Effect of Bromoergocriptine on TRH-Induced Growth Hormone and Prolactin Release in Acromegalic Patients MIYUKI ISHIBASHI, TOHRU YAMAJI, AND KINORI KOSAKA The Third Department Hongo, Tokyo, Japan
of Internal
Medicine, Faculty of Medicine, University of Tokyo,
ABSTRACT. In an attempt to evaluate the dynamics of growth hormone (GH) and prolactin secretion in acromegalic patients, the response of serum GH as well as prolactin to 2-bromo-a-ergocriptine (CB154) alone or to CB154 combined with thyrotropin-releasing hormone (TRH) was studied in 8 subjects with this disease. Oral administration of CB154 unequivocally decreased serum prolactin levels in all of the 8 patients, while GH-inhibitory action of the drug was observed only in 6 subjects who responded to TRH with secretion of GH. The response of serum GH to TRH was not
B
qualitatively and quantitatively altered by the treatment of patients with CB154 in a daily dose of 5 mg for two weeks. This treatment, on the other hand, remarkably suppressed basal levels of prolactin and completely blocked TRH-induced prolactin release in all of the subjects. The results suggest that there exists a dissociation between GH and prolactin responses to CB154 in acromegalic patients, and that CB154 and TRH may not share a common site of action on GH release in this pathologic state. (J Clin Endocrinol Metab 45: 275, 1977)
ROMOERGOCRIPTINE (CB154) is known to suppress prolactin secretion in normal subjects as well as in patients with prolactin-secreting tumors, probably acting at the pituitary lactotroph (1-4). Recently, this ergot alkaloid has been shown to lower the circulating levels of GH in patients with active acromegaly and its use in the medical management of this disease has been proposed (5-8). The mechanism of action of CB154 on GH secretion in acromegalic patients, however, has not been established. This study was undertaken to evaluate the inhibitory action of CB154 on both GH and prolactin secretion in active acromegalic patients.
in the morning after an overnight fast. The patients were kept in a recumbent position for at least 1 h before and throughout the study except for standing to void. Blood samples were collected through an indwelling catheter placed in an antecubital vein. TRH test After taking the control sample, 500 /zg of synthetic TRH was injected iv as a single bolus. The details of the blood sampling and the test procedures were described elsewhere (9,10). Seven patients were given 5 mg of CB154 daily for two consecutive weeks and, in addition, a 2.5 mg dose 2 h prior to the second TRH test. CB154 administration
After two baseline blood samples were taken (-30 and 0 min), 5 mg of CB154 (Sandoz, Subjects Basel) was administered orally and blood specimens were collected at 30-min intervals for 4 h. Eight acromegalic patients (5 females and 3 Serum GH and prolactin responses to acute males), aged between 20 and 46, were studied. CB154 administration were arbitrarily defined as All patients exhibited physical features of positive when a decrease of at least 50% below acromegaly, elevated baseline serum GH conthe mean of the baseline values was achieved. centrations and failure of the serum GH levels to suppress during an oral glucose tolerance Radioimmunoassays test. None of the subjects received any medication which has been shown to affect GH or Serum was separated by centrifugation and prolactin secretion. All studies were performed stored at - 2 0 C until assayed. Double antibody radioimmunoassays, previously described in detail (9), were used to determine the concenReceived November 2, 1976. Materials and Methods
275
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istration of CB154 in 8 acromegalic patients. The results are expressed as the per cent of the mean basal values. Six (#1-5, #8) out of eight subjects exhibited a significant decrease (50% or more of the basal levels) in serum GH concentrations at 90 to 180 min after the administration, while CB154 failed to suppress circulating GH levels in 2 cases (#6 and #7). Prolactin response was even more pronounced than that of GH (Fig. 2); serum prolactin levels were decreased to less than 30% of the control values in all of the patients including two subjects (#6 and #7), in whom CB154 was ineffective in decreasing serum GH concentrations.
