0021-972X/78/4702-0418$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society
Vol. 47, No. 2 Printed in U.S.A.
Induction of Growth Hormone and Prolactin Secretion by Luteinizing Hormone-Releasing Hormone and Its Blockade by Bromoergocriptine in Acromegalic Patients MIYUKI ISHIBASHI,* TOHRU YAMAJI, AND KINORI KOSAKA Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Tokyo, Japan ABSTRACT. In an attempt to evaluate the effect of LRH on GH and PRL secretion, LRH in a dose of 100 jag was injected iv to 22 patients with active acromegaly. A definite increase in both serum GH and PRL levels was observed in one patient, while four other subjects responded to LRH to secrete either GH or PRL. The effectiveness of LRH on GH and PRL release was not correlated with the age or sex of patients, the basal levels of serum GH or PRL, the GH response to TRH
L
UTEINIZING hormone-releasing hormone (LRH) is known to possess a stimulatory effect on GH secretion in some patients with active acromegaly (1, 2). Recently, it was demonstrated that LRH likewise elicits PRL release in this pathological condition (3). We have previously shown that GH and PRL secretion triggered by the administration of TRH could be dissociated by the pretreatment of the patients with 2-bromo-a-ergocriptine (CB154), suggesting the different sites of action of this drug to suppress GH and PRL secretion (4). The present study was undertaken 1) to assess the relationship of GH and PRL secretion by LRH administration, and 2) to examine the effect of CB154 on LRH-induced GH and PRL release in patients with acromegaly.
administration, or the increase in serum gonadotropin concentrations after LRH injection. In three patients, this LRH-induced GH and PRL release was completely blocked by pretreatment with 2-bromo-a-ergocriptine (CB154). The results suggest that elevations of GH and PRL after LRH occur rather sporadically in acromegalic patients and that the action of LRH on GH release is occasioned by a different mechanism from that of TRH. (J Clin Endocrinol Metab 47: 418, 1978)
cation which has been shown to affect GH or PRL secretion before the study. LRH administration
The patients were kept in a recumbent position for at least 1 h before and throughout the study, except for standing to void. LRH administration and blood sampling were done via an indwelling catheter placed in an antecubital vein. After taking the control sample, 100 /ig synthetic LRH (Tanabe Pharmaceutical Co., Japan) was injected iv as a single bolus. Blood samples were then collected at 15, 30, 60, 90, 120, and 180 min after the injection. No untoward reactions were observed after LRH administration in any of the subjects. Normal saline injection instead of LRH under exactly the same experimental conditions served as a control study in each patient. In three patients, the test was repeated after treatment with CB154; each received an oral dose of 2.5 mg CB154 (Sandoz, Basel, Switzerland) every Materials and Methods 12 h for 2 consecutive weeks and, in addition, a 2.5mg dose 2 h before the second LRH test. Serum Patients was separated by centrifugation and stored at -20 C Twenty-two acromegalic patients (8 men and 14 until assayed. women), aged 19-48 yr, were studied. All exhibited physical features of acromegaly, elevated baseline RIAs serum GH concentrations, and failure of the serum GH and PRL concentrations were determined by GH levels to suppress during an oral glucose tolerdouble antibody RIAs, previously described in deance test. None of the subjects received any meditail (4, 5). The materials for RIAs were kindly donated by the NIAMDD and the National PituiReceived August 9,1977. tary Agency. * To whom requests for reprints should be addressed. 418
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LRH ON GH AND PRL SECRETION
419
Results
injection of LRH in 22 patients with acromegaly. LRH induced GH release in three patients Fluctuations of GH and PRL in the control man and two women; patients 1, 4, and 5). (a study In these subjects, serum GH levels peaked at Changes in serum GH concentrations in 22 15 or 30 min after the injection and gradually acromegalic patients during the 3-h study pe- returned to the baseline by 90 min. Mean peak riods after the injection of normal saline values were 647% (patient 1), 260% (patient 4), ranged from 19.7-80.1% of their mean GH and 520% (patient 5) of their control levels, levels (48.2 ± 17.8%, mean ± SD). The varia- respectively. LRH administration was retion was fairly large; however, no sharp in- peated at least once on a separate day in these crease after the injection was observed in any patients and the GH responses again obtained. subject. Changes in serum PRL levels in the control study varied from 13.1-91.2% of their PRL responses to LRH administration averaged serum PRL concentrations (41.9 ± Figure 2 depicts serum PRL concentrations 26.2%, mean ± SD); and again, no consistent after LRH injection. A definite increase in pattern of serum PRL levels was demon- serum PRL levels was observed in three festrated. It was decided, therefore, that GH male subjects (patients 1, 2, and 3). Reproducand PRL responses were defined as positive ibility of the PRL responses to LRH in these when an increase of at least 100% of the base- patients was confirmed in at least two experiline value was obtained shortly after the LRH ments done on separate days. Serum PRL injection. peaked consistently at 15 min after the injection; their mean maximal levels were 247% (patient 1), 300% (patient 2), and 215% (paGH responses to LRH administration tient 3) of the baseline values, respectively. In Fig. 1 are shown GH responses to an iv T'
o male • o
LRH \OOfig
1.000
I
•
900
O-
female
LRH 100/'g
male female
60 r
I
-o r!2
800 700 600 500 400 300 200 100 90 80 70 60 50 40 30 20 10 -o
o--
60
90
0 0
15 30
60 TIME
90 IN
120
180
MINUTES
FIG. 1. Responses of serum GH levels to an iv injection of LRH at time zero in 22 acromegalic patients. , Responders; , nonresponders.
