0021 -972X/78/4703-0647$02.00/0 •Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society
Vol. 47, No. 3 Printed in U.S.A.
Carbidopa Inhibits the Growth Hormone- and ProlactinSuppressive Effect of L-Dopa in Acromegalic Patients F. CAMANNI, G. B. PICOTTI, F. MASSARA, G. M. MOLINATTI, P. MANTEGAZZA, AND E. E. MULLER Chair of Endocrinology, University of Turin, the Department of Pharmacology (First Chair) University of Milan (G.B.P., P.M.), and the Institute of Pharmacology and Pharmacognosy (E.E.M.), University ofCagliari, 09100 Cagliari, Italy ABSTRACT. The plasma GH, PRL, TSH, and dopamine (DA) responses to an infusion of L-dopa were examined in six acromegalic patients before and after pretreatment with carbidopa, a drug which inhibits the peripheral conversion of L-dopa to DA. Carbidopa neither modified baseline DA nor induced changes in baseline GH, PRL, or TSH levels. The drug instead markedly reduced the L-dopa-induced DA rise, an effect which was concomitant to a striking reduction of the suppressive effect of L-dopa on plasma GH and a partial
I
T IS now well established that several dopaminergic compounds, such as L-dopa, apomorphine, 2-Br-a-ergocryptine, and piribedil, induce in many acromegalic subjects a suppressive effect on GH secretion (1-4). This effect is qualitatively abnormal, as normal subjects exhibit augmented GH secretion after the same dopaminergic compounds (3, 5-7). The mechanism (s) whereby the activation of dopamine (DA) receptor sites induces in acromegalics a decrease of GH secretion has yet to be completely clarified. The evidence so far available suggests that these compounds exert their stimulatory action at a central nervous system (CNS) site of action in normal subjects, whereas in acromegaly their inhibitory action is mainly directed to pituitary somatotrophs (8-10). With the aim of investigating the mechanism underlying the GH-suppressive effect of L-dopa in acromegaly (1, 4, 8), we studied in acromegalics the effects of a pretreatment with carbidopa, an inhibitor of the peripheral conversion of L-dopa to DA (11), on the Received November 29,1977. Address requests for reprints to: Dr. E. E. Miiller, c/o Department of Pharmacology, University of Milan, Via Vanvitelli, 32, 20129 Milano, Italy.
inhibition of the suppressive effect of L-dopa on plasma PRL. TSH levels did not change either after L-dopa alone or L-dopa plus carbidopa. These data demonstrate that in "responder" acromegalics, L-dopa inhibits GH secretion through its peripheral conversion to DA and not via activation of central DA neurotransmission. For the effect of L-dopa on PRL secretion, in addition to a peripheral dopaminergic component, a central component cannot be disregarded. (J Clin Endocrinol Metab 47: 647, 1978)
plasma titers of DA and GH after L-dopa administration. In addition, the plasma levels of PRL and TSH, which are under dopaminergic control (12, 13), were concomitantly evaluated. Materials and Methods Five female and three male subjects with clinically active acromegaly, ranging in age from 29-66 yr, were studied. In previous L-dopa tests (500 mg orally), they had suppressed their baseline GH levels from 29-87%. All patients presented varying degrees of sella turcica enlargement. Two patients (nos. 5 and 6) had previously received an intrasellar radioisotope implantation without any significant improvement. All patients gave informed consent to the investigation. All experiments were performed on the morning after an overnight fast. Six subjects (nos. 1-6) underwent an acute test with L-dopa (pretreatment test), after which they received for 3 days 100 mg oral carbidopa (L-hydrazino-a-methyldopa) three times daily at 0700, 1500, and 2300 h. At the completion of carbidopa treatment, i.e. 2 h after the preceding dose, the acute dopa testing was repeated in exactly the same manner as the pretreatment test (posttreatment test). Serial blood specimens were collected through an indwelling polyethylene cannula placed in the antecubital vein and kept open by the slow infusion
647
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JCK & M • 1978 VoU7 • No 3
CAMANNI ET AL.