160 150 140 130 120 110 100 90 80 70 60 50 40
TRH-induced GH and prolactin release before and after CB154 treatment
30 20 10 0 -30
0
30
60
90
120
150
180
210
240
TIME IN MINUTES
FIG. 1. Changes of serum GH concentrations in 8 acromegalic patients following the oral administration of 5 mg of CB154. Solid lines indicate the responders, and dotted lines the non-responders.
Figure 3 shows serum GH responses to iv injection of TRH in 7 patients before and after the administration of CB154 for two weeks. TRH induced GH release in 5 pano 120 110
trations of GH and prolactin. The materials for radioimmunoassays were kindly donated by the National Institute of Arthritis, Metabolism, and Digestive Diseases and the National Pituitary Agency. The lower limits of sensitivities were 0.3 ng/ml for GH and 1.0 ng/ml for prolactin. The coefficients of variation for GH averaged 5.3% for intra-assay error and 9.6% for interassay error, while they were estimated to be 7.4% and 8.2%, respectively, for prolactin.
100
90 80 70 60 50 40 30
Statistical analysis
20
Student's t test for paired data was used for statistical analysis.
10 0L -30
Results
Acute administration of CB154 In Fig. 1 are shown the changes of serum GH concentrations after the acute admin-
0
30
60
90
T I M E IN
120
150
180
210
240
MINUTES
FIG. 2. Changes of serum prolactin concentrations in 8 acromegalic patients following the oral administration of 5 mg of CB154. Note that all of the subjects responded to CB154 and that suppression of prolactin is more pronounced than that of GH.
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277
BROMOERGOCRIPTINE AND ACROMEGALY tients (#1-5) and their GH peaks ranged from 35.0 to 2,080 ng/ml (560 ± 383 ng/ml, mean ± SE) before treatment. Although CB154 administration resulted in a marked suppression of basal GH levels in these five cases (2.1-33% of the control), GH responses to TRH injection were not inhibited. The peak GH concentrations after the treatment ranged from 31.2 to 3,400 ng/ ml (777 ± 656 ng/ml, mean ± SE), and no significant difference was obtained between the mean peak values before and after CB154 administration. In the remaining two patients (#6 and #7) who did not respond to TRH, their basal GH concentrations
0
15 30
60
90 120
90
120
TRH
#6
0
15 30
60
0
15 30
-60
140 120 100 80 60
0
40
TRH I
15 30
60
90 120
90 120
20 pre-treatment
0 0 15 30
3.500
60
90 120
post-treatment
#6
TRH
3,000 2.500 2.000 1,500
0
1.000
15 30
60
90 120
TIME IN MINUTES
500 0
O 15 30
350
60
90 120 * ?
TRH
300 250 200
FIG. 4. Responses of serum prolactin levels to iv
injection of TRH at 0 time in 7 acromegalic patients before and after the treatment with CB154 (5 mg daily for two weeks). Note the dissociation between GH (Fig. 3) and prolactin responses.
150 100 50 0 15 30
60 90
120
pre-treatment post-treatment
0 15 30
60
90 120
TIME IN MINUTES
FIG. 3. Responses of serum GH levels to iv injection of TRH at 0 time in 7 acromegalic patients before and after the treatment with CB154 (5 mg daily for two weeks). Note that TRH-induced GH release after the treatment is similar as in the control period.
after CB154 treatment were lower than in the control study (Fig. 3); however, they were judged to be nonresponders to CB154, since the changes were within the ranges of day-to-day variations of their serum GH levels. Day-to-day variations ranged from 32.5 to 68.0 ng/ml (46.8 ± 9.5 ng/ml, mean ± SD, n = 12) and from 8.0 to 12.5 ng/ml (10.5 ± 2.0 ng/ml, mean ± SD, n = 4) in these subjects, respectively. Figure 4 depicts the prolactin responses to TRH injection before and after CB154 treatment. TRH-induced prolactin release as well as its basal levels were completely
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278
ISHIBASHI, YAMAJI AND KOSAKA
JCE & M • 1977 Vol 45 • No 2
inhibited by CB154 administration in all of the 7 subjects studied.
