg Thieme Publishers
Downloaded by: Universite Laval. Copyrighted material.
Requests for reprints should be addressed to: Dr. G.S.G. Spencer, A.R.C. Meat Research Institute. Langford, Bristol, BSI8 7DY (United Kingdom)
Circadian Variation of Somatomedin and Cortisol in Pigs G.S.G. Spencer A.R.C. Meat Research Institute, Langford, Bristol, United Kingdom
There are a few recent reports on circadian variation of somatomedin activity in man (Minuto, Grimaldi, Giusti, &iardi, Cocco and Giordano 1978; Preece, Taylor, Holder and Doggett 1978) but there are no such reports for domestic .and laboratory species.
Somatomedin was measured using a porcine eostal cartilage bioassay (Spencer and Taylor 1978) and cortisol by a competitivc protein-binding assay (Radioehemical Centre).
The suggestion that cortisol is an inhibitor of the somatomedin bioassay is unresolved and it is therefore particularly pertinent to measure the associated levels of somatomedin and cortisol in the plasma. This study reports simultaneous levels of somatomedin and cortisol in pigs throughout a 24 ho ur period.
Somatomedin aetivity showed a signifieant eircadian variation with the minimum level oeeuring at 0300 hand the maximum level oeeuring at midday. Plasma cortisol showed two peaks, one at about 0300 hand the other at 1500 h (Figure 1).
Results
Six male pigs with a mean live weight of S4 kg (45 - 71 kg) were studied. lndwelling Teflon catheters were placed in the vena cava via an extern al branch of the jugular vein, while the pigs were under general anaesthesia. After eatheterization the pigs were placed in individual metabolism erates for the duration of the experiment. Each animal was allowed at least five days to reeover from the operation before the start of the experiment. During this time the animals became accustomed to the collection procedure and eollections could be made without subjeeting the an im als to any obvious stress. During the 24 hours eollection period food was withheld but water was allowed ad libitum. The colleetion commenced at 2000 h with the last feeding at 1600 h. Blood was eollected into heparinized tubes at hourly intervais. The blood was centrifuged immediately and the plasma stored at -20°C until analyzed. The period of dark was from 2400 h to 0700 h the following day during which time the minimum light required for colleetion was maintained. During the whole of the experiment stressful stimuli were kept to aminimum.
Somatomedins are growth hormone dependent peptides; hypophyseetomy reduces plasma somatomedin aetivity while administration of growth hormone produces a rise in somatomedin aetivity after eight hours (Takano, Hizuke, Shizume and HaU 1977). As the night peak in growth hormone seeretion in humans oeeurs at 0100 h (Minuto et al. 1978) it might be expeeted that the rise in somatomedin aetivity would oeeur at about 0900 h; this does not appear to be the ease in either humans (Minuto et al. 1978; Preece et al. 1978) or pigs (as reported here) both of wh ich show changing somatomedin levels at approximately the same time of day. Whipp, Wood and Lyon (1970) suggested that the circadian rhythm of cortisol in pigs is similar to that seen in man, although the levels of eortisol in pigs were much lower. However, in that study eortisol concentrations were measured only three times in the day. The bi-phasie pattern of cortisol secretion found in this study, with two peaks of seeretion, approximately 12 hours apart, is consistenl with data wh ich have been previously reported in shecp (HoUey, Beckman and Evans 1975) and pigs (Bottoms, Roesel, Rausch and Akins 1972).
2.0
40.0 1.5
30.0
>
g 1.0 GI
& c:
20.0
~
§0.5
"' E
Jl
0000
0600
1200
1800
Received: S March 1979
Accepted: IS June 1979
0018-5043/79
S 03.00
1032-0586
© 1979
Georg Th ieme Publ ishers
Fig. 1 Somatomedin activity (x---x) and eortisol concentration (- - - - - -) in six pigs at each hour of the day. The values shown are a moving point average (n = 3) of the mean value at each point
Downloaded by: Universite Laval. Copyrighted material.
Discussion
Materials and Methods
Correlation of Calcium and Acid-Base Metabolism The suggestion that the higher afternoon values of somatomedin activity resuIt from a decrease in inhibition of the somatomedin bioassay by cortisol (Van den Brande, Van Buul, Heinrich, Van Roon, Zurcher and Van Steirtegem 1975) are not supported by the findings of this study where cortisol and somatomedin both increase from 0900 hand both have high values between 1200 and 1400 h. Furthermore, as there is a single peak 01' somatomedin activity but two peaks in cortisol secretion, it would appear that increased plasma cortisol does not produce a decrease in somatomedin production. It would thus appear that the observed cireadian variation of somatomedin activity is independent of cortisol secretion.
