228 Horm. Metab. Res. 9 (1977) 228-231
© Georg Thieme Verlag Stuttgart
Dose-Dependent Effect of TRH on Plasma Oleic Acid in Man C. Blum*. R. Huron. J.P. Desager and C. Harvengt Laboratoire de Pathologie Gllnllrale. Facultll de MecJecine, et Laboratoire de Statistique, Universitll Paul-Sabatier. Toulouse. France and Laboratoire de Pharmacothllrapie, Universitll Catholique de Louvain. Belgique
Administered to normal subjects oe either sex, the TRH enhances the plasma oleic acid after 60 minutes without any significantly marked modification in the blood concentration oe total FFA. The oleic acid increase is significantly dependent on the amount oe administered TRH (200 j.lg and .. 400 j.lg). It is accompanied by 1) a more or less pronounced but acute release of TSH, and 2) a rise in circulating T3 but a submaximal value within the time-course of the experiment (1 h). This elevation is presumably due to a preferential liberation of oleic acid by the adipose tissue, through a direct action of TSH and/or under the permissive influence of the thyroid hormone, among other factors that may intervene in the proeess. Key-Words: TRH -Humt1n BloOO - FFA - Oleic Acid TSH - T3
The TRH test was carried out as classically described for clinical investigation (Olmston), over aperiod of one hour and with three measurements (time 0, 20 minutes, 60 minutes). The dose of synthetic TRH (acetic salt: Hoffmann-Laroche Laboratories, Basel, Switzerland) was administered by rapid Lv, injection to each subject, fasting and recumbent during test, after a rest of about 30 minutes. The women were tested immediately after their menstrual period. A third group oe 9 Freneh subjects (6 males, 3 females, ages: 22-32 years, average: 26 years) received an i.v. volume of saline (Nael 0,9%) equivalent to the volume of TRH injected. This control group included 7 subjects (from the second group) who were used as controls for themselves. The venous blood sampIes were withdrawn in triplicate during the experimental time-course. The TSH level was determined by radioimmunoassay with double antibody technique (Odell er al., Beckers er al.), the cireulating T 3 by radioimmunoassay (Dutau er al.,) only in the group given ;;. 400 j.lg of TRH.
The FF A concentrations were measured in heparinized plasma after immediate centrifugation and storage at _20 0 , In spite of the hormonal effects of the TRH (thyro- according to the gas-chromatographic method described by tropinreleasing hormone) on the pituitary - thyroid Hagenteid and modified as folIows: methylation by diazomethane, PYE 104 analyser equipped with flame ionizasystem in man under normal conditions, many aution detector and with auto solid injector, using C 21 fatty thors have pointed out that glucose, insulin and free acid as internal standard (heneicosanoic acid), 5 ft column fatty acid (FFA) concentrations in the plasma are packed with 18% Hiett - I BP on gas chrom P 100-200 mesh. The amounts of FF A were expressed in j.lEq/l, the unaffected. levels of the successive individual fractions in % j.lEq/l of The present study was undertaken to examine wheth- the total FFA values.
Introduction
er or not the response to TRH, administered in in· creasing doses, modifies the concentration in blood ReSldts of total FFA and the one of their individual fractions. The responses are summanze . d'In T ableIßlVI 1 (' d"d uaI Materials and Methods variations) and in Table 2 (absolute mean values). Due to the extreme variability of the initial values The subjects, selected among the students and the hospital at time 0 in the tested subjects, the statistical study staff, all welHnformed and volunteer for the experiment, has been based on the variations in percentage and were healthy and euthyroid. on the comparison of the means of each group in a One first group of 10 Belgian subjects (7 males, 3 females, variance analysis. ages: 20-45 years, average: 28 years) were tested by ade ministration of 200 j.lg of TRH. A second group of 9 French subjects (6 males, 3 females, aaes: 22-28 years, average: 25 years) were given doses of TRH superior to 200 j.lg: 4 subjects received 400 j.lg, 2 subjects 600 j.lg, 3 subjects 800 j.lg.
The calculation indicates that the 9 subjects who received increasing quantities of TRH, all of them superior to 200 Ilg (400, 600 or 800 Ilg) did not show a significantly different response according to the doses and might be pooled in an homogeneous group tested with ;;, 400 pg.
*Institut National de la Sant~ et de la Recherche Medicale (Inserm, Paris, France)
The following facts were observed (Table 2 and Fig. 1):
Received: 29 Dec. 1975 Accepted: 25 Oet. 1976
- in the subjects given 200 Ilg of TRH (n = 10), the TSH trebled at the 20th minute and was still double
Revised: 29 June 1976
Downloaded by: NYU. Copyrighted material.
