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Measurement of the rate of secretion, peripheral metabolism and interconversion of cortisol and cortisone in adult conscious male guinea-pigs
2890
81
MEASUREMENT OF THE RATE OF SECRETION, PERIPHERAL METABOLISM AND INTERCONVERSION OF CORTISOL AND CORTISONE IN AWLT CONSCIOUS MALE GUINEA-PIGS M. Manin, C. Tournaire and P. Delost Laboratoire de Physiologie Animale et ERA CNRS d'Endocrinologie du Developpement Universite de Clermont-Ferrand, Ensemble Scientifique des Cezeaux B.P. 45, 63170 Aubiere, France Received 11-12-81 ABSTRACT Metabolism of the c rtisol (F) and the cortisone (E) was studied by continuous infusion of [P4C]-F and PHI-E in adult conscious male guineapigs. Parameters, calculated from the specific activities of F and E, are expressed in umoles/24 h : production rate of F (PRF) = 8 + 1 and E f;E; ; 44.9 f. 0.7 ; secretion rate of F (QF) = 7.1 t 0.9 aYid E (QE) = ; rate of irreversible metabolism of F (rF) = 6.2 t 0.9 and E (rE)-= i.8 t 0.3 ; percentage of transfer of F into E = 59 t-4% and E into F = 80-t 3%. These results demonstrate that adrenal gland in the adult male giiinea-pig secretes essentially cortisol and little or no cortisone. Practically all the pool of E is derived from transformation of F into E ; the major part of E production is reconverted into F. INTRODUCTION Cortisol is the major corticoid secreted by the adrenal gland of the guinea-pig. Previous study (1, 2) allowed, by continuous infusion technics, to measure the metabolic clearance rate (MCRF) of cortisol and its production rate (PRF), which represents the secretion rate of the hormone by the adrenal gland (QF) and the peripheral production of cortisol (F) from cortisone (E). In the human
(3), adrenal gland secretes
equal amounts of cortisone and cortisol. In the baboon, all the cortisone production is derived from secreted cortisol (4). Employing a conti14C -cortisol and 3H -cortisone given simultaneously, Cl c1 we studied the interconversion of F and E and the secretion of E by the nuous infusion of
adrenal gland in adult male guinea-pigs.
Vohme
39, Nwnber 1
S
-.rIIROXDrn
January,
1982
S
?B?IIROXDS
MATERIALS AND METHODS Animals The study was carried out using adult male guinea-pigs (DunkinHartley strain) born and bred in the laboratory, Five months after birth young males were placed in individual cages until the experiment at 6 months of age. Four days before administration of labelled hormones, catheters were inserted into the left carotid artery and the right jugular vein under chloral anaesthesia (2%, 2 ml per 100 g body weight). The free ends of catheters were exteriorized at the base of the neck (5). Tracer administration and blood sampling b,2-3H]-cortisone (40-60 Cj/mmol) and [4-14C]-cortisol (50-60 Gil mol) were obtained from New Nuclear Corporation (Dreieich, Germany). Radiochemical purity was established immediatly before use by paper chromatography in the solvent system toluene:methanol:water (2:l:l by vol) (6). Infusion of [l,2-3HJ- cortisone (0.073 t 0.005 uCi/min) and b-14C]cortisol (0.0197 t 0.0007 pCi/min), dissolved in ethanol (50 ~1) and sterile 0.9% NaCl solution (3 ml), was performed simultaneously at a constant rate (1.2 ml/h) in the conscious guinea-pig. After equilibrium was reached at 120 min of infusion (5), the arterial blood (2 ml) was sampled at 130 and 150 min of infusion. Immediatly after sampling, the blood was centrifuged for 10 min at 3,OOOxg and the plasma samples were frozen at -25°C until analysis, which was performed during the month after the ex~riment. Analysis of hormones and calculation of cortisol metabolism The concentrations of radioactive cortisol and cortisone were measured from 0.5 ml of plasma. Endogenous concentrations of cortisol and cortisone were assayed respectively from 100 ~1 and 500 or 1000 ~1 of plasma. Since no tracer could be added to the plasma for the estimation of the manipulative losses, the percentage recovery of the hormones was determined in external standards (with tritiated cortisol and cortisone) which were placed between the plasma samples. Steroids in plasma and external standards were extracted with chloroform and isolated by paper chromatography (toluene:met~anol:water, 2:l:l by vol.). Cortisol and cortisone from the 0.5 ml plasma samples were eluted with methanol into vials, dried, and added with 10 ml of scintillation counting solution. The counting solution was prepared by mixing 5.5 g of Pe~ablend III (Packard) in one liter of toluene. The radioactivity was counted on a Packard Tricarb liquid scintillation spectrometer, with dual isotope settings giving efgiciencies of 30% for 3H and 70% for 14C . There was no overlap of H into the 14C channel and 6% overlap of 14C into 3H channel. Endogenous cortisol and cortisone from 50 ~1 and 500 or 1OOOpl plasma samples were eluted with methanol and distributed into 20-50" 100 ~1 aliquots for cortisol and into 50-100-200-300 ~1 aliquots for cortisone. The endogenous concentrations of steroids were determined
