Apomorphine: Effect on Growth Hormone I. MAANY, A. FRAZER, AND J. MENDELS
Department of Psychiatry, University of Pennsylvania and Affective Diseases Research Unit, Veterans Administration Hospital, Philadelphia, Pennsylvania 19104 ABSTRACT. Apomorphine (0.75 mg SC) was found to elicit growth hormone release in normal men. The younger men had a significantly greater peak growth hormone response to apomorphine as compared to the older men. Among other possible
explanations, this finding may indicate that dopamine receptors in the hypothalamus are more sensitive to apomorphine in younger than in older men. (J Clin Endocrinol Metab 40: 162, 1975)
T is known that catecholamines are involved in the regulation of growth hormone (GH) release in mammals (1). However, the relative importance of norepinephrine (NE) and of dopamine (DA) in eliciting this release is controversial. A more central role for dopaminergic neurons (than for NE) is suggested by several lines of investigation including the presence of large quantities of dopamine in the external layer of the median eminence (2,3) and the close relationship of DA-containing granules to capillaries of the pituitary portal system (4). Further, GH is released in response to apomorphine (APO) administration (5). Several important features of apomorphine's mechanism of action deserve emphasis: 1) It appears that APO stimulates DA receptors directly; stored or newly synthesized DA does not appear to be needed for APO to produce its dopaminergic effects (6,7). 2) APO does not change the steady state concentration of brain NE, DA or serotonin (8,9). 3) APO appears to act specifically on dopamine receptors—it has little demonstrable effect on a NE-mediated response in the spinal cord (7) nor does it alter the turnover of brain NE, whereas the synthesis of brain DA appears to be reduced (7,8,10). Thus, it seems reasonable to conclude that the GH response elicited by APO is due primarily to stimulation of central dopaminergic receptors, probably at the level of the external layer of the median eminence.
effects of age on GH release in response to APO
I
We have been investigating the effect of apomorphine on GH release in groups of depressed patients (11,12). For control purposes, the effect of APO on GH release in normal subjects was examined. To our knowledge, the
Received May 17, 1974. Reprint requests to J. Mendels, M.D.
has not been reported. Materials and Methods Normal male volunteers were screened and any individual with diabetes, metabolic or other endocrine disorders or psychiatric illness were excluded from the study. Subjects were within 10% of their ideal body weight and drug-free for at least 1 month prior to the test. There was no history of psychiatric illness, especially depression, in their first-degree relatives. Group I ("Young"): Seven male college students ranging in age from 18 to 28 yr (21 ± 1; X ± SEM). Group II ("Older"): Nine males ranging in age from 36 to 58 yr (44 ± 2). All subjects were paid and informed consents were obtained. Following an overnight fast, an indwelling catheter was inserted into the antecubital vein and kept open with heparin-saline. Blood samples were obtained at 20-min intervals. Three base line samples were obtained before the administration of APO (0.75 mg SC), and samples were then collected over the next 140 min. The blood was then centrifuged and the serum stored at 20 C until assayed. GH concentration in the plasma was measured by a double antibody radioimmunoassay procedure utilizing 125I-HGH (New England Nuclear). Statistical evaluations were by Student's t test (13).