0
15 30
TIME
120 •
180
IN M I N U T E S
FIG. 2. Responses of serum PRL levels to an iv injection of LRH at time zero in 22 acromegalic patients. , Responders: , nonresponders.
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ISHIBASHI, YAMAJI, AND KOSAKA
420
failed to demonstrate such a definite and sharp rise in serum GH and PRL levels as was observed after the LRH administration. Second, the GH and PRL responses to LRH were reproducible in these patients. Finally, no untoward reactions to LRH injection were observed in any of the patients, and blood samples were taken using indwelling catheters. The present results are consistent with earlier observations (1-3); however, the number of the responders was far less, though a similar dose of LRH was injected and a similar criterion was employed to define the response as positive. The serum GH response to LRH seemed to be unrelated to that of PRL. LRH injection resulted in the elevation of serum levels of both GH and PRL in 1 of our 22 patients, while 4 other subjects secreted either GH or PRL in response to LRH administration. The response of GH and/or PRL to LRH was not apparently correlated with the sexes or ages of the patients or with the baseline levels of GH or PRL. It was unrelated to the serum GH response to TRH, as 2 (patients 2 and 5) out of 5 patients who responded to LRH to secrete GH or PRL were nonresponders to TRH. It has been suggested that the serum GH response to LRH might be linked to the functional state of the gonads of acromegalic patients (1). However, 3 of the subjects in the
Effect of CB154 treatment on LRH-induced GH and PRL release In Fig. 3 are illustrated serum GH and PRL responses to an iv injection of LRH in three patients (patients 1, 2, and 3) before and after the administration of CB154 for 2 weeks. LRH induced GH release in one of these patients (patient 1), and this response was completely blocked by the treatment with CB154. A decrease in basal GH levels was observed after CB154 administration in another subject (patient 3), although she did not respond to LRH to secrete GH. Patient 2 showed a gradual rise in serum GH concentrations after LRH injection before and after the treatment; however, she was judged to be a non-GH responder to both LRH and CB154, because a similar pattern of GH fluctuation was observed in the control study. Both basal PRL levels and LRH-induced PRL release were suppressed by CB154 administration in all of the three subjects studied. Discussion The foregoing results have shown that LRH evokes GH and PRL release in some patients with active acromegaly. That this was occasioned by nonspecific stress is unlikely for the following reasons. First, the control studies .LRH
,LRH
JCE&M • 1978 Vol 47 • No 2
LRH
#3
FIG. 3. Responses of serum GH and PRL levels to an iv injection of LRH at time zero in three responders before ( • • ) and after (O O) the treatment with CB154 (5 mg daily for 2 weeks). The results of two experiments conducted in each patient before CB154 administration are depicted separately. , Spontaneous fluctuations in GH and PRL levels in the control study. 180
0 15 30 60 90 120
180 '•
TIME
IN
MINUTES
0
••
01530 60 90 120
180
> Pre-treatment O Post-treatment -• Control
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 20 November 2015. at 17:16 For personal use only. No other uses without permission. . All rights reserved.