648
of 0.9% saline. Acute L-dopa testing consisted of the iv infusion, by means of a constant rate pump, for 30 min of 1.25 mg/kg BW of L-dopa (Larodopa, Roche). Blood sampling was carried out at —30, 0, and +30, +45, +60, +75, +90, +120, and +150 min from the starting of the infusion. In two subjects (nos. 7 and 8), only baseline plasma samples were obtained, immediately before and at the end of carbidopa treatment. Plasma GH, PRL, and TSH were assayed by double antibody RIAs, using the CEA-IRE-SORIN kits (Saluggia, Italy). The anti-GH antiserum was highly specific and there was no more than a negligible cross-reaction with PRL (0.2%, where B/B o = 50%). The sensitivity of the assays was 0.2 and 0.3 ng/ml for GH and PRL, respectively, and 0.2 juU/ml for TSH. Plasma DA, norepinephrine (NE), and epinephrine (E) levels were assayed simultaneously in 50 \i\ plasma by a sensitive (~1 pg for NE and E, ~4 pg for DA) radioenzymatic method (14) based on the conversion of the three catecholamines into their respective [3H]O-methylated derivatives by the enzyme COMT1 in the presence of [3H]SAM. In the enzyme preparation used (15), presence of a contaminating L-dopa decarboxylase which may produce false elevations in DA due to in vitro decarboxylation of the precursor (16) was investigated and was found to be negligible. Determinations of plasma catecholamines (CA) during pretreatment and posttreatment L-dopa tests were performed only in four of six subjects (nos. 1-4). Due to the wide range of baseline plasma GH and PRL levels in acromegalic subjects (see Table 1), data were expressed as the percentage of inhibition of baseline levels. CA concentrations in plasma were expressed as absolute values. Statistical analyses were carried out using paired or unpaired t tests.
Results In the eight acromegalic patients of this study, mean basal DA, NE, and E levels were 82 ± 12, 174 ± 14, and 44 ± 9 pg/ml, respectively; these values were not significantly different from those detected in normal subjects (17). Treatment with carbidopa neither significantly modified baseline DA levels (95 ± 21 vs. 88 ± 24 pg/ml; four subjects) nor induced 1 The following abbreviations are used: COMT, catechol-O-methyltransferase; SAM, S-adenosylmethionine.
significant changes in baseline GH, PRL, and TSH titers. In only one case (no. 2) after carbidopa was there a clear-cut rise in PRL r levels (from 34 to 185 ng/ml; Table 1). Infusion with L-dopa (pretreatment test) induced a striking rise in plasma DA levels, . which was maximum at 30 min (P < 0.001 vs. baseline; Fig. 1); this was paralleled by a clearcut but short-lived reduction of GH levels ^ (Fig. 2, upper part). After L-dopa, there was also a marked and long-lasting suppression of plasma PRL (Fig. 2, lower part). A different * pattern was present when the test with L-dopa was repeated after carbidopa administration (posttreatment test). In this instance, the rise in plasma DA levels induced by the CA precursor was strikingly reduced (88 ± 1% inhibition of peak levels at 30 min; Fig. 1) and ^ there was no significant decrease of GH and PRL wth respect to baseline levels (Fig. 2). It * must be noticed, however, that the inhibitory . effect of carbidopa on L-dopa-induced suppression of hormone levels was more pronounced for GH (pretreatment vs. posttreat- ment test, P < 0.01 at 30 min) than for PRL (pretreatment vs. posttreatment test, NS at all time intervals). Plasma TSH levels were neither changed after L-dopa nor after L-dopa plus carbidopa administration (data not presented). Discussion
*
In this series of eight acromegalic patients selected on the basis of their responsiveness . to the GH-suppressive effect of L-dopa, the plasma DA concentrations were within normal range. Also, plasma NE and E concentra- ¥ tions did not differ in acromegalic subjects from those detected in normal subjects, a finding previously reported by Cryer (18). ^ Administration of carbidopa at the dose and during the time lapse used was unable to modify baseline DA, GH, PRL, and TSH lev- , els. The inability of carbidopa to affect baseline DA. concentrations at doses which inhibit peripheral (.rcarboxylase has been noticed also in normal subjects (M. Da Prada, personal communication). Only in one subject was there a clear-cut rise in plasma PRL levels
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CARBIDOPA, GH, AND PRL IN ACROMEGALY
649
TABLE 1. Basal plasma levels of DA, GH, PRL, and TSH in eight acromegalic subjects before and after administration of carbidopa Subject
DA (pg/ml) Age (yr)
Sex
43 32 48 59 29 26 40 37
M F M F F F F
1 2 3 4 5 6 7 8
M
Mean ± SEM
Before
After
125 140 63 53 62 92 45 75
104 149 48 50
GH (ng/ml)
PRL (ng/ml)
TSH OiU/ml)
Before 51.0 25.5 52.5 35.5 22.7 13.0 13.2 13.5
After 49.5 32.0 45.0 39.0 55.0 21.5 17.0 10.7
Before
After
3.7
4.0
34.0 27.0 96.0 25.5
185.0 26.0 91.0 21.7
6.5 6.7
4.5 9.5
12.0
13.0
8.5 8.0 2.5 5.0 4.0
28.4 ±5.8
33.7 ±5.7
26.4 ±10.7
44.3 ±22.4
5.2
5.7
±0.9
±1.2
82 ±12
Before 6.0 2.5
After 3.2 2.5 3.2 9.2
10.5 3.5 9.0 4.7
Each value is the mean of two determinations on samples obtained at 30-min intervals. 700(5
6000
5000
I
of
carbidopa
4000
with carbidopa
lasma
Q 3000
Q_
2OOO
1000
i-30
30
60
90
120
time(min) FIG. 1. Plasma DA concentrations (mean ± SEM) after iv infusion of L-dopa in four acromegalic subjects before and after treatment with carbidopa. Pretreatment test values are significantly different from posttreatment test values at 30 (P < 0.001), 45 (P < 0.05), and 60 min (P < 0.05). For other details see text.
after carbidopa. Recently, an increase in plasma PRL but not GH levels after carbidopa has been reported by Brown et al. (19); it must be noticed, however, that these findings were obtained in normal subjects after a long-last-
ing (7 days) drug treatment. The most striking finding in our study was that concomitant to an almost complete suppression by carbidopa of the L-dopa-induced rise in plasma DA, there was a marked dimi-
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 19:34 For personal use only. No other uses without permission. . All rights reserved.
JCE&M • 1978 Vol47 • No 3
CAMANNI ET AL.
650 20 10
15
s
A ««O
-20 _ _ _ _ _ without carbidopa
"30
—
„ _ . . w i t h carbidopa
-40 -50
• • ^ CO 13
L-DOPA
*10
•
s
"o #
A
J
-10
a. CO
: \i
S -30
-50
;
-
>
A
/
>
a.
-40
•
if
I
0-
>
f
r—
000
'
L
000 j
0
30
60
SO
120
15
The authors thank Dr. Piero Angeletti and Merck, Sharp, and Dohme (Italia) for the gift of carbidopa and Dr. Paolo Priore and Hoffmann La Roche (Italia) for the generous supply of Larodopa. Thanks are given to Miss Rosaria Scirea for secretarial help.
PICOTTI, Plasma adrenaline, noradrenaline and dopamine in man and different animal species, JPhysiol (Land) 276: 311, 1978. 18. CRYER, P. E., Plasma norepinephrine and epinephrine in acromegaly, J Clin Endocrinol Metab 41: 542, 1975. 19. BROWN, G. M., P. E. GARFINKEL, J. J. WARSH, AND H. C.
STANCER, Effect of carbidopa on prolactin, growth hormone and cortisol secretion in man, J Clin Endocrinol Metab 43: 236, 1976. 20. HOKFELT, T., K. FUXE, AND M. GOLDSTEIN, Immunohisto-
References 1. CHIODINI, P. G., A. LIUZZI, L. BOTALLA, G. CREMASCOLI, AND
F. SILVESTRINI, Inhibitory effect of dopaminergic stimulation on growth hormone release in acromegaly, J Clin Endocrinol Metab 38: 200, 1974. 2. LIUZZI, A., P. G. CHIODINI, L. BOTALLA, G. CREMASCOLI, E.
r
E. MiiLLER, AND F. SILVESTRINI, Decreased plasma growth hormone (GH) levels in acromegalics following CB 154 (2-Bra-ergocryptine) administration, J Clin Endocrinol Metab 38: 910, 1974. 3. CAMANNI, F., F. MASSARA, L. BELFORTE, AND G. M. MOLI-
chemical localization of aromatic L-amino acid decarboxylase (dopa decarboxylase) in central dopamine and 5-hydroxytryptamine nerve cell bodies in the rat, Brain Res 53: 175, 1973. 21. LOTTI, V. J., AND C. C. PORTER, Potentiation and inhibition of some central actions of L-dopa by decarboxylase inhibitors, J Pharmacol Exp Ther 172: 406, 1970. 22. PtJHRINGER, W., A. WIRZ-JUSTICE, AND I. LANCRANJAN, Mood elevation and pituitary stimulation after iv 1-5-HTP in normal subjects: evidence for a common serotoninergic mechanism, Neurosci Lett 2: 349, 1976. 23. BROADWELL, R. D., AND M. W. BRIGHTMAN, Entry of peroxidase in neurons of the central and peripheral nervous system
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 19:34 For personal use only. No other uses without permission. . All rights reserved.
652
CAMANNI ET AL.
JCE&M . 1978 Vol47 • No 3 W
from extracerebral and cerebral blood, J Comp Neurol 166: 257, 1976. 24. BARTHOLINI, G., AND A. PLETSCHER, Cerebral accumulation and metabolism of C14-dopa after selective inhibition of peripheral decarboxylase, J Pharmacol Exp Ther 161: 14,1968.
27. CRYER, P. E., AND W. H. DAUGHADAY, Adrenergic modulation of growth hormone secretion in acromegaly: alpha- and betaadrenergic blockade produce qualitative normal responses but no effect on L-dopa suppression, J Clin Endocrinol Metab 44: 977, 1977.
25. MASHITER, K., E. ADAMS, M. BEARD, AND A. HOLLEY, Brom-
28. SZABO, M.,
ocryptine inhibits prolactin and growth hormone release by human pituitary tumors in culture, Lancet 2: 197,1977. 26. MULLER, E. E., G. NISTICO, AND U. SCAPAGNINI, Neurotransmitters and Anterior Pituitary Function, New York, Academic Press, 1977.
C. NAKAWATASE, N. KOVATHANA, AND L.
A.
FROHMAN, Effect of the DOPA decarboxylase inhibitor MK486 on L - D O P A induced inhibition of prolactin secretion. Evidence of CNS participation in the L-DOPA effects, Neu' loendocrinology 24: 24, 1977.
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Vol. 47, No. 3 Printed in U.S.A.
Carbidopa Inhibits the Growth Hormone- and ProlactinSuppressive Effect of L-Dopa in Acromegalic Patients F. CAMANNI, G. B. PICOTTI, F. MASSARA, G. M. MOLINATTI, P. MANTEGAZZA, AND E. E. MULLER Chair of Endocrinology, University of Turin, the Department of Pharmacology (First Chair) University of Milan (G.B.P., P.M.), and the Institute of Pharmacology and Pharmacognosy (E.E.M.), University ofCagliari, 09100 Cagliari, Italy ABSTRACT. The plasma GH, PRL, TSH, and dopamine (DA) responses to an infusion of L-dopa were examined in six acromegalic patients before and after pretreatment with carbidopa, a drug which inhibits the peripheral conversion of L-dopa to DA. Carbidopa neither modified baseline DA nor induced changes in baseline GH, PRL, or TSH levels. The drug instead markedly reduced the L-dopa-induced DA rise, an effect which was concomitant to a striking reduction of the suppressive effect of L-dopa on plasma GH and a partial
I
T IS now well established that several dopaminergic compounds, such as L-dopa, apomorphine, 2-Br-a-ergocryptine, and piribedil, induce in many acromegalic subjects a suppressive effect on GH secretion (1-4). This effect is qualitatively abnormal, as normal subjects exhibit augmented GH secretion after the same dopaminergic compounds (3, 5-7). The mechanism (s) whereby the activation of dopamine (DA) receptor sites induces in acromegalics a decrease of GH secretion has yet to be completely clarified. The evidence so far available suggests that these compounds exert their stimulatory action at a central nervous system (CNS) site of action in normal subjects, whereas in acromegaly their inhibitory action is mainly directed to pituitary somatotrophs (8-10). With the aim of investigating the mechanism underlying the GH-suppressive effect of L-dopa in acromegaly (1, 4, 8), we studied in acromegalics the effects of a pretreatment with carbidopa, an inhibitor of the peripheral conversion of L-dopa to DA (11), on the Received November 29,1977. Address requests for reprints to: Dr. E. E. Miiller, c/o Department of Pharmacology, University of Milan, Via Vanvitelli, 32, 20129 Milano, Italy.