CB154 cannot overcome TRH-induced GH release renders it unlikely, though not impossible, that TRH and CB154 may share a common site of action. Discussion TRH-induced prolactin secretion was The foregoing results clearly show that completely blocked in all of the seven pathere exists a dissociation between the tients after CB154 treatment. A similar response of GH and that of prolactin to phenomenon has been observed in patients CB154 in active acromegalic patients. Acute with galactorrhea and amenorrhea synadministration of CB154 precipitously de- dromes including patients with prolactincreased the serum prolactin concentrations producing tumors (3,4). An in vitro study in all of the 8 acromegalic subjects studied, suggests that TRH stimulates prolactin rewhile the GH-inhibitory action of CB154 lease by a direct action on the pituitary was observed only in 6 patients. This (14). Based on this observation, it was condiscrepancy between GH and prolactin re- cluded that the suppressive effect of CB154 sponses to CB154 was more definitely dem- on prolactin release in acromegalic patients onstrated after long-term treatment with may be exerted at the pituitary level interthis drug. The administration of CB154 in acting with TRH. Concerning the curious a daily dose of 5 mg for two weeks un- dissociation between GH and prolactin inequivocally suppressed the circulating hibition by CB154 in active acromegalics levels of prolactin to less than 1 ng/ml, obtained in this study, two possibilities whereas plasma GH concentrations were might be considered. One is that circulating lowered in 5 patients who responded to prolactin in these patients originates from the acute administration of CB154. It was the normal pituitary tissue, and that adeconcluded that there exist two types of GH noma cells and normal pituitary cells reresponses to CB154 in active acromegaly; spond to CB154 in different ways. Another however, the prolactin responses are uni- possibility is that pituitary adenomas of acromegalics consist of two different cell formly normal. Of interest in this context types, GH-producing cells and prolactinis the close relationship between the resecreting cells, and that each kind responses of GH to CB154 and to TRH in sponds to CB154 in a different manner. acromegalic patients, which is consistent Judging from the normal prolactin levels with the observation of Liuzzi et al. (11). in our acromegalic patient except one (#6) Luteinizing hormone-releasing hormone who showed a slightly higher serum con(LH-RH) has been also shown to stimulate centration of prolactin than normal control GH secretion in some patients with acro- (10), the former view might be more likely. megaly (12,13). The effectiveness of LH-RH However, prolactin responses to TRH can in triggering GH release was not correlated be observed in vitro in pituitary adenoma with the GH-inhibitory action of CB154 in cells, which were obtained from the acroour 8 acromegalic patients. megalic patients with normo-prolactinemia The treatment of patients with CB154 (15). Being consonant with this finding, for two weeks failed to alter the response morphological examinations identified mamof GH to TRH administration. This is not mosomatotrophic tumors in patients whose due to the limited duration of CB154 prolactin levels were not elevated (16,17). treatment, since three subjects who had re- In the light of these findings, the second ceived the drug for 2 to 12 months al- possibility could not be ruled out. In any ways responded to TRH in a similar man- event, the present study indicates that there ner as in the control study, although their exists a dissociation between GH and probasal serum GH levels were suppressed to lactin responses to CB154 in patients with nearly normal value. The present result that acromegaly.
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BROMOERGOCRIPTINE AND ACROMEGALY Acknowledgments The authors are indebted to Dr. W. von Orelli, Sandoz Ltd., Basel, Switzerland, for the gift of CB154.