LRH ON GH AND PRL SECRETION
y
present study (patients 2, 3, and 5) showed normal responses of serum LH and FSH to LRH with normal gonadal function, whereas the rise in serum levels of gonadotropins after LRH injection was significantly decreased in the remaining 2 responders (patients 1 and 4). Of the 17 GH nonresponders, on the other hand, 9 had normal gonadotropin responses to LRH, while 8 other patients did not. It seems, therefore, that the responders of GH and/or PRL to LRH occur rather "sporadically" in acromegalic subjects. Administration of CB154 suppressed the basal levels of PRL and completely blocked LRH-induced PRL release in all of the three PRL responders to LRH. We have previously demonstrated that TRH-evoked PRL secretion was similarly inhibited by CB154 under the same experimental conditions (4). The site of the PRL inhibitory action of CB154 in acromegalic patients is unknown (4, 6). These results suggest, however, that LRH, TRH, and CB154 may share a common site of action on PRL release in this pathological condition. TRH-induced GH release in patients with acromegaly is not qualitatively and quantitatively influenced by CB154 administration (4). In contrast, CB154 in the present study effectively blocked LRH-triggered GH secretion in one acromegalic patient (patient 1). In this subject, CB154 failed to suppress GH release induced by TRH. If the suppressive effect of CB154 on GH secretion is mediated by a dopaminergic pathway (7, 8), LRH may act at a hypothalamic locus. Alternatively, the effect of LRH may be exerted at the pituitary or at the hypothalamic level if CB154 possesses a direct action on pituitary adenoma cells to
421
inhibit GH release (9). It may be concluded, in this patient, that the action of LRH on GH release is modulated by a different mechanism than that of TRH.
Acknowledgment The authors are indebted to Dr. W. von Orelli (Sandoz Ltd., Basel, Switzerland) for the gift of CB154.
References 1. RUBIN, A. L., S. R. LEVIN, R. I. BERNSTEIN, J. B. TYRRELL,
C. NOACCO, AND P. H. FORSHAM, Stimulation of growth
hormone by luteinizing hormone-releasing hormone in active acromegaly, J Clin Endocrinol Metab 37: 160,1973. 2. FAGLIA, G., P. BECK-PECCOZ, P. TRAVAGLINI, A. PARACCHI,
A. SPADA, AND A. LEWIN, Elevations in plasma growth hormone concentration after luteinizing hormone-releasing hormone (LRH) in patients with active acromegaly, J Clin Endocrinol Metab 37: 338, 1973. 3. CATANIA, A., L. CANTALAMESSA, AND E. RESCHINI, Plasma
prolactin response to luteinizing hormone-releasing hormone in acromegalic patients, J Clin Endocrinol Metab 43: 689, 1976. 4. ISHIBASHI, M., T. YAMAJI, AND K. KOSAKA, Effect of brom-
oergocriptine on TRH-induced growth hormone and prolactin release in acromegalic patients, J Clin Endocrinol Metab 45: 275, 1977. 5. YAMAJI, T., K. SHIMAMOTO, M. ISHIBASHI, K. KOSAKA, AND
H. ORIMO, Effect of age and sex on circulating and pituitary prolactin levels in human, Acta Endocrinol (Kbh) 83: 711, 1976. 6. CHIODINI, P. G., A. LIUZZI, E. E. MULLER, L. BOTALLA, C. CREMASCOLI, G. OPPIZZI, G. VERDE, AND F. SILVESTRINI,
Inhibitory effect of an ergoline derivative, methergoline, on growth hormone and prolactin levels in acromegalic patients, J Clin Endocrinol Metab 43: 356, 1976. 7. LIUZZI, A., P. G. CHIODINI, L. BOTALLA, G. CREMASCOLI, E.
E. MULLER, AND F. SILVESTRINI, Decreased plasma growth hormone (GH) levels in acromegalics following CB154 (2-Bra-ergocriptine) administration, J Clin Endocrinol Metab 38: 910, 1974. 8. LIUZZI, A., P. G. CHIODINI, L. BOTALLA, F. SILVESTRINI, AND
E. E. MULLER, 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. 9. CAMANNI, F., F. MASSARA, V. FASSIO, G. M. MOLINATTI, AND
E. E. MULLER, Effect of five dopaminergic drugs on plasma growth hormone levels in acromegalic subjects, Neuroendocrinology 19: 227, 1975.