s
TIIEOXDI
83
according to the protein-binding procedure of MURPHY (7) modified in our laboratory (8). abelled F end E added during infusion were negligiP H]-cortisol used for protein binding determinations. - tracer in the aliquot was estimated to less than 0.1 ng/500 ti for cortisone and less than 0.003 ng/lOO ~1 for cortisol. Calculation of the various parameters The MCR and interconversion were determined using the formulae of GURPIDE (9). Parameters of the metabolism of E nd F wer from the specific activities of 3H-F, I4C-F, s H-E and !4;a;cu;;;;;s I and 2 give individual values of different parameters and mean'+ - SM. RESULTS Plasma concentrations and MCR Plasma concentrations of endogenous hormones and MCR were calculated from the mean of the values obtained at 130 and 150 min of infusion. Cortisone plasma level represented about 16% of the F plasma level. MCRE was four times the MCRF (Table 1). Production rates and secretion rates (Table 1 and Table 2) Production rate (PRF) of cortisol which included the secretion rate (QF) and the part of the secretion of E converted into F, did not differ significantly from the secretion rate of cortisol. In contrast, production rate of E (PRE) was much higher (P < 0.001) than its secretion rate (Q,). Little or no E was secreted.
Transfer percentage and interconversion rates (Table 2,) The percentage of E, which was transformed into F (80 t 3) was significantly higher than the percentage of F which was converted into E (59 t 4). The rates of conversion of F into E (rFE) and E into F (rEF) were identical. The part of the secretion of F which was transformed into E ( FE.QF) was equal to the production rate of E.
S
84
‘X’IDROXDb
Kates of irreversible metabolism_(rF and rE) ~--~ At steady state rF = QF + rEF - rFE. The rate of irreversible metabolism results from the rate of cortisol which is secreted by the gland
(C)F), the rate of cortisol which is derived from cortisone (rEF) and the rate of cortisol which is transformed into cortisone (rFE). The rate of irreversible metabolism of F {r-t') was more than three times the rate of irreversible metabolism of E (6).
DISCUSSION Our results for the metabolic clearance rate of E and i are in accordance with those in other species. Indeed, in the human (10) and baboon (4) the MCRE is more than three times the MCRE. In the sheep (11) the MCRE is about twice the MCRE. The difference in the MCR of cortisol and cortisone is probably due in part to the lower binding affinity of corticosteroid-binding-globulin
(CBG) for E, compared with that for F
(7). The affinity constants of guinea-pig complexes were estimated at 2.8 + 0.3 M-I x
10m7 with F and at 0.16 -+ 0.04 11-I x 10-T with E (12)
by equilibrium dialysis. The secretion rate of cortisol (107 pg/h) in our findings was found to be identical tothatobtained
using cannula-
tion of the adrenal vein (119 vg/h) in adu7t male guinea-pig (13) with a cortisol plasma level (about 30 wg/lOO ml) similar to that in our experiment. Our results (Table 2) show that adrenal gland secretes essentially cortisol and that in conscious unstressed guinea-pig the production rate of cortisol is equivalent to its secretion rate. In contrast, the major part of cortisone production is derived from secreted cortisol. Identical results has been obtained in the nonpregnant baboons (4). It has been found (3) an equal secretion rate of cortisol
and cortisone by the adrenal gland of unstressed man. The high speed of interconversion between the two products suggests that liver is probably the main site of these reactions. Moreover, it was demonstrated that a part of the conversion occurs also in viscera and kidney. Indeed, in the 3H -cortisone (i.e. 30% of the sheep (11) a greater concentration of CI [3H]-cortisol concentration) derived from infused [3H]-cortisol occured in the portal venous plasma than in the carotid. The oxidation of F to E was also shown in the human kidney (14). Other extrahepatic tissues such as the heart (15) are able to convert cortisol into cortisone.