References 1. Lutterbeck, P. M., J. S. Pryor, L. Varga, and R. Wenner, Treatment of non-puerperal galactorrhoea with an ergot alkaloid, Br MedJ 3: 228, 1971. 2. Besser, G. M., L. Parke, C. R. W. Edwards, I. A. Forsyth, and A. S. McNeilly, Galactorrhoea: Successful treatment with reduction of prolactin levels by bromoergocryptine, Br Med J 3: 669, 1972. 3. Del Pozo, E., L. Varga, H. Wyss, G. Tolis, H. Friesen, R. Wenner, L. Vetter, and A. Uettwiler, Clinical and hormonal response to bromocriptin (CB154) in the galactorrhea syndromes, J Clin Endocrinol Metab 39: 18, 1974. 4. Hirvonen, E., T. Ranta, and M. Seppala, Prolactin and thyrotropin responses to throtropinreleasing hormone in patients with secondary amenorrhea: The effect of bromocriptine, J Clin Endocrinol Metab 42: 1024, 1976. 5. Liuzzi, A., P. G. Chiodini, L. Botalla, G. Cremascoli, E. E. Miiller, and F. Silvestrini, Decreased plasma growth hormone (GH) levels in acromegalics following CB154 (2-Br-a-ergocryptine) administration, J Clin Endocrinol Metab 38: 910, 1974. 6. Thorner, M. O., A. Chait, M. Aitken, G. Benker, S. R. Bloom, C. H. Mortimer, P. Sanders, A. Stuart-Mason, and G. M. Besser, Bromocriptine treatment of acromegaly, Br MedJ 1: 299, 1975. 7. Camanni, F., F. Massara, L. Belforte, and G. M. Molinatti, Changes in plasma growth hormone levels in normal and acromegalic subjects following administration of 2-bromo-a-ergocryptine, / Clin Endocrinol Metab 40: 363, 1975. 8. Sachdev, Y., A. Gomez-pan, W. M. G. Turnbridge, A. Duns, D. R. Weightman, R. Hall, and S. K. Goolamali, Bromocriptine therapy in acromegaly, Lancet 2: 1164, 1975.
279
9. Yamaji, T., Modulation of prolactin release by altered levels of thyroid hormones, Metabolism 23: 745, 1974. 10. Yamaji, T., K. Shimamoto, M. Ishibashi, K. Kosaka, and H. Orimo, Effect of age and sex on circulating and pituitary prolactin levels in human, Ada Endocrinol (Kbh) 83: 711, 1976. 11. Liuzzi, A., P. G. Chiodini, L. Botalla, F. Silvestrini, and E. E. Miiller, Growth hormone (GH)releasing activity of TRH and GH-lowering effect of dopaminergic drugs in acromegaly: Homogeneity in the two responses, J Clin Endocrinol Metab 39: 871, 1974. 12. Rubin, A. L., S. R. Levin, R. I. Bernstein, J. B. Tyrrell, C. Noacco, and P. H. Forsham, Stimulation of growth hormone by luteinizing hormonereleasing hormone in active acromegaly, / Clin Endocrinol Metab 37: 160, 1973. 13. Faglia, G., P. Beck-Peccoz, P. Travaglini, A. Paracchi, A. Spada, and A. Lewin, Elevation in plasma growth hormone concentration after luteinizing hormone-releasing hormone (LRH) in patients with active acromegaly, / Clin Endocrinol Metab 37: 338, 1973. 14. Tashjian, A. H. Jr., N. J. Barowsky, and D. K. Jensen, Thyrotropin releasing hormone: Direct evidence for stimulation of prolactin production by pituitary cells in culture, Biochem Biophys Res Commun 43: 516, 1971. 15. Ishibashi, M., and T. Yamaji, TRH-induced GH and prolactin release by eosinophilic pituitary adenoma in an in vitro flowing system, Abstracts of the American Endocrine Society, 57th Annual Meeting, New York, June 18-20, 1975, p. 255. 16. Zimmerman, E. A., R. Defending and A. G. Frantz, Prolactin and growth hormone in patients with pituitary adenomas: A correlative study of hormone in tumor and plasma by immunoperoxidase technique and radioimmunoassay, J Clin Endocrinol Metab 38: 577, 1974. 17. Corenblum, B., A. M. T. Sirek, E. Horvath, K. Kovacs, and C. Ezrin, Human mixed somatotrophic and lactotrophic pituitary adenomas, J Clin Endocrinol Metab 42: 857, 1976.