.V
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Vol. 47, No. 2 Printed in U.S.A.
Induction of Growth Hormone and Prolactin Secretion by Luteinizing Hormone-Releasing Hormone and Its Blockade by Bromoergocriptine in Acromegalic Patients MIYUKI ISHIBASHI,* TOHRU YAMAJI, AND KINORI KOSAKA Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Tokyo, Japan ABSTRACT. In an attempt to evaluate the effect of LRH on GH and PRL secretion, LRH in a dose of 100 jag was injected iv to 22 patients with active acromegaly. A definite increase in both serum GH and PRL levels was observed in one patient, while four other subjects responded to LRH to secrete either GH or PRL. The effectiveness of LRH on GH and PRL release was not correlated with the age or sex of patients, the basal levels of serum GH or PRL, the GH response to TRH
L
UTEINIZING hormone-releasing hormone (LRH) is known to possess a stimulatory effect on GH secretion in some patients with active acromegaly (1, 2). Recently, it was demonstrated that LRH likewise elicits PRL release in this pathological condition (3). We have previously shown that GH and PRL secretion triggered by the administration of TRH could be dissociated by the pretreatment of the patients with 2-bromo-a-ergocriptine (CB154), suggesting the different sites of action of this drug to suppress GH and PRL secretion (4). The present study was undertaken 1) to assess the relationship of GH and PRL secretion by LRH administration, and 2) to examine the effect of CB154 on LRH-induced GH and PRL release in patients with acromegaly.
administration, or the increase in serum gonadotropin concentrations after LRH injection. In three patients, this LRH-induced GH and PRL release was completely blocked by pretreatment with 2-bromo-a-ergocriptine (CB154). The results suggest that elevations of GH and PRL after LRH occur rather sporadically in acromegalic patients and that the action of LRH on GH release is occasioned by a different mechanism from that of TRH. (J Clin Endocrinol Metab 47: 418, 1978)
cation which has been shown to affect GH or PRL secretion before the study. LRH administration
The patients were kept in a recumbent position for at least 1 h before and throughout the study, except for standing to void. LRH administration and blood sampling were done via an indwelling catheter placed in an antecubital vein. After taking the control sample, 100 /ig synthetic LRH (Tanabe Pharmaceutical Co., Japan) was injected iv as a single bolus. Blood samples were then collected at 15, 30, 60, 90, 120, and 180 min after the injection. No untoward reactions were observed after LRH administration in any of the subjects. Normal saline injection instead of LRH under exactly the same experimental conditions served as a control study in each patient. In three patients, the test was repeated after treatment with CB154; each received an oral dose of 2.5 mg CB154 (Sandoz, Basel, Switzerland) every Materials and Methods 12 h for 2 consecutive weeks and, in addition, a 2.5mg dose 2 h before the second LRH test. Serum Patients was separated by centrifugation and stored at -20 C Twenty-two acromegalic patients (8 men and 14 until assayed. women), aged 19-48 yr, were studied. All exhibited physical features of acromegaly, elevated baseline RIAs serum GH concentrations, and failure of the serum GH and PRL concentrations were determined by GH levels to suppress during an oral glucose tolerdouble antibody RIAs, previously described in deance test. None of the subjects received any meditail (4, 5). The materials for RIAs were kindly donated by the NIAMDD and the National PituiReceived August 9,1977. tary Agency. * To whom requests for reprints should be addressed. 418
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LRH ON GH AND PRL SECRETION
419
Results
injection of LRH in 22 patients with acromegaly. LRH induced GH release in three patients Fluctuations of GH and PRL in the control man and two women; patients 1, 4, and 5). (a study In these subjects, serum GH levels peaked at Changes in serum GH concentrations in 22 15 or 30 min after the injection and gradually acromegalic patients during the 3-h study pe- returned to the baseline by 90 min. Mean peak riods after the injection of normal saline values were 647% (patient 1), 260% (patient 4), ranged from 19.7-80.1% of their mean GH and 520% (patient 5) of their control levels, levels (48.2 ± 17.8%, mean ± SD). The varia- respectively. LRH administration was retion was fairly large; however, no sharp in- peated at least once on a separate day in these crease after the injection was observed in any patients and the GH responses again obtained. subject. Changes in serum PRL levels in the control study varied from 13.1-91.2% of their PRL responses to LRH administration averaged serum PRL concentrations (41.9 ± Figure 2 depicts serum PRL concentrations 26.2%, mean ± SD); and again, no consistent after LRH injection. A definite increase in pattern of serum PRL levels was demon- serum PRL levels was observed in three festrated. It was decided, therefore, that GH male subjects (patients 1, 2, and 3). Reproducand PRL responses were defined as positive ibility of the PRL responses to LRH in these when an increase of at least 100% of the base- patients was confirmed in at least two experiline value was obtained shortly after the LRH ments done on separate days. Serum PRL injection. peaked consistently at 15 min after the injection; their mean maximal levels were 247% (patient 1), 300% (patient 2), and 215% (paGH responses to LRH administration tient 3) of the baseline values, respectively. In Fig. 1 are shown GH responses to an iv T'
o male • o
LRH \OOfig
1.000
I
•
900
O-
female
LRH 100/'g
male female
60 r
I
-o r!2
800 700 600 500 400 300 200 100 90 80 70 60 50 40 30 20 10 -o
o--
60
90
0 0
15 30
60 TIME
90 IN
120
180
MINUTES
FIG. 1. Responses of serum GH levels to an iv injection of LRH at time zero in 22 acromegalic patients. , Responders; , nonresponders.