Summary
Effect of TRH on Plasma Oleic Acid
229
TRH
FFA jlEq/1 0
20 min
60 min
Oleic acid % jlEq/1 0 20 min
60 min
664 854 368 1022 932 649 681 995 944 485
661 742 615 1039 856 703 605 1020 1130 451
615 744 595 1332 851 1005 712 742 1113 454
33 26 24 34 32 25 32 34 31 22
33 27 26 36 34 27 32 36 32 24
34 29 27 38 36 32 33 37 34 25
400 jlB (n =4)
308 300 374 247
440 300 431 263
419 316 415 419
26 27 30 25
28 30 37 27
30 31 34 32
600 jlB (n = 2)
407 438
357 399
567 349
31 32
33 34
37 36
800 jlg (n = 3)
394 214 411
378 247 452
399 304 489
26 20 31
27 21 34
32 27 38
200 jlg (n = 10)
Table 2 Variations of circulating TSH, T3, total FFA and oleic acid after TRH administration in increasing doses (mean ± SEM). Subjects treated with 200 jlB TRH: n = 10 (Belgian subjects). SUbjects treated with .. 400 jlg TRH: n = 9
© Georg Thieme Verlag Stuttgart
Dose-Dependent Effect of TRH on Plasma Oleic Acid in Man C. Blum*. R. Huron. J.P. Desager and C. Harvengt Laboratoire de Pathologie Gllnllrale. Facultll de MecJecine, et Laboratoire de Statistique, Universitll Paul-Sabatier. Toulouse. France and Laboratoire de Pharmacothllrapie, Universitll Catholique de Louvain. Belgique
Administered to normal subjects oe either sex, the TRH enhances the plasma oleic acid after 60 minutes without any significantly marked modification in the blood concentration oe total FFA. The oleic acid increase is significantly dependent on the amount oe administered TRH (200 j.lg and .. 400 j.lg). It is accompanied by 1) a more or less pronounced but acute release of TSH, and 2) a rise in circulating T3 but a submaximal value within the time-course of the experiment (1 h). This elevation is presumably due to a preferential liberation of oleic acid by the adipose tissue, through a direct action of TSH and/or under the permissive influence of the thyroid hormone, among other factors that may intervene in the proeess. Key-Words: TRH -Humt1n BloOO - FFA - Oleic Acid TSH - T3
The TRH test was carried out as classically described for clinical investigation (Olmston), over aperiod of one hour and with three measurements (time 0, 20 minutes, 60 minutes). The dose of synthetic TRH (acetic salt: Hoffmann-Laroche Laboratories, Basel, Switzerland) was administered by rapid Lv, injection to each subject, fasting and recumbent during test, after a rest of about 30 minutes. The women were tested immediately after their menstrual period. A third group oe 9 Freneh subjects (6 males, 3 females, ages: 22-32 years, average: 26 years) received an i.v. volume of saline (Nael 0,9%) equivalent to the volume of TRH injected. This control group included 7 subjects (from the second group) who were used as controls for themselves. The venous blood sampIes were withdrawn in triplicate during the experimental time-course. The TSH level was determined by radioimmunoassay with double antibody technique (Odell er al., Beckers er al.), the cireulating T 3 by radioimmunoassay (Dutau er al.,) only in the group given ;;. 400 j.lg of TRH.
The FF A concentrations were measured in heparinized plasma after immediate centrifugation and storage at _20 0 , In spite of the hormonal effects of the TRH (thyro- according to the gas-chromatographic method described by tropinreleasing hormone) on the pituitary - thyroid Hagenteid and modified as folIows: methylation by diazomethane, PYE 104 analyser equipped with flame ionizasystem in man under normal conditions, many aution detector and with auto solid injector, using C 21 fatty thors have pointed out that glucose, insulin and free acid as internal standard (heneicosanoic acid), 5 ft column fatty acid (FFA) concentrations in the plasma are packed with 18% Hiett - I BP on gas chrom P 100-200 mesh. The amounts of FF A were expressed in j.lEq/l, the unaffected. levels of the successive individual fractions in % j.lEq/l of The present study was undertaken to examine wheth- the total FFA values.
Introduction
er or not the response to TRH, administered in in· creasing doses, modifies the concentration in blood ReSldts of total FFA and the one of their individual fractions. The responses are summanze . d'In T ableIßlVI 1 (' d"d uaI Materials and Methods variations) and in Table 2 (absolute mean values). Due to the extreme variability of the initial values The subjects, selected among the students and the hospital at time 0 in the tested subjects, the statistical study staff, all welHnformed and volunteer for the experiment, has been based on the variations in percentage and were healthy and euthyroid. on the comparison of the means of each group in a One first group of 10 Belgian subjects (7 males, 3 females, variance analysis. ages: 20-45 years, average: 28 years) were tested by ade ministration of 200 j.lg of TRH. A second group of 9 French subjects (6 males, 3 females, aaes: 22-28 years, average: 25 years) were given doses of TRH superior to 200 j.lg: 4 subjects received 400 j.lg, 2 subjects 600 j.lg, 3 subjects 800 j.lg.
The calculation indicates that the 9 subjects who received increasing quantities of TRH, all of them superior to 200 Ilg (400, 600 or 800 Ilg) did not show a significantly different response according to the doses and might be pooled in an homogeneous group tested with ;;, 400 pg.
*Institut National de la Sant~ et de la Recherche Medicale (Inserm, Paris, France)
The following facts were observed (Table 2 and Fig. 1):
Received: 29 Dec. 1975 Accepted: 25 Oet. 1976
- in the subjects given 200 Ilg of TRH (n = 10), the TSH trebled at the 20th minute and was still double
Revised: 29 June 1976
Downloaded by: NYU. Copyrighted material.
Summary
Effect of TRH on Plasma Oleic Acid
229
TRH
FFA jlEq/1 0
20 min
60 min
Oleic acid % jlEq/1 0 20 min
60 min
664 854 368 1022 932 649 681 995 944 485
661 742 615 1039 856 703 605 1020 1130 451
615 744 595 1332 851 1005 712 742 1113 454
33 26 24 34 32 25 32 34 31 22
33 27 26 36 34 27 32 36 32 24
34 29 27 38 36 32 33 37 34 25
400 jlB (n =4)
308 300 374 247
440 300 431 263
419 316 415 419
26 27 30 25
28 30 37 27
30 31 34 32
600 jlB (n = 2)
407 438
357 399
567 349
31 32
33 34
37 36
800 jlg (n = 3)
394 214 411
378 247 452
399 304 489
26 20 31
27 21 34
32 27 38
200 jlg (n = 10)
Table 2 Variations of circulating TSH, T3, total FFA and oleic acid after TRH administration in increasing doses (mean ± SEM). Subjects treated with 200 jlB TRH: n = 10 (Belgian subjects). SUbjects treated with .. 400 jlg TRH: n = 9