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of Internal
Medicine, Faculty of Medicine, University of Tokyo,
ABSTRACT. In an attempt to evaluate the dynamics of growth hormone (GH) and prolactin secretion in acromegalic patients, the response of serum GH as well as prolactin to 2-bromo-a-ergocriptine (CB154) alone or to CB154 combined with thyrotropin-releasing hormone (TRH) was studied in 8 subjects with this disease. Oral administration of CB154 unequivocally decreased serum prolactin levels in all of the 8 patients, while GH-inhibitory action of the drug was observed only in 6 subjects who responded to TRH with secretion of GH. The response of serum GH to TRH was not
B
qualitatively and quantitatively altered by the treatment of patients with CB154 in a daily dose of 5 mg for two weeks. This treatment, on the other hand, remarkably suppressed basal levels of prolactin and completely blocked TRH-induced prolactin release in all of the subjects. The results suggest that there exists a dissociation between GH and prolactin responses to CB154 in acromegalic patients, and that CB154 and TRH may not share a common site of action on GH release in this pathologic state. (J Clin Endocrinol Metab 45: 275, 1977)
ROMOERGOCRIPTINE (CB154) is known to suppress prolactin secretion in normal subjects as well as in patients with prolactin-secreting tumors, probably acting at the pituitary lactotroph (1-4). Recently, this ergot alkaloid has been shown to lower the circulating levels of GH in patients with active acromegaly and its use in the medical management of this disease has been proposed (5-8). The mechanism of action of CB154 on GH secretion in acromegalic patients, however, has not been established. This study was undertaken to evaluate the inhibitory action of CB154 on both GH and prolactin secretion in active acromegalic patients.
in the morning after an overnight fast. The patients were kept in a recumbent position for at least 1 h before and throughout the study except for standing to void. Blood samples were collected through an indwelling catheter placed in an antecubital vein. TRH test After taking the control sample, 500 /zg of synthetic TRH was injected iv as a single bolus. The details of the blood sampling and the test procedures were described elsewhere (9,10). Seven patients were given 5 mg of CB154 daily for two consecutive weeks and, in addition, a 2.5 mg dose 2 h prior to the second TRH test. CB154 administration
After two baseline blood samples were taken (-30 and 0 min), 5 mg of CB154 (Sandoz, Subjects Basel) was administered orally and blood specimens were collected at 30-min intervals for 4 h. Eight acromegalic patients (5 females and 3 Serum GH and prolactin responses to acute males), aged between 20 and 46, were studied. CB154 administration were arbitrarily defined as All patients exhibited physical features of positive when a decrease of at least 50% below acromegaly, elevated baseline serum GH conthe mean of the baseline values was achieved. centrations and failure of the serum GH levels to suppress during an oral glucose tolerance Radioimmunoassays test. None of the subjects received any medication which has been shown to affect GH or Serum was separated by centrifugation and prolactin secretion. All studies were performed stored at - 2 0 C until assayed. Double antibody radioimmunoassays, previously described in detail (9), were used to determine the concenReceived November 2, 1976. Materials and Methods
275
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276
JCE & M • 1977 Vol 45 • No 2
ISHIBASHI, YAMAJI AND KOSAKA
istration of CB154 in 8 acromegalic patients. The results are expressed as the per cent of the mean basal values. Six (#1-5, #8) out of eight subjects exhibited a significant decrease (50% or more of the basal levels) in serum GH concentrations at 90 to 180 min after the administration, while CB154 failed to suppress circulating GH levels in 2 cases (#6 and #7). Prolactin response was even more pronounced than that of GH (Fig. 2); serum prolactin levels were decreased to less than 30% of the control values in all of the patients including two subjects (#6 and #7), in whom CB154 was ineffective in decreasing serum GH concentrations.