0
15 30
TIME
120 •
180
IN M I N U T E S
FIG. 2. Responses of serum PRL levels to an iv injection of LRH at time zero in 22 acromegalic patients. , Responders: , nonresponders.
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ISHIBASHI, YAMAJI, AND KOSAKA
420
failed to demonstrate such a definite and sharp rise in serum GH and PRL levels as was observed after the LRH administration. Second, the GH and PRL responses to LRH were reproducible in these patients. Finally, no untoward reactions to LRH injection were observed in any of the patients, and blood samples were taken using indwelling catheters. The present results are consistent with earlier observations (1-3); however, the number of the responders was far less, though a similar dose of LRH was injected and a similar criterion was employed to define the response as positive. The serum GH response to LRH seemed to be unrelated to that of PRL. LRH injection resulted in the elevation of serum levels of both GH and PRL in 1 of our 22 patients, while 4 other subjects secreted either GH or PRL in response to LRH administration. The response of GH and/or PRL to LRH was not apparently correlated with the sexes or ages of the patients or with the baseline levels of GH or PRL. It was unrelated to the serum GH response to TRH, as 2 (patients 2 and 5) out of 5 patients who responded to LRH to secrete GH or PRL were nonresponders to TRH. It has been suggested that the serum GH response to LRH might be linked to the functional state of the gonads of acromegalic patients (1). However, 3 of the subjects in the
Effect of CB154 treatment on LRH-induced GH and PRL release In Fig. 3 are illustrated serum GH and PRL responses to an iv injection of LRH in three patients (patients 1, 2, and 3) before and after the administration of CB154 for 2 weeks. LRH induced GH release in one of these patients (patient 1), and this response was completely blocked by the treatment with CB154. A decrease in basal GH levels was observed after CB154 administration in another subject (patient 3), although she did not respond to LRH to secrete GH. Patient 2 showed a gradual rise in serum GH concentrations after LRH injection before and after the treatment; however, she was judged to be a non-GH responder to both LRH and CB154, because a similar pattern of GH fluctuation was observed in the control study. Both basal PRL levels and LRH-induced PRL release were suppressed by CB154 administration in all of the three subjects studied. Discussion The foregoing results have shown that LRH evokes GH and PRL release in some patients with active acromegaly. That this was occasioned by nonspecific stress is unlikely for the following reasons. First, the control studies .LRH
,LRH
JCE&M • 1978 Vol 47 • No 2
LRH
#3
FIG. 3. Responses of serum GH and PRL levels to an iv injection of LRH at time zero in three responders before ( • • ) and after (O O) the treatment with CB154 (5 mg daily for 2 weeks). The results of two experiments conducted in each patient before CB154 administration are depicted separately. , Spontaneous fluctuations in GH and PRL levels in the control study. 180
0 15 30 60 90 120
180 '•
TIME
IN
MINUTES
0
••
01530 60 90 120
180
> Pre-treatment O Post-treatment -• Control
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 20 November 2015. at 17:16 For personal use only. No other uses without permission. . All rights reserved.