References Bottoms, G.D., O.F. Roesel, F.D. Rausch, E.L. Akins: Amer. J. Veto Res. 33: 785-790 (1972)
587
Holley, D.C., D.A. Beckman, J. W. Evans: 1. Endocr. 65: 147-148 (1975) Minuto, F., P. Grimaldi, M. Giusti, M. Baiardi, R. Cocco, G. Giordano: Proceedings of an International Symposium on Somatomedins and Growth. Italy (1978) Preece, M.A., A.M. Taylor, A. Holder, P. Daggett: Proceedings of an International Symposium on Somatomedins and Growth. Italy (1978) Spencer, G.S.G., A.M. Taylor: J. Endocr. 78: 83-88 (978) Takano, K., N. Hizuke, K. Shizume, K. Hall: Endocr. Japon. 24: 359-366 (1977) Van den Brande, J.L., S. Van Buul, U. Heinrich, F. Van Roon, T. Zurcher, A.C. Van Steirtegem: Adv. Metab. Disorders 8: 171-181 (1975) Whipp, S.c., R.L. Wood, N.C. Lyon: Amer. J. Veto Res. 31: 2105-2107 (1970)
Horm. Metab. Res. II (1979) 587 588
Correlation of Calcium and Acid-Base Metabolism J. Girndt, H.V. Henning and G. Delling Medizinische Universitätsklinik, Göttingen end Pathologisches Institut, Universität Hamburg, Germany The physiologic active fraction of calcium in blood is ionized calcium, the proportion of which in respect to total calcium being elevated in metabolie acidosis and lowered in metabolie alkalosis (Girndt, Henning and Fuchs 1979). The following results indicate that the organism tries to normalize the concentration of the ionized calcium in spite of variations in total calcium by changes of the pH of blood. Hy feeding neWborn rats with different diets we were able to induce different concentrations of total plasma calcium, ranging from low to high, in the several groups of animals. The standard bicarbonate of blood showed a paraUel variation to total plasma calcium.
Methods Wistar-strain rats aged 3 weeks and weighing 50 g were kept in dark cages. Two groups of animals were fed the vitaminD-free and phosphate-depleted diet AItromin® C 1017, one group of animals was fed with Altromin® C 1000, the latter containing vitamin D in an amount of 500 I.E./kg and phosphate in an amount of 0.4%. One of the groups of vitamin-D-depleted rats got a restriction 01' calcium by drinking calcium-free water. The other vitamin-D-depleted rats were. drinking water with a high calcium content of 4.7 mval/I. A fourth group of rats was parathyroidectomized before the beginning of the experiment. Rats were fed and handled as described above for six weeks. Following this they were decapitated. The arte rial blood of the carotid artery was used for determination of standard bicarbonate and total calcium content, thc lattcr being measured by flame photometry. Reeeived: 19 Dee. 1978
Accepted: 7 Aug. 1979
0018-5043/79
103.00
1032 -0587
In some animals of the first three groups ionized calcium eould be mcasured. Measurement was done potentiometrieally with the Orion SS 20 apparatus.
Results In vitamin-D- and phosphate-depleted rats severe disturbance of the skeletal mineralisation devclops. It was surprising to find that those rats, drinking water with high calcium content showed high concentrations of total plasma calcium. In addition, these animals showed metabolie alkalosis with high standard bicarbonate concentrations (figure below). Contrary to this, vitamin-D- and phosphate-deplcted rats drinking calcium-free water showed low total plasma calcium concentrations. These animals had low standard bicarbonate concentrations. The following figure correlates standard bicarbonate and total calcium in all experimental animals. There is a significant linear correlation, except in those animals, which were parathyroidcctomizcd. Figure two shows that in those animals, in which ionizcd calcium could be measured, the percentage of this in respect to total calcium was inversely eorrelated to the pH value.
Discussion Thc different calcium coneentrations in plasma in the several groups of animals enabled us to test, whether chronic variations in calcium concentration are followed by variations in acid-base metabolism. As shown in thc first figure, we could indeed dcmonstratc a direel linear correlation between standard bicarbonate and total calcium, which
© 1979 Georg Thieme Publishers
Downloaded by: Universite Laval. Copyrighted material.
Requests for reprints should be addressed to: Dr. G.S.G. Spencer, A.R.C. Meat Research Institute. Langford, Bristol, BSI8 7DY (United Kingdom)