160 150 140 130 120 110 100 90 80 70 60 50 40
TRH-induced GH and prolactin release before and after CB154 treatment
30 20 10 0 -30
0
30
60
90
120
150
180
210
240
TIME IN MINUTES
FIG. 1. Changes of serum GH concentrations in 8 acromegalic patients following the oral administration of 5 mg of CB154. Solid lines indicate the responders, and dotted lines the non-responders.
Figure 3 shows serum GH responses to iv injection of TRH in 7 patients before and after the administration of CB154 for two weeks. TRH induced GH release in 5 pano 120 110
trations of GH and prolactin. The materials for radioimmunoassays were kindly donated by the National Institute of Arthritis, Metabolism, and Digestive Diseases and the National Pituitary Agency. The lower limits of sensitivities were 0.3 ng/ml for GH and 1.0 ng/ml for prolactin. The coefficients of variation for GH averaged 5.3% for intra-assay error and 9.6% for interassay error, while they were estimated to be 7.4% and 8.2%, respectively, for prolactin.
100
90 80 70 60 50 40 30
Statistical analysis
20
Student's t test for paired data was used for statistical analysis.
10 0L -30
Results
Acute administration of CB154 In Fig. 1 are shown the changes of serum GH concentrations after the acute admin-
0
30
60
90
T I M E IN
120
150
180
210
240
MINUTES
FIG. 2. Changes of serum prolactin concentrations in 8 acromegalic patients following the oral administration of 5 mg of CB154. Note that all of the subjects responded to CB154 and that suppression of prolactin is more pronounced than that of GH.
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277
BROMOERGOCRIPTINE AND ACROMEGALY tients (#1-5) and their GH peaks ranged from 35.0 to 2,080 ng/ml (560 ± 383 ng/ml, mean ± SE) before treatment. Although CB154 administration resulted in a marked suppression of basal GH levels in these five cases (2.1-33% of the control), GH responses to TRH injection were not inhibited. The peak GH concentrations after the treatment ranged from 31.2 to 3,400 ng/ ml (777 ± 656 ng/ml, mean ± SE), and no significant difference was obtained between the mean peak values before and after CB154 administration. In the remaining two patients (#6 and #7) who did not respond to TRH, their basal GH concentrations
0
15 30
60
90 120
90
120
TRH
#6
0
15 30
60
0
15 30
-60
140 120 100 80 60
0
40
TRH I
15 30
60
90 120
90 120
20 pre-treatment
0 0 15 30
3.500
60
90 120
post-treatment
#6
TRH
3,000 2.500 2.000 1,500
0
1.000
15 30
60
90 120
TIME IN MINUTES
500 0
O 15 30
350
60
90 120 * ?
TRH
300 250 200
FIG. 4. Responses of serum prolactin levels to iv
injection of TRH at 0 time in 7 acromegalic patients before and after the treatment with CB154 (5 mg daily for two weeks). Note the dissociation between GH (Fig. 3) and prolactin responses.
150 100 50 0 15 30
60 90
120
pre-treatment post-treatment
0 15 30
60
90 120
TIME IN MINUTES
FIG. 3. Responses of serum GH levels to iv injection of TRH at 0 time in 7 acromegalic patients before and after the treatment with CB154 (5 mg daily for two weeks). Note that TRH-induced GH release after the treatment is similar as in the control period.
after CB154 treatment were lower than in the control study (Fig. 3); however, they were judged to be nonresponders to CB154, since the changes were within the ranges of day-to-day variations of their serum GH levels. Day-to-day variations ranged from 32.5 to 68.0 ng/ml (46.8 ± 9.5 ng/ml, mean ± SD, n = 12) and from 8.0 to 12.5 ng/ml (10.5 ± 2.0 ng/ml, mean ± SD, n = 4) in these subjects, respectively. Figure 4 depicts the prolactin responses to TRH injection before and after CB154 treatment. TRH-induced prolactin release as well as its basal levels were completely
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JCE & M • 1977 Vol 45 • No 2
inhibited by CB154 administration in all of the 7 subjects studied.