LRH ON GH AND PRL SECRETION
y
present study (patients 2, 3, and 5) showed normal responses of serum LH and FSH to LRH with normal gonadal function, whereas the rise in serum levels of gonadotropins after LRH injection was significantly decreased in the remaining 2 responders (patients 1 and 4). Of the 17 GH nonresponders, on the other hand, 9 had normal gonadotropin responses to LRH, while 8 other patients did not. It seems, therefore, that the responders of GH and/or PRL to LRH occur rather "sporadically" in acromegalic subjects. Administration of CB154 suppressed the basal levels of PRL and completely blocked LRH-induced PRL release in all of the three PRL responders to LRH. We have previously demonstrated that TRH-evoked PRL secretion was similarly inhibited by CB154 under the same experimental conditions (4). The site of the PRL inhibitory action of CB154 in acromegalic patients is unknown (4, 6). These results suggest, however, that LRH, TRH, and CB154 may share a common site of action on PRL release in this pathological condition. TRH-induced GH release in patients with acromegaly is not qualitatively and quantitatively influenced by CB154 administration (4). In contrast, CB154 in the present study effectively blocked LRH-triggered GH secretion in one acromegalic patient (patient 1). In this subject, CB154 failed to suppress GH release induced by TRH. If the suppressive effect of CB154 on GH secretion is mediated by a dopaminergic pathway (7, 8), LRH may act at a hypothalamic locus. Alternatively, the effect of LRH may be exerted at the pituitary or at the hypothalamic level if CB154 possesses a direct action on pituitary adenoma cells to
421
inhibit GH release (9). It may be concluded, in this patient, that the action of LRH on GH release is modulated by a different mechanism than that of TRH.
Acknowledgment The authors are indebted to Dr. W. von Orelli (Sandoz Ltd., Basel, Switzerland) for the gift of CB154.
References 1. RUBIN, A. L., S. R. LEVIN, R. I. BERNSTEIN, J. B. TYRRELL,
C. NOACCO, AND P. H. FORSHAM, Stimulation of growth
hormone by luteinizing hormone-releasing hormone in active acromegaly, J Clin Endocrinol Metab 37: 160,1973. 2. FAGLIA, G., P. BECK-PECCOZ, P. TRAVAGLINI, A. PARACCHI,
A. SPADA, AND A. LEWIN, Elevations in plasma growth hormone concentration after luteinizing hormone-releasing hormone (LRH) in patients with active acromegaly, J Clin Endocrinol Metab 37: 338, 1973. 3. CATANIA, A., L. CANTALAMESSA, AND E. RESCHINI, Plasma
prolactin response to luteinizing hormone-releasing hormone in acromegalic patients, J Clin Endocrinol Metab 43: 689, 1976. 4. ISHIBASHI, M., T. YAMAJI, AND K. KOSAKA, Effect of brom-
oergocriptine on TRH-induced growth hormone and prolactin release in acromegalic patients, J Clin Endocrinol Metab 45: 275, 1977. 5. YAMAJI, T., K. SHIMAMOTO, M. ISHIBASHI, K. KOSAKA, AND
H. ORIMO, Effect of age and sex on circulating and pituitary prolactin levels in human, Acta Endocrinol (Kbh) 83: 711, 1976. 6. CHIODINI, P. G., A. LIUZZI, E. E. MULLER, L. BOTALLA, C. CREMASCOLI, G. OPPIZZI, G. VERDE, AND F. SILVESTRINI,
Inhibitory effect of an ergoline derivative, methergoline, on growth hormone and prolactin levels in acromegalic patients, J Clin Endocrinol Metab 43: 356, 1976. 7. LIUZZI, A., P. G. CHIODINI, L. BOTALLA, G. CREMASCOLI, E.
E. MULLER, AND F. SILVESTRINI, Decreased plasma growth hormone (GH) levels in acromegalics following CB154 (2-Bra-ergocriptine) administration, J Clin Endocrinol Metab 38: 910, 1974. 8. LIUZZI, A., P. G. CHIODINI, L. BOTALLA, F. SILVESTRINI, AND
E. E. MULLER, 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. 9. CAMANNI, F., F. MASSARA, V. FASSIO, G. M. MOLINATTI, AND
E. E. MULLER, Effect of five dopaminergic drugs on plasma growth hormone levels in acromegalic subjects, Neuroendocrinology 19: 227, 1975.
.V
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