Jvirrnul ofNcwrochunlirlry Vol. 33. pp. 973 lo 975 P~rgaamonPress Ltd 1979. Printed i n Greet Britain 0 International Society for Neurochenlistry Ltd
SHORT COMMUNICATION The effect of vasopressin on the activity of ornithine decarboxylase in rat brain and liver (Receioed 26 February 1979. Accepted 9 April 1979)
CONSIDERABLE information is available regarding stimulation of the activity of the enzyme ornithine decarboxylase (t-ornithine carboxy-lyase, EC 4.1.1.17; ODC), the ratelimiting enzyme in the biosynthesis of polyamines (RusSELL, 1973; TABOR& TABOR,1976). The induction of this enzyme has been shown to be an early event in growth and differentiation of a wide variety of cells, and is effected by many polypeptide and steroid hormones acting on their respective target tissues. Recent studies from our laboratory have shown that intraventricular administration of nerve growth factor (NGF) induces ornithine decarboxylase in rat brain and also in peripheral tissues (LEWISet a/., 1978; NAGAIAH et a/., 1978). The induction of this enzyme in peripheral tissues by intraventricular nerve growth factor can be decreased or abolished by ablation of either the pituitary or the adrenal. These data suggested that intraventricularly administered nerve growth factor acts to induce ornithine decarboxylase in peripheral tissues through the release of a pituitary hormone or hormones. Indeed, at least one pituitary peptide, growth hormone, is known to induce this enzyme in liver (RUSSELLet a/., 1970). and ACTH could also do so by causing the release of cortical steroids, known to be inducers of liver ODC & KENNEY, 1971). (PANKO In order to understand the mechanism of these inductions, we have studied the effects of various pituitary peptides on brain and liver ornithine decarboxylase. During these studies we have found that vasopressin produces a marked increase in the activity of ornithine decarboxylase. Since this appeared to be the first observation of an effect of vasopressin on ornithine decarboxylase in these tissues we have studied the details of its action.
Nerve growth factor (2.5s) was purified from the submaxillary glands of mature male mice by the procedure of BOCCHINI& ANGELETTI (1969). ~-[l-'~C]Ornithine monohydrochloride (spec. act. 60 mCi/mmol) was purchased from Amersham Corporation, Arlington Heights, IL. Liquifluor and hyamine hydroxide were obtained from New England Nuclear Corp., Boston, MA. Bovine growth hormone (1 U.S.P. unit/mg), (Lyss)-vasopressin (75 i.u./mg). and dithiothreitol were purchased from Calbiochem, La Jolla, CA. Neurotensin, oxytocin, angiotensin I1 and dexamethasone were obtained from Sigma Chemical Co.. St. Louis, MO. Enkephalinamide and substance P were purchased from Boehringer Mannheim Biochemicals, Indianapolis, IN. Center wells and rubber stoppers for the ornithine decarboxylase assay were from Kontes Glass Co., Vineland, NJ. RESULTS Intraventricular administration of vasopressin produces an increase in ornithine decarboxylase activity in brain and liver 4.5 h later (Table 1). Administration of angiotensin I1 is almost as effective, but a number of other peptides, notably oxytocin, which has a structure similar to that of vasopressin, have little or no effect on ODC. By comparison, nerve growth factor is clearly the most effective of these agents, increasing ODC activity in brain twice as much as either vasopressin or angiotensin 11. TABLE1. EFFECT OF INTRAVENTRICULAR
ADMINISTRATION OF VASOPRESSIN AND OTHER PEPTIDES ON THE ACTIVITY OF ORNITHINE DECARBOXYLASE IN BRAIN AND LIVER
Ornithine decarboxylase activity Brain Liver (nmol/h per g tissue)
Treatment
MATERIALS AND METHODS
* *