In
adult male guinea-pig anaesthetized with nembutal, we have measured the [H3]-E concentration (dpn/ml) derived from infused [H31-cortisol which I_
_.I
represents 36 + 5% of the [~3]-F concentration in the mesenteric vein and 17 + 3% in the renal vein (unpublished data). The greater value of the transfer percentage for the conversion E\F
compared to the reverse reaction F-E
indicates that formation
of cortisol is favored. This findings are compatible with the fact that in guinea-pig cortisol is excreted in the urine principally as 2a- and 6 j9 -hydroxycortisol and
2oa- and 20 p-dihydrocortisol
(16).
It is concluded that in adult male guinea-pig, there is a high rate of interconversion between cortisol and cortisone. The whole pool of cortisone derives from peripheral conversion of cortisol into cortisone and it could be considered that cortisol and cortisone in these conditions form a single pool.
REFERENCES 1. Manin, M. and Delost, P., J. Physiol. (Paris) 74, 687 (1978). 2. Manin, M. and Delost, P., J. Endocrinol. 89, 443 (1980). 3. Bailey, E. and West, H.F., Acta Endocrinologica 62, 339 (1969).
4. Pepe, G.J., Ehrenkranz, R.A. and Towsley, J.D., Endocrinology -' 99 597 (1976). 5. Manin, M. and Delost, P., J. Physiol. (Paris) 73, 47 (1977). Biochemical Journal 50, 370 (1952). 6. Bush, I.E., 7. Murphy, B.E.P., J. Clin. Endocrinol. Metab. 27, 973 (1967). 8. Dalle, M. and Delost, P., J. Endocrinol. 70, 207 (1976). 9. Gurpide, E., Acta Endocrinologica Suppl. 158, 26 (1972). 10. Dazord, A., Saez, J. and Bertrand, J., J. Clin. Endocrinol. Metab. 35, 24 (1972). 11. Paterson, J.Y.F. and Harrison, F.A., J. Endocrinol. 55, 335 (1972). 12. Mickelson, K.E. and Westphal, U., Biochemistryg, 585 (1980). 13. Fajer, A.B. and Vogt, M., J. Physiol. (G.B.) 169, 373 (1963). 14. Hellman, L., Nakada, F., Zumoff, B., Fukushima, D., Bradlow, H.L. and Gallagher, T.F., J. Clin. Endocrinol. Metab. 2, 52 (1971). 15. Kolanowski, J., Corcelle-Cerf, F. and Lammerant, J., J. Steroid Biochem. 14, 773 (1981). 16. Pasqualini, J.R., Costa Novaes, S., Ito, Y. and Nguyen, B.L. J. Steroid Biochem. 1, 341 (1970). 17. The following trivial names are used in this paper : 2a-hydroxycortisol : 2a,11~,17,21-tetrahydroxy-4-pregnene-3,20-dione 6P-hydroxycortisol : 6~,1lp,l7,21-tetrahydroxy-4-pregnene-3,20-dione 20a-dihydrocortisol : 11~,17,20Q,21-tetrahydroxy-4-pregnen-3-one 20P-dihydrocortisol : 11~,17,20f3,21-tetrahydroxy-4-pregnen-3-one
0.10
9.49
3.86
7
8
0.9 + 084
0.16
0.50
5.74
6
7.1 t 0,9
2,64
9.16
5
x + SEM
2.14
2.03
7.70
10.81
4
0
5.02
2
3
0
t
4.72
QF
pmoles/24
1
Animal ND -,-
8.6 -t 0,9
13.34
9.25
7.9
10.7
a.5
6.2
5.1
8.1
rfE
h umoles/24
8 + 1
12.8
8.3
s*4
10.0
7.5
5.8
3.9
7.1
-
rEF h cLmoles/24 h 1 m”-
l--
+
59 4
79.9
51.8
65.1
56.1
46.5
45.7
57.1
68.6
%
PFE
+
80 3
95.3
85.5
73.5
74.5
71.5
69.7
76.1
87.3
Table 2. Secretion rates of cortisol (Q,c)and cortisone (QE), rates of interconversion of cortisol into cortisone (rFE) and of cortisone into cartisol (rEF), rates of irreversible metabolism of cortisol (rF) and cortisone (rE), conversion factors of cortisol into cartisone @FE) and cortisone into cortisol (@IF) in adult canscious male guinea-pigs.