inhibition of the suppressive effect of L-dopa on plasma PRL. TSH levels did not change either after L-dopa alone or L-dopa plus carbidopa. These data demonstrate that in "responder" acromegalics, L-dopa inhibits GH secretion through its peripheral conversion to DA and not via activation of central DA neurotransmission. For the effect of L-dopa on PRL secretion, in addition to a peripheral dopaminergic component, a central component cannot be disregarded. (J Clin Endocrinol Metab 47: 647, 1978)
plasma titers of DA and GH after L-dopa administration. In addition, the plasma levels of PRL and TSH, which are under dopaminergic control (12, 13), were concomitantly evaluated. Materials and Methods Five female and three male subjects with clinically active acromegaly, ranging in age from 29-66 yr, were studied. In previous L-dopa tests (500 mg orally), they had suppressed their baseline GH levels from 29-87%. All patients presented varying degrees of sella turcica enlargement. Two patients (nos. 5 and 6) had previously received an intrasellar radioisotope implantation without any significant improvement. All patients gave informed consent to the investigation. All experiments were performed on the morning after an overnight fast. Six subjects (nos. 1-6) underwent an acute test with L-dopa (pretreatment test), after which they received for 3 days 100 mg oral carbidopa (L-hydrazino-a-methyldopa) three times daily at 0700, 1500, and 2300 h. At the completion of carbidopa treatment, i.e. 2 h after the preceding dose, the acute dopa testing was repeated in exactly the same manner as the pretreatment test (posttreatment test). Serial blood specimens were collected through an indwelling polyethylene cannula placed in the antecubital vein and kept open by the slow infusion
647
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JCK & M • 1978 VoU7 • No 3
CAMANNI ET AL.
648
of 0.9% saline. Acute L-dopa testing consisted of the iv infusion, by means of a constant rate pump, for 30 min of 1.25 mg/kg BW of L-dopa (Larodopa, Roche). Blood sampling was carried out at —30, 0, and +30, +45, +60, +75, +90, +120, and +150 min from the starting of the infusion. In two subjects (nos. 7 and 8), only baseline plasma samples were obtained, immediately before and at the end of carbidopa treatment. Plasma GH, PRL, and TSH were assayed by double antibody RIAs, using the CEA-IRE-SORIN kits (Saluggia, Italy). The anti-GH antiserum was highly specific and there was no more than a negligible cross-reaction with PRL (0.2%, where B/B o = 50%). The sensitivity of the assays was 0.2 and 0.3 ng/ml for GH and PRL, respectively, and 0.2 juU/ml for TSH. Plasma DA, norepinephrine (NE), and epinephrine (E) levels were assayed simultaneously in 50 \i\ plasma by a sensitive (~1 pg for NE and E, ~4 pg for DA) radioenzymatic method (14) based on the conversion of the three catecholamines into their respective [3H]O-methylated derivatives by the enzyme COMT1 in the presence of [3H]SAM. In the enzyme preparation used (15), presence of a contaminating L-dopa decarboxylase which may produce false elevations in DA due to in vitro decarboxylation of the precursor (16) was investigated and was found to be negligible. Determinations of plasma catecholamines (CA) during pretreatment and posttreatment L-dopa tests were performed only in four of six subjects (nos. 1-4). Due to the wide range of baseline plasma GH and PRL levels in acromegalic subjects (see Table 1), data were expressed as the percentage of inhibition of baseline levels. CA concentrations in plasma were expressed as absolute values. Statistical analyses were carried out using paired or unpaired t tests.
Results In the eight acromegalic patients of this study, mean basal DA, NE, and E levels were 82 ± 12, 174 ± 14, and 44 ± 9 pg/ml, respectively; these values were not significantly different from those detected in normal subjects (17). Treatment with carbidopa neither significantly modified baseline DA levels (95 ± 21 vs. 88 ± 24 pg/ml; four subjects) nor induced 1 The following abbreviations are used: COMT, catechol-O-methyltransferase; SAM, S-adenosylmethionine.
significant changes in baseline GH, PRL, and TSH titers. In only one case (no. 2) after carbidopa was there a clear-cut rise in PRL r levels (from 34 to 185 ng/ml; Table 1). Infusion with L-dopa (pretreatment test) induced a striking rise in plasma DA levels, . which was maximum at 30 min (P < 0.001 vs. baseline; Fig. 1); this was paralleled by a clearcut but short-lived reduction of GH levels ^ (Fig. 2, upper part). After L-dopa, there was also a marked and long-lasting suppression of plasma PRL (Fig. 2, lower part). A different * pattern was present when the test with L-dopa was repeated after carbidopa administration (posttreatment test). In this instance, the rise in plasma DA levels induced by the CA precursor was strikingly reduced (88 ± 1% inhibition of peak levels at 30 min; Fig. 1) and ^ there was no significant decrease of GH and PRL wth respect to baseline levels (Fig. 2). It * must be noticed, however, that the inhibitory . effect of carbidopa on L-dopa-induced suppression of hormone levels was more pronounced for GH (pretreatment vs. posttreat- ment test, P < 0.01 at 30 min) than for PRL (pretreatment vs. posttreatment test, NS at all time intervals). Plasma TSH levels were neither changed after L-dopa nor after L-dopa plus carbidopa administration (data not presented). Discussion
*
In this series of eight acromegalic patients selected on the basis of their responsiveness . to the GH-suppressive effect of L-dopa, the plasma DA concentrations were within normal range. Also, plasma NE and E concentra- ¥ tions did not differ in acromegalic subjects from those detected in normal subjects, a finding previously reported by Cryer (18). ^ Administration of carbidopa at the dose and during the time lapse used was unable to modify baseline DA, GH, PRL, and TSH lev- , els. The inability of carbidopa to affect baseline DA. concentrations at doses which inhibit peripheral (.rcarboxylase has been noticed also in normal subjects (M. Da Prada, personal communication). Only in one subject was there a clear-cut rise in plasma PRL levels
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 19:34 For personal use only. No other uses without permission. . All rights reserved.
CARBIDOPA, GH, AND PRL IN ACROMEGALY
649
TABLE 1. Basal plasma levels of DA, GH, PRL, and TSH in eight acromegalic subjects before and after administration of carbidopa Subject
DA (pg/ml) Age (yr)
Sex
43 32 48 59 29 26 40 37
M F M F F F F
1 2 3 4 5 6 7 8
M
Mean ± SEM
Before
After
125 140 63 53 62 92 45 75
104 149 48 50
GH (ng/ml)
PRL (ng/ml)
TSH OiU/ml)
Before 51.0 25.5 52.5 35.5 22.7 13.0 13.2 13.5
After 49.5 32.0 45.0 39.0 55.0 21.5 17.0 10.7
Before
After
3.7
4.0
34.0 27.0 96.0 25.5
185.0 26.0 91.0 21.7
6.5 6.7
4.5 9.5
12.0
13.0
8.5 8.0 2.5 5.0 4.0
28.4 ±5.8
33.7 ±5.7
26.4 ±10.7
44.3 ±22.4
5.2
5.7
±0.9
±1.2
82 ±12
Before 6.0 2.5
After 3.2 2.5 3.2 9.2
10.5 3.5 9.0 4.7
Each value is the mean of two determinations on samples obtained at 30-min intervals. 700(5
6000
5000
I
of
carbidopa
4000
with carbidopa
lasma
Q 3000
Q_
2OOO
1000
i-30
30
60
90
120
time(min) FIG. 1. Plasma DA concentrations (mean ± SEM) after iv infusion of L-dopa in four acromegalic subjects before and after treatment with carbidopa. Pretreatment test values are significantly different from posttreatment test values at 30 (P < 0.001), 45 (P < 0.05), and 60 min (P < 0.05). For other details see text.
after carbidopa. Recently, an increase in plasma PRL but not GH levels after carbidopa has been reported by Brown et al. (19); it must be noticed, however, that these findings were obtained in normal subjects after a long-last-
ing (7 days) drug treatment. The most striking finding in our study was that concomitant to an almost complete suppression by carbidopa of the L-dopa-induced rise in plasma DA, there was a marked dimi-
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 19:34 For personal use only. No other uses without permission. . All rights reserved.
JCE&M • 1978 Vol47 • No 3
CAMANNI ET AL.
650 20 10
15
s
A ««O
-20 _ _ _ _ _ without carbidopa
"30
—
„ _ . . w i t h carbidopa
-40 -50
• • ^ CO 13
L-DOPA
*10
•
s
"o #
A
J
-10
a. CO
: \i
S -30
-50
;
-
>
A
/
>
a.
-40
•
if
I
0-
>
f
r—
000
'
L
000 j
0
30
60
SO
120
15
The authors thank Dr. Piero Angeletti and Merck, Sharp, and Dohme (Italia) for the gift of carbidopa and Dr. Paolo Priore and Hoffmann La Roche (Italia) for the generous supply of Larodopa. Thanks are given to Miss Rosaria Scirea for secretarial help.
PICOTTI, Plasma adrenaline, noradrenaline and dopamine in man and different animal species, JPhysiol (Land) 276: 311, 1978. 18. CRYER, P. E., Plasma norepinephrine and epinephrine in acromegaly, J Clin Endocrinol Metab 41: 542, 1975. 19. BROWN, G. M., P. E. GARFINKEL, J. J. WARSH, AND H. C.
STANCER, Effect of carbidopa on prolactin, growth hormone and cortisol secretion in man, J Clin Endocrinol Metab 43: 236, 1976. 20. HOKFELT, T., K. FUXE, AND M. GOLDSTEIN, Immunohisto-
References 1. CHIODINI, P. G., A. LIUZZI, L. BOTALLA, G. CREMASCOLI, AND
F. SILVESTRINI, Inhibitory effect of dopaminergic stimulation on growth hormone release in acromegaly, J Clin Endocrinol Metab 38: 200, 1974. 2. LIUZZI, A., P. G. CHIODINI, L. BOTALLA, G. CREMASCOLI, E.
r
E. MiiLLER, AND F. SILVESTRINI, Decreased plasma growth hormone (GH) levels in acromegalics following CB 154 (2-Bra-ergocryptine) administration, J Clin Endocrinol Metab 38: 910, 1974. 3. CAMANNI, F., F. MASSARA, L. BELFORTE, AND G. M. MOLI-
chemical localization of aromatic L-amino acid decarboxylase (dopa decarboxylase) in central dopamine and 5-hydroxytryptamine nerve cell bodies in the rat, Brain Res 53: 175, 1973. 21. LOTTI, V. J., AND C. C. PORTER, Potentiation and inhibition of some central actions of L-dopa by decarboxylase inhibitors, J Pharmacol Exp Ther 172: 406, 1970. 22. PtJHRINGER, W., A. WIRZ-JUSTICE, AND I. LANCRANJAN, Mood elevation and pituitary stimulation after iv 1-5-HTP in normal subjects: evidence for a common serotoninergic mechanism, Neurosci Lett 2: 349, 1976. 23. BROADWELL, R. D., AND M. W. BRIGHTMAN, Entry of peroxidase in neurons of the central and peripheral nervous system
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 19:34 For personal use only. No other uses without permission. . All rights reserved.
652
CAMANNI ET AL.
JCE&M . 1978 Vol47 • No 3 W
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