Male rats (15CL200 g) of the Sprague-Dawley strain were Buffer 0.55 0.03 1.06 f 0.04 (3) used. Some animals were hypophysectomized and some Vasopressin 2.81 0.41 28.80 k 2.76 (10) 2.90 0.67 16.16 0.68 (4) were bilaterally adrenalectomized by Zivic-Miller Labora- Angiotensin 11 1.46 f 0.24 11.87 k 1.70(4) tories, Inc., Allison Park, PA, 1 week before use. Animals Growth hormone 1.25 0.20 3.88 & 0.63 (4) were anesthetized with ether and various agents were in- Enkephalin 1.66 k 0.26 (4) 0.99 f 0.08 jected intraventricularly as previously described (LEWISet Substance- P 0.70 0.08 0.82 k 0.24 (3) Oxytocin a/., 1978).Rats were killed 4.5 h after injection in all experi0.48 f 0.06 0.96 & 0.20 ( 3 ) Neurotensin ments except when the time course of vasopressin action Nerve growth factor 6.34 0.27 43.90 5.52 (6) was studied. The activity of ornithine decarboxylase was measured as described previously (PEGG& WILLIAMS- Five microliters of buffer (0.05M-sodium acetate, pH 5.0) ASHMAN,1968; LEWISet a/., 1978). The results are alone or containing nerve growth factor (4.4 pg), growth expressed as nmol 14C0, liberatedh per g tissue. hormone, vasopressin, angiotensin 11, enkephalin, substanceP, oxytocin or neurotensin (10 pg each) were injected intraventricularly. Rats were killed 4.5 h later. Results are exAbbreviations used: ODC, ornithine decarboxylase; pressed as mean S.E.M. The number of observations is NGF, nerve growth factor. shown in brackets.
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TABLE2. ACTIVITY OF
ORNITHINE DECARBOXYLASE IN BRAIN AND LIVER OF SURGICALLY ALTERED RATS AFTER INTRAPERITONEAL ADMINISTRATION OF VASOPRESSIN AND DEXAMETHASONE
Intact Treatment Saline Dexamethasone Vasopressin Vasopressin + dexamethasone
Brain
Liver
0.33 & 0.02 0.84 f 0.05 0.80 f 0.15
1.07 f 0.17 50.40 f 3.86 35.14 f 5.94
_.
-
Ornithine decarboxylase activity Adrenalectomized (nmol/h per g tissue) Brain Liver 0.50 f 0.09 0.74 f 0.13
-
1.07 0.15 56.62 f 1.82 -
H ypophysectomized Brain
Liver
0.32 k 0.03 0.32 0.07 0.39 k 0.03
0.83 & 0.06 14.81 f 2.46 4.83 i 2.38
0.61
0.22
51.63 f 14.33
Five hundred microliters of saline alone or containing vasopressin (100 pg) was injected intraperitoneally. Dexamethasone was dissolved in 2% alcohol and 0.5 ml was given intraperitoneally. Animals were killed 4.5 h later. Results are expressed as mean f S.E.M. At least four animals were used per group. Vasopressin is also effective when given intraperitoneally. The administration of 5 pg of vasopressin gives a maximal induction in brain, while 50 pg seems necessary to elicit a maximal response in liver. The maximal activity of ODC in liver obtained by systemic administration is similar to that produced by intraventricular injection, but brain ODC activity is about one-fourth of that seen after intraventricular administration. When 100 pg of vasopressin were given intraperitoneally a stimulation of ODC activity was observed within 3 h in both brain and liver. Since previous experiments have shown that cortical 1971), steroids can induce liver ODC (PANKO& KENNEY, are synergistic in the induction of liver ODC by growth et al., 1971), and are permissive in the hormone (RICHMAN induction of brain ODC by nerve growth factor (IKENO et a!., 1978), and since vasopressin is known to release ACTH (YASUDAef a/., 1978). it seemed reasonable to investigate the influence of cortical steroids on vasopressin action (Table 2). The administration of dexamethasone alone resulted in some induction of brain and liver ODC in intact and in adrenalectomized animals. Hypophysectomized animals, on the other hand, do not exhibit full induction of either brain or liver ODC with dexamethasone. This finding suggests that a pituitary factor (or factors) is also involved in the induction. That vasopressin might be such a factor is suggested by the observation that the combination of dexamethasone and vasopressin produces as much increase in ODC activity in the brains and livers of hypophysectomized animals as does dexamethasone alone in intact animals. Indeed, the effect of the combination of vasopressin and dexamethasone in the livers of these animals more than the additive effect of vasopressin and dexamethasone alone. DISCUSSION The mechanism by which intraventricularly administered nerve growth factor stimulates the activity of ornithine decarboxylase in brain and in peripheral tissues is ef a/., 1978)sugunknown. Ablation experiments (NAGAIAH gested that the induction, in peripheral tissues at least, is caused by the release of pituitary factors. Consistent with this suggestion is the finding that intraventricular injection of NGF causes a substantial increase in plasma corticoet al., 1978). Since this sterone levels within 1 h NAGAIAH increase is probably produced by a release of ACTH, and since several other peptides, when injected intraventricularly. cause ACTH release, it seemed reasonable to ask if any of these mimic N G F action on ODC. Vasopressin