954
i
870
7
8
833 + 20
820
6
x + SEM -
775
824
4
819
3
5
773
2
(9)
827
j-
!
, body weight
I Animal
1
Animal N"
T
665 + - 59
743.0
838.8
682.1
446.9
537.8
446.9
848.5
773.1
Adrenal weight (mg)
0.8 + 0.1 -
0.428
0.993
0.648
0.932
1.287
0.753
0.585
I
I -+ 0.02
0.13
0.069
0.180
0.076
0.192
0.250
0.148
0.065
-~~
0.078
umoles/l
umoles/l 0.469
E
F
9.3
9.9
9.0
11.9
9.50
12.10
8.71
40 +3 -
46.2
30.0
50.3
40.3
28.4
38.2
44.2
42.2
l/24 h
l/24 h ~~_~__ 9.98
MCRF
MCRF
1 , 10.0 ; -+ 0.5
/
I-
I j
I
__-
+1 _
8
3.97
9.92
5.81
11.1
12.20
9.12
5.10
4.68
pmoles/24 h
PRF
4.9 _+ 0.7
3.22
5.41
3.83
7.77
7.07
5.66
2.86
3.27
umoles/24
PRE h
Table 1. Plasma cortisol concentrations (F), plasma cortisone concentrations (E), metabol ic: clearance rates of cortisol (MCRF) and cortisone (MCRE), production rates of cortisol (PRF and cortisone (PRE), in adult conscious male guinea-pigs.
81
MEASUREMENT OF THE RATE OF SECRETION, PERIPHERAL METABOLISM AND INTERCONVERSION OF CORTISOL AND CORTISONE IN AWLT CONSCIOUS MALE GUINEA-PIGS M. Manin, C. Tournaire and P. Delost Laboratoire de Physiologie Animale et ERA CNRS d'Endocrinologie du Developpement Universite de Clermont-Ferrand, Ensemble Scientifique des Cezeaux B.P. 45, 63170 Aubiere, France Received 11-12-81 ABSTRACT Metabolism of the c rtisol (F) and the cortisone (E) was studied by continuous infusion of [P4C]-F and PHI-E in adult conscious male guineapigs. Parameters, calculated from the specific activities of F and E, are expressed in umoles/24 h : production rate of F (PRF) = 8 + 1 and E f;E; ; 44.9 f. 0.7 ; secretion rate of F (QF) = 7.1 t 0.9 aYid E (QE) = ; rate of irreversible metabolism of F (rF) = 6.2 t 0.9 and E (rE)-= i.8 t 0.3 ; percentage of transfer of F into E = 59 t-4% and E into F = 80-t 3%. These results demonstrate that adrenal gland in the adult male giiinea-pig secretes essentially cortisol and little or no cortisone. Practically all the pool of E is derived from transformation of F into E ; the major part of E production is reconverted into F. INTRODUCTION Cortisol is the major corticoid secreted by the adrenal gland of the guinea-pig. Previous study (1, 2) allowed, by continuous infusion technics, to measure the metabolic clearance rate (MCRF) of cortisol and its production rate (PRF), which represents the secretion rate of the hormone by the adrenal gland (QF) and the peripheral production of cortisol (F) from cortisone (E). In the human
(3), adrenal gland secretes
equal amounts of cortisone and cortisol. In the baboon, all the cortisone production is derived from secreted cortisol (4). Employing a conti14C -cortisol and 3H -cortisone given simultaneously, Cl c1 we studied the interconversion of F and E and the secretion of E by the nuous infusion of
adrenal gland in adult male guinea-pigs.