Results The younger subjects had a significantly greater peak GH response to APO as compared with the older subjects (Table 1). Peak responses occurred 40 to 60 min after drug administration. This difference in response between the two subject populations was not due to any difference in the mean weights of the two groups. The mean weight of the younger subjects was 169 ± 10 lb (X ± SEM), whereas the older subjects had a mean weight of 170 ± 9 lb. 162
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163
COMMENTS TABLE 1. Growth hormone response to apomorphine administration 'lasma growth hormone (ng/ml) +20
+40
+60
+80
+ 100
+ 120
+ 140
1.5 ± 0.2
2.4 ± 0.8
19.0 ± 3.7
19.7 ± 2.4
12.9 ± 3.1
7.2 ± 2.4
3.7 ± 1.2
2.4 ± 0.6
1.0 ± 0.04
1.0 ± 0.1
3.3 ± 0.8
9.0 ±1.4
10.8 ±1.0
7.3 ± 1 . 1
2.9 + 0.7
1.5 ± 0.2
1.3 ± 0.1
NS
NS
NS
Department of Psychiatry, University of Pennsylvania and Affective Diseases Research Unit, Veterans Administration Hospital, Philadelphia, Pennsylvania 19104 ABSTRACT. Apomorphine (0.75 mg SC) was found to elicit growth hormone release in normal men. The younger men had a significantly greater peak growth hormone response to apomorphine as compared to the older men. Among other possible
explanations, this finding may indicate that dopamine receptors in the hypothalamus are more sensitive to apomorphine in younger than in older men. (J Clin Endocrinol Metab 40: 162, 1975)
T is known that catecholamines are involved in the regulation of growth hormone (GH) release in mammals (1). However, the relative importance of norepinephrine (NE) and of dopamine (DA) in eliciting this release is controversial. A more central role for dopaminergic neurons (than for NE) is suggested by several lines of investigation including the presence of large quantities of dopamine in the external layer of the median eminence (2,3) and the close relationship of DA-containing granules to capillaries of the pituitary portal system (4). Further, GH is released in response to apomorphine (APO) administration (5). Several important features of apomorphine's mechanism of action deserve emphasis: 1) It appears that APO stimulates DA receptors directly; stored or newly synthesized DA does not appear to be needed for APO to produce its dopaminergic effects (6,7). 2) APO does not change the steady state concentration of brain NE, DA or serotonin (8,9). 3) APO appears to act specifically on dopamine receptors—it has little demonstrable effect on a NE-mediated response in the spinal cord (7) nor does it alter the turnover of brain NE, whereas the synthesis of brain DA appears to be reduced (7,8,10). Thus, it seems reasonable to conclude that the GH response elicited by APO is due primarily to stimulation of central dopaminergic receptors, probably at the level of the external layer of the median eminence.
effects of age on GH release in response to APO
I
We have been investigating the effect of apomorphine on GH release in groups of depressed patients (11,12). For control purposes, the effect of APO on GH release in normal subjects was examined. To our knowledge, the
Received May 17, 1974. Reprint requests to J. Mendels, M.D.
has not been reported. Materials and Methods Normal male volunteers were screened and any individual with diabetes, metabolic or other endocrine disorders or psychiatric illness were excluded from the study. Subjects were within 10% of their ideal body weight and drug-free for at least 1 month prior to the test. There was no history of psychiatric illness, especially depression, in their first-degree relatives. Group I ("Young"): Seven male college students ranging in age from 18 to 28 yr (21 ± 1; X ± SEM). Group II ("Older"): Nine males ranging in age from 36 to 58 yr (44 ± 2). All subjects were paid and informed consents were obtained. Following an overnight fast, an indwelling catheter was inserted into the antecubital vein and kept open with heparin-saline. Blood samples were obtained at 20-min intervals. Three base line samples were obtained before the administration of APO (0.75 mg SC), and samples were then collected over the next 140 min. The blood was then centrifuged and the serum stored at 20 C until assayed. GH concentration in the plasma was measured by a double antibody radioimmunoassay procedure utilizing 125I-HGH (New England Nuclear). Statistical evaluations were by Student's t test (13).
Results The younger subjects had a significantly greater peak GH response to APO as compared with the older subjects (Table 1). Peak responses occurred 40 to 60 min after drug administration. This difference in response between the two subject populations was not due to any difference in the mean weights of the two groups. The mean weight of the younger subjects was 169 ± 10 lb (X ± SEM), whereas the older subjects had a mean weight of 170 ± 9 lb. 162
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 21 November 2015. at 11:11 For personal use only. No other uses without permission. . All rights reserved.
163
COMMENTS TABLE 1. Growth hormone response to apomorphine administration 'lasma growth hormone (ng/ml) +20
+40
+60
+80
+ 100
+ 120
+ 140
1.5 ± 0.2
2.4 ± 0.8
19.0 ± 3.7
19.7 ± 2.4
12.9 ± 3.1
7.2 ± 2.4
3.7 ± 1.2
2.4 ± 0.6
1.0 ± 0.04
1.0 ± 0.1
3.3 ± 0.8
9.0 ±1.4
10.8 ±1.0
7.3 ± 1 . 1
2.9 + 0.7
1.5 ± 0.2
1.3 ± 0.1
NS
NS
NS