is one such peptide (YASUDA et al., 1978); the present work shows that vasopressin does mimic N G F action in inducing ODC in brain and liver. This appears to be the first report of the action of a posterior pituitary peptide on ornithine decarboxylase in these tissues. At the doses tested, vasopressin and angiotensin I1 were comparable in their ability to stimulate ODC activity in adult rat brain. Since one of the roles of angiotensin I1 is to release vasopressin (Mouw et ul., 1971), intraventricular angiotensin I1 may cause the elevation and release of vasopressin which, in turn, stimulates hepatic ODC. Although vasopressin can mimic NGF, the specificity of the ODC induction is still remarkable. Growth hormone is somewhat effective, as has also been reported by others (ROGERer d.,1974), but a number of peptides are without effect, among them oxytocin, which is structurally related to vasopressin. Also without substantial effect were enkephalin, substance P and neurotensin. Previous studies have shown that glucagon, insulin, cytochrome c, and bovine et al.. 1978). serum albumin were also ineffective (NAGAIAH Vasopressin was also active when injected intraperitoneally and increased the activity of hepatic, and also of brain, ODC within a few hours. The time course of the increase in the two tissues appeared to be different in that maximal stimulation in liver occurred within 4-5 h after administration, whereas the maximal enhancement of brain ODC occurred somewhat later; this is comparable to previous observations made after intraventricular administraet al., 1978). Another tion of nerve growth factor (NAGAIAH difference between the tissues is that 10 pg of vasopressin injected intraperitoneally caused full induction of ODC in brain, but no induction in liver. Thus. the different time course of induction in the two organs and the difference in the dose-response curves suggest that there is some difference in the details of the induction in brain and liver. It should be clearly stated that the stimulation of brain and liver ODC levels by vasopressin could be. or is even likely to be, secondary to its effect on the levels of other hormones. One possible mechanism which can be considered is the following. Vasopressin given intravenously has been found to act directly on the anterior pituitary, et a/., 1978). Under certain causing ACTH release (YASUDA conditions vasopressin can also affect the release of growth hormone (MARTINet al., 1978). Since the vasopressininduced stimulation of hepatic ODC is abolished by hypophysectomy, and since dexamethasone does not elevate hepatic ODC fully in hypophysectomized animals, but the combination of vasopressin and dexamethasone does, it seems possible that pituitary factor(s) released by vasopres-
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mone regulation, in The Hypothalamus (REICHLIN S.. BALDESSARINI R. J. & MARTINJ. B., eds.), pp. 329--357. Raven Press, New York. Mouw D., BONJOUR J.-P., MALVINR. L. & VANDER A. (1971) Central action of angiotensin in stimulating ADH release. Am. J . Physiol. 220, 239-242. NAGAIAH K., IKENOT., LAKSHMANAN J., MACDONNELL P. & GUROFFG. (1978) Intraventricular administration of nerve growth factor induces ornithine decarboxylase in peripheral tissues of the rat. Proc. natn. Acad. Sci., U S A . 75, 2512-2515. PANKOW. B. & KENNEYF. T. (1971) Hormonal stimuSection on Intermediary Metabolism, TAKEYUKI IKENO lation of hepatic ornithine decarboxylase. Biochern. hioLaboratory of Deoelopmental GORDONGUROFF phys. Res. Commun. 43, 346-350. N eurob iology, PEGGA. E. & WILLIAMS-ASHMAN H. G. (1968) Biosynthesis National Institute of Child Health and of putrescine in the prostate gland of the rat. Biocheni. Human Detrelopmnent, J . 