Vohme
39, Nwnber 1
S
-.rIIROXDrn
January,
1982
S
?B?IIROXDS
MATERIALS AND METHODS Animals The study was carried out using adult male guinea-pigs (DunkinHartley strain) born and bred in the laboratory, Five months after birth young males were placed in individual cages until the experiment at 6 months of age. Four days before administration of labelled hormones, catheters were inserted into the left carotid artery and the right jugular vein under chloral anaesthesia (2%, 2 ml per 100 g body weight). The free ends of catheters were exteriorized at the base of the neck (5). Tracer administration and blood sampling b,2-3H]-cortisone (40-60 Cj/mmol) and [4-14C]-cortisol (50-60 Gil mol) were obtained from New Nuclear Corporation (Dreieich, Germany). Radiochemical purity was established immediatly before use by paper chromatography in the solvent system toluene:methanol:water (2:l:l by vol) (6). Infusion of [l,2-3HJ- cortisone (0.073 t 0.005 uCi/min) and b-14C]cortisol (0.0197 t 0.0007 pCi/min), dissolved in ethanol (50 ~1) and sterile 0.9% NaCl solution (3 ml), was performed simultaneously at a constant rate (1.2 ml/h) in the conscious guinea-pig. After equilibrium was reached at 120 min of infusion (5), the arterial blood (2 ml) was sampled at 130 and 150 min of infusion. Immediatly after sampling, the blood was centrifuged for 10 min at 3,OOOxg and the plasma samples were frozen at -25°C until analysis, which was performed during the month after the ex~riment. Analysis of hormones and calculation of cortisol metabolism The concentrations of radioactive cortisol and cortisone were measured from 0.5 ml of plasma. Endogenous concentrations of cortisol and cortisone were assayed respectively from 100 ~1 and 500 or 1000 ~1 of plasma. Since no tracer could be added to the plasma for the estimation of the manipulative losses, the percentage recovery of the hormones was determined in external standards (with tritiated cortisol and cortisone) which were placed between the plasma samples. Steroids in plasma and external standards were extracted with chloroform and isolated by paper chromatography (toluene:met~anol:water, 2:l:l by vol.). Cortisol and cortisone from the 0.5 ml plasma samples were eluted with methanol into vials, dried, and added with 10 ml of scintillation counting solution. The counting solution was prepared by mixing 5.5 g of Pe~ablend III (Packard) in one liter of toluene. The radioactivity was counted on a Packard Tricarb liquid scintillation spectrometer, with dual isotope settings giving efgiciencies of 30% for 3H and 70% for 14C . There was no overlap of H into the 14C channel and 6% overlap of 14C into 3H channel. Endogenous cortisol and cortisone from 50 ~1 and 500 or 1OOOpl plasma samples were eluted with methanol and distributed into 20-50" 100 ~1 aliquots for cortisol and into 50-100-200-300 ~1 aliquots for cortisone. The endogenous concentrations of steroids were determined
s
TIIEOXDI
83
according to the protein-binding procedure of MURPHY (7) modified in our laboratory (8). abelled F end E added during infusion were negligiP H]-cortisol used for protein binding determinations. - tracer in the aliquot was estimated to less than 0.1 ng/500 ti for cortisone and less than 0.003 ng/lOO ~1 for cortisol. Calculation of the various parameters The MCR and interconversion were determined using the formulae of GURPIDE (9). Parameters of the metabolism of E nd F wer from the specific activities of 3H-F, I4C-F, s H-E and !4;a;cu;;;;;s I and 2 give individual values of different parameters and mean'+ - SM. RESULTS Plasma concentrations and MCR Plasma concentrations of endogenous hormones and MCR were calculated from the mean of the values obtained at 130 and 150 min of infusion. Cortisone plasma level represented about 16% of the F plasma level. MCRE was four times the MCRF (Table 1). Production rates and secretion rates (Table 1 and Table 2) Production rate (PRF) of cortisol which included the secretion rate (QF) and the part of the secretion of E converted into F, did not differ significantly from the secretion rate of cortisol. In contrast, production rate of E (PRE) was much higher (P < 0.001) than its secretion rate (Q,). Little or no E was secreted.