CB154 cannot overcome TRH-induced GH release renders it unlikely, though not impossible, that TRH and CB154 may share a common site of action. Discussion TRH-induced prolactin secretion was The foregoing results clearly show that completely blocked in all of the seven pathere exists a dissociation between the tients after CB154 treatment. A similar response of GH and that of prolactin to phenomenon has been observed in patients CB154 in active acromegalic patients. Acute with galactorrhea and amenorrhea synadministration of CB154 precipitously de- dromes including patients with prolactincreased the serum prolactin concentrations producing tumors (3,4). An in vitro study in all of the 8 acromegalic subjects studied, suggests that TRH stimulates prolactin rewhile the GH-inhibitory action of CB154 lease by a direct action on the pituitary was observed only in 6 patients. This (14). Based on this observation, it was condiscrepancy between GH and prolactin re- cluded that the suppressive effect of CB154 sponses to CB154 was more definitely dem- on prolactin release in acromegalic patients onstrated after long-term treatment with may be exerted at the pituitary level interthis drug. The administration of CB154 in acting with TRH. Concerning the curious a daily dose of 5 mg for two weeks un- dissociation between GH and prolactin inequivocally suppressed the circulating hibition by CB154 in active acromegalics levels of prolactin to less than 1 ng/ml, obtained in this study, two possibilities whereas plasma GH concentrations were might be considered. One is that circulating lowered in 5 patients who responded to prolactin in these patients originates from the acute administration of CB154. It was the normal pituitary tissue, and that adeconcluded that there exist two types of GH noma cells and normal pituitary cells reresponses to CB154 in active acromegaly; spond to CB154 in different ways. Another however, the prolactin responses are uni- possibility is that pituitary adenomas of acromegalics consist of two different cell formly normal. Of interest in this context types, GH-producing cells and prolactinis the close relationship between the resecreting cells, and that each kind responses of GH to CB154 and to TRH in sponds to CB154 in a different manner. acromegalic patients, which is consistent Judging from the normal prolactin levels with the observation of Liuzzi et al. (11). in our acromegalic patient except one (#6) Luteinizing hormone-releasing hormone who showed a slightly higher serum con(LH-RH) has been also shown to stimulate centration of prolactin than normal control GH secretion in some patients with acro- (10), the former view might be more likely. megaly (12,13). The effectiveness of LH-RH However, prolactin responses to TRH can in triggering GH release was not correlated be observed in vitro in pituitary adenoma with the GH-inhibitory action of CB154 in cells, which were obtained from the acroour 8 acromegalic patients. megalic patients with normo-prolactinemia The treatment of patients with CB154 (15). Being consonant with this finding, for two weeks failed to alter the response morphological examinations identified mamof GH to TRH administration. This is not mosomatotrophic tumors in patients whose due to the limited duration of CB154 prolactin levels were not elevated (16,17). treatment, since three subjects who had re- In the light of these findings, the second ceived the drug for 2 to 12 months al- possibility could not be ruled out. In any ways responded to TRH in a similar man- event, the present study indicates that there ner as in the control study, although their exists a dissociation between GH and probasal serum GH levels were suppressed to lactin responses to CB154 in patients with nearly normal value. The present result that acromegaly.
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BROMOERGOCRIPTINE AND ACROMEGALY Acknowledgments The authors are indebted to Dr. W. von Orelli, Sandoz Ltd., Basel, Switzerland, for the gift of CB154.
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