108, 533-539. National Institirtes of Health, RICHMANR. A,, UNDERWOOD L. E., VAN WYK J. J. & Bethesda, M D 20205, U.S.A. VOINAS. J. (1971) Synergistic effect of cortisol and growth hormone on hepatic ornithine decarboxylase activity. Proc. Soc. exp. Biol. Med. 138, 88@884. REFERENCES ROGER L. J., SCHANBERG S. M. & FELLOWS R. E. (1974) Growth and lactogenic hormone stimulation of ornithBOCCHINIV. & ANGELETTI P. U. (1969) The nerve growth ine decarboxylase in neonatal rat brain. Endocrinology factor: purification of a 30,000 molecular weight protein. 95, 904911. Proc. natn. Acad. Sci., U.S.A. 64, 787-794. D. H.. ed. (1973) Polyamines in Normal and NeoIKENOT., MACDONNELL P. C., NAGAIAH K. & GUROFF RUSSELL plastic Growth. Raven Press, New York. G. (1978) The permissive effect of cortical steroids on the induction of brain ornithine decarboxylase by nerve RUSSELLD. H., SNYDERS. H. & MEDINAV. J. (1970) Growth hormone induction of ornithine decarboxylase growth factor. Biochem. biophys. Res. Commun. 82, in rat liver. Endocrinology 86, 1414-1419. 957-963. LEWISM. E., LAKSHMANAN J., NAGAIAH K., MACDONNELLTABORC. W. & TABOR H. (1976) 1,4-Diaminobutane (putrescine), spermidine, and spermine. A . Reu. Biochem. P. C. & GUROFF G. (1978) Nerve growth factor increases 45, 285-306. activity of ornithine decarboxylase in rat brain. Proc. YASUDAN., GREERM. A., GREERS. E. & PANTON P. (1978) natn. Acad. Sci.. U.S.A. 75, 1021-1023. Studies on the site of action of vasopressin in inducing MARTINJ. B., BRAZEAUP., TANNENBAUM G. S., WILLOUGHBY J. o., EPELRAUM J., TERRYL. c. & DURAND adrenocorticotropin secretion. Endocrinology 103, D. (1978) Neuroendocrine organization of growth hor906-91 1.
sin or by the combination of dexamethasone and vasopressin cause the full induction of hepatic ODC. One of these factors may be ACTH, which may act directly on the liver and the brain, and independently of its role in corticosteroid release. Another might be growth hormone, because when it is administered intraventricularly it also has some effect in inducing liver ODC. In any case, it seems possible that the intraventricular administration of peptides such as nerve growth factor and vasopressin act on tissue ODC levels by an activation of the hypothalamus and/or the pituitary.
SHORT COMMUNICATION The effect of vasopressin on the activity of ornithine decarboxylase in rat brain and liver (Receioed 26 February 1979. Accepted 9 April 1979)
CONSIDERABLE information is available regarding stimulation of the activity of the enzyme ornithine decarboxylase (t-ornithine carboxy-lyase, EC 4.1.1.17; ODC), the ratelimiting enzyme in the biosynthesis of polyamines (RusSELL, 1973; TABOR& TABOR,1976). The induction of this enzyme has been shown to be an early event in growth and differentiation of a wide variety of cells, and is effected by many polypeptide and steroid hormones acting on their respective target tissues. Recent studies from our laboratory have shown that intraventricular administration of nerve growth factor (NGF) induces ornithine decarboxylase in rat brain and also in peripheral tissues (LEWISet a/., 1978; NAGAIAH et a/., 1978). The induction of this enzyme in peripheral tissues by intraventricular nerve growth factor can be decreased or abolished by ablation of either the pituitary or the adrenal. These data suggested that intraventricularly administered nerve growth factor acts to induce ornithine decarboxylase in peripheral tissues through the release of a pituitary hormone or hormones. Indeed, at least one pituitary peptide, growth hormone, is known to induce this enzyme in liver (RUSSELLet a/., 1970). and ACTH could also do so by causing the release of cortical steroids, known to be inducers of liver ODC & KENNEY, 1971). (PANKO In order to understand the mechanism of these inductions, we have studied the effects of various pituitary peptides on brain and liver ornithine decarboxylase. During these studies we have found that vasopressin produces a marked increase in the activity of ornithine decarboxylase. Since this appeared to be the first observation of an effect of vasopressin on ornithine decarboxylase in these tissues we have studied the details of its action.