Transfer percentage and interconversion rates (Table 2,) The percentage of E, which was transformed into F (80 t 3) was significantly higher than the percentage of F which was converted into E (59 t 4). The rates of conversion of F into E (rFE) and E into F (rEF) were identical. The part of the secretion of F which was transformed into E ( FE.QF) was equal to the production rate of E.
S
84
‘X’IDROXDb
Kates of irreversible metabolism_(rF and rE) ~--~ At steady state rF = QF + rEF - rFE. The rate of irreversible metabolism results from the rate of cortisol which is secreted by the gland
(C)F), the rate of cortisol which is derived from cortisone (rEF) and the rate of cortisol which is transformed into cortisone (rFE). The rate of irreversible metabolism of F {r-t') was more than three times the rate of irreversible metabolism of E (6).
DISCUSSION Our results for the metabolic clearance rate of E and i are in accordance with those in other species. Indeed, in the human (10) and baboon (4) the MCRE is more than three times the MCRE. In the sheep (11) the MCRE is about twice the MCRE. The difference in the MCR of cortisol and cortisone is probably due in part to the lower binding affinity of corticosteroid-binding-globulin
(CBG) for E, compared with that for F
(7). The affinity constants of guinea-pig complexes were estimated at 2.8 + 0.3 M-I x
10m7 with F and at 0.16 -+ 0.04 11-I x 10-T with E (12)
by equilibrium dialysis. The secretion rate of cortisol (107 pg/h) in our findings was found to be identical tothatobtained
using cannula-
tion of the adrenal vein (119 vg/h) in adu7t male guinea-pig (13) with a cortisol plasma level (about 30 wg/lOO ml) similar to that in our experiment. Our results (Table 2) show that adrenal gland secretes essentially cortisol and that in conscious unstressed guinea-pig the production rate of cortisol is equivalent to its secretion rate. In contrast, the major part of cortisone production is derived from secreted cortisol. Identical results has been obtained in the nonpregnant baboons (4). It has been found (3) an equal secretion rate of cortisol
and cortisone by the adrenal gland of unstressed man. The high speed of interconversion between the two products suggests that liver is probably the main site of these reactions. Moreover, it was demonstrated that a part of the conversion occurs also in viscera and kidney. Indeed, in the 3H -cortisone (i.e. 30% of the sheep (11) a greater concentration of CI [3H]-cortisol concentration) derived from infused [3H]-cortisol occured in the portal venous plasma than in the carotid. The oxidation of F to E was also shown in the human kidney (14). Other extrahepatic tissues such as the heart (15) are able to convert cortisol into cortisone.
In
adult male guinea-pig anaesthetized with nembutal, we have measured the [H3]-E concentration (dpn/ml) derived from infused [H31-cortisol which I_
_.I
represents 36 + 5% of the [~3]-F concentration in the mesenteric vein and 17 + 3% in the renal vein (unpublished data). The greater value of the transfer percentage for the conversion E\F
compared to the reverse reaction F-E
indicates that formation
of cortisol is favored. This findings are compatible with the fact that in guinea-pig cortisol is excreted in the urine principally as 2a- and 6 j9 -hydroxycortisol and
2oa- and 20 p-dihydrocortisol
(16).
It is concluded that in adult male guinea-pig, there is a high rate of interconversion between cortisol and cortisone. The whole pool of cortisone derives from peripheral conversion of cortisol into cortisone and it could be considered that cortisol and cortisone in these conditions form a single pool.
REFERENCES 1. Manin, M. and Delost, P., J. Physiol. (Paris) 74, 687 (1978). 2. Manin, M. and Delost, P., J. Endocrinol. 89, 443 (1980). 3. Bailey, E. and West, H.F., Acta Endocrinologica 62, 339 (1969).
4. Pepe, G.J., Ehrenkranz, R.A. and Towsley, J.D., Endocrinology -' 99 597 (1976). 5. Manin, M. and Delost, P., J. Physiol. (Paris) 73, 47 (1977). Biochemical Journal 50, 370 (1952). 6. Bush, I.E., 7. Murphy, B.E.P., J. Clin. Endocrinol. Metab. 27, 973 (1967). 8. Dalle, M. and Delost, P., J. Endocrinol. 70, 207 (1976). 9. Gurpide, E., Acta Endocrinologica Suppl. 158, 26 (1972). 10. Dazord, A., Saez, J. and Bertrand, J., J. Clin. Endocrinol. Metab. 35, 24 (1972). 11. Paterson, J.Y.F. and Harrison, F.A., J. Endocrinol. 55, 335 (1972). 12. Mickelson, K.E. and Westphal, U., Biochemistryg, 585 (1980). 13. Fajer, A.B. and Vogt, M., J. Physiol. (G.B.) 169, 373 (1963). 14. Hellman, L., Nakada, F., Zumoff, B., Fukushima, D., Bradlow, H.L. and Gallagher, T.F., J. Clin. Endocrinol. Metab. 2, 52 (1971). 15. Kolanowski, J., Corcelle-Cerf, F. and Lammerant, J., J. Steroid Biochem. 14, 773 (1981). 16. Pasqualini, J.R., Costa Novaes, S., Ito, Y. and Nguyen, B.L. J. Steroid Biochem. 1, 341 (1970). 17. The following trivial names are used in this paper : 2a-hydroxycortisol : 2a,11~,17,21-tetrahydroxy-4-pregnene-3,20-dione 6P-hydroxycortisol : 6~,1lp,l7,21-tetrahydroxy-4-pregnene-3,20-dione 20a-dihydrocortisol : 11~,17,20Q,21-tetrahydroxy-4-pregnen-3-one 20P-dihydrocortisol : 11~,17,20f3,21-tetrahydroxy-4-pregnen-3-one
0.10
9.49
3.86
7
8
0.9 + 084
0.16
0.50
5.74
6
7.1 t 0,9
2,64
9.16
5
x + SEM
2.14
2.03
7.70
10.81
4
0
5.02
2
3
0
t
4.72
QF
pmoles/24
1
Animal ND -,-
8.6 -t 0,9
13.34
9.25
7.9
10.7
a.5
6.2
5.1
8.1
rfE
h umoles/24
8 + 1
12.8
8.3
s*4
10.0
7.5
5.8
3.9
7.1
-
rEF h cLmoles/24 h 1 m”-
l--
+
59 4
79.9
51.8
65.1
56.1
46.5
45.7
57.1
68.6
%
PFE
+
80 3
95.3
85.5
73.5
74.5
71.5
69.7
76.1
87.3
Table 2. Secretion rates of cortisol (Q,c)and cortisone (QE), rates of interconversion of cortisol into cortisone (rFE) and of cortisone into cartisol (rEF), rates of irreversible metabolism of cortisol (rF) and cortisone (rE), conversion factors of cortisol into cartisone @FE) and cortisone into cortisol (@IF) in adult canscious male guinea-pigs.
954
i
870
7
8
833 + 20
820
6
x + SEM -
775
824
4
819
3
5
773
2
(9)
827
j-
!
, body weight
I Animal
1
Animal N"
T
665 + - 59
743.0
838.8
682.1
446.9
537.8
446.9
848.5
773.1
Adrenal weight (mg)
0.8 + 0.1 -
0.428
0.993
0.648
0.932
1.287
0.753
0.585
I
I -+ 0.02
0.13
0.069
0.180
0.076
0.192
0.250
0.148
0.065
-~~
0.078
umoles/l
umoles/l 0.469
E
F
9.3
9.9
9.0
11.9
9.50
12.10
8.71
40 +3 -
46.2
30.0
50.3
40.3
28.4
38.2
44.2
42.2
l/24 h
l/24 h ~~_~__ 9.98
MCRF
MCRF
1 , 10.0 ; -+ 0.5
/
I-
I j
I
__-
+1 _
8
3.97
9.92
5.81
11.1
12.20
9.12
5.10
4.68
pmoles/24 h
PRF
4.9 _+ 0.7
3.22
5.41
3.83
7.77
7.07
5.66
2.86
3.27
umoles/24
PRE h
Table 1. Plasma cortisol concentrations (F), plasma cortisone concentrations (E), metabol ic: clearance rates of cortisol (MCRF) and cortisone (MCRE), production rates of cortisol (PRF and cortisone (PRE), in adult conscious male guinea-pigs.