Nerve growth factor (2.5s) was purified from the submaxillary glands of mature male mice by the procedure of BOCCHINI& ANGELETTI (1969). ~-[l-'~C]Ornithine monohydrochloride (spec. act. 60 mCi/mmol) was purchased from Amersham Corporation, Arlington Heights, IL. Liquifluor and hyamine hydroxide were obtained from New England Nuclear Corp., Boston, MA. Bovine growth hormone (1 U.S.P. unit/mg), (Lyss)-vasopressin (75 i.u./mg). and dithiothreitol were purchased from Calbiochem, La Jolla, CA. Neurotensin, oxytocin, angiotensin I1 and dexamethasone were obtained from Sigma Chemical Co.. St. Louis, MO. Enkephalinamide and substance P were purchased from Boehringer Mannheim Biochemicals, Indianapolis, IN. Center wells and rubber stoppers for the ornithine decarboxylase assay were from Kontes Glass Co., Vineland, NJ. RESULTS Intraventricular administration of vasopressin produces an increase in ornithine decarboxylase activity in brain and liver 4.5 h later (Table 1). Administration of angiotensin I1 is almost as effective, but a number of other peptides, notably oxytocin, which has a structure similar to that of vasopressin, have little or no effect on ODC. By comparison, nerve growth factor is clearly the most effective of these agents, increasing ODC activity in brain twice as much as either vasopressin or angiotensin 11. TABLE1. EFFECT OF INTRAVENTRICULAR
ADMINISTRATION OF VASOPRESSIN AND OTHER PEPTIDES ON THE ACTIVITY OF ORNITHINE DECARBOXYLASE IN BRAIN AND LIVER
Ornithine decarboxylase activity Brain Liver (nmol/h per g tissue)
Treatment
MATERIALS AND METHODS
* *
Male rats (15CL200 g) of the Sprague-Dawley strain were Buffer 0.55 0.03 1.06 f 0.04 (3) used. Some animals were hypophysectomized and some Vasopressin 2.81 0.41 28.80 k 2.76 (10) 2.90 0.67 16.16 0.68 (4) were bilaterally adrenalectomized by Zivic-Miller Labora- Angiotensin 11 1.46 f 0.24 11.87 k 1.70(4) tories, Inc., Allison Park, PA, 1 week before use. Animals Growth hormone 1.25 0.20 3.88 & 0.63 (4) were anesthetized with ether and various agents were in- Enkephalin 1.66 k 0.26 (4) 0.99 f 0.08 jected intraventricularly as previously described (LEWISet Substance- P 0.70 0.08 0.82 k 0.24 (3) Oxytocin a/., 1978).Rats were killed 4.5 h after injection in all experi0.48 f 0.06 0.96 & 0.20 ( 3 ) Neurotensin ments except when the time course of vasopressin action Nerve growth factor 6.34 0.27 43.90 5.52 (6) was studied. The activity of ornithine decarboxylase was measured as described previously (PEGG& WILLIAMS- Five microliters of buffer (0.05M-sodium acetate, pH 5.0) ASHMAN,1968; LEWISet a/., 1978). The results are alone or containing nerve growth factor (4.4 pg), growth expressed as nmol 14C0, liberatedh per g tissue. hormone, vasopressin, angiotensin 11, enkephalin, substanceP, oxytocin or neurotensin (10 pg each) were injected intraventricularly. Rats were killed 4.5 h later. Results are exAbbreviations used: ODC, ornithine decarboxylase; pressed as mean S.E.M. The number of observations is NGF, nerve growth factor. shown in brackets.
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974
Short communication
TABLE2. ACTIVITY OF
ORNITHINE DECARBOXYLASE IN BRAIN AND LIVER OF SURGICALLY ALTERED RATS AFTER INTRAPERITONEAL ADMINISTRATION OF VASOPRESSIN AND DEXAMETHASONE
Intact Treatment Saline Dexamethasone Vasopressin Vasopressin + dexamethasone
Brain
Liver
0.33 & 0.02 0.84 f 0.05 0.80 f 0.15
1.07 f 0.17 50.40 f 3.86 35.14 f 5.94
_.
-
Ornithine decarboxylase activity Adrenalectomized (nmol/h per g tissue) Brain Liver 0.50 f 0.09 0.74 f 0.13
-
1.07 0.15 56.62 f 1.82 -
H ypophysectomized Brain
Liver
0.32 k 0.03 0.32 0.07 0.39 k 0.03
0.83 & 0.06 14.81 f 2.46 4.83 i 2.38
0.61
0.22
51.63 f 14.33
Five hundred microliters of saline alone or containing vasopressin (100 pg) was injected intraperitoneally. Dexamethasone was dissolved in 2% alcohol and 0.5 ml was given intraperitoneally. Animals were killed 4.5 h later. Results are expressed as mean f S.E.M. At least four animals were used per group. Vasopressin is also effective when given intraperitoneally. The administration of 5 pg of vasopressin gives a maximal induction in brain, while 50 pg seems necessary to elicit a maximal response in liver. The maximal activity of ODC in liver obtained by systemic administration is similar to that produced by intraventricular injection, but brain ODC activity is about one-fourth of that seen after intraventricular administration. When 100 pg of vasopressin were given intraperitoneally a stimulation of ODC activity was observed within 3 h in both brain and liver. Since previous experiments have shown that cortical 1971), steroids can induce liver ODC (PANKO& KENNEY, are synergistic in the induction of liver ODC by growth et al., 1971), and are permissive in the hormone (RICHMAN induction of brain ODC by nerve growth factor (IKENO et a!., 1978), and since vasopressin is known to release ACTH (YASUDAef a/., 1978). it seemed reasonable to investigate the influence of cortical steroids on vasopressin action (Table 2). The administration of dexamethasone alone resulted in some induction of brain and liver ODC in intact and in adrenalectomized animals. Hypophysectomized animals, on the other hand, do not exhibit full induction of either brain or liver ODC with dexamethasone. This finding suggests that a pituitary factor (or factors) is also involved in the induction. That vasopressin might be such a factor is suggested by the observation that the combination of dexamethasone and vasopressin produces as much increase in ODC activity in the brains and livers of hypophysectomized animals as does dexamethasone alone in intact animals. Indeed, the effect of the combination of vasopressin and dexamethasone in the livers of these animals more than the additive effect of vasopressin and dexamethasone alone. DISCUSSION The mechanism by which intraventricularly administered nerve growth factor stimulates the activity of ornithine decarboxylase in brain and in peripheral tissues is ef a/., 1978)sugunknown. Ablation experiments (NAGAIAH gested that the induction, in peripheral tissues at least, is caused by the release of pituitary factors. Consistent with this suggestion is the finding that intraventricular injection of NGF causes a substantial increase in plasma corticoet al., 1978). Since this sterone levels within 1 h NAGAIAH increase is probably produced by a release of ACTH, and since several other peptides, when injected intraventricularly. cause ACTH release, it seemed reasonable to ask if any of these mimic N G F action on ODC. Vasopressin
is one such peptide (YASUDA et al., 1978); the present work shows that vasopressin does mimic N G F action in inducing ODC in brain and liver. This appears to be the first report of the action of a posterior pituitary peptide on ornithine decarboxylase in these tissues. At the doses tested, vasopressin and angiotensin I1 were comparable in their ability to stimulate ODC activity in adult rat brain. Since one of the roles of angiotensin I1 is to release vasopressin (Mouw et ul., 1971), intraventricular angiotensin I1 may cause the elevation and release of vasopressin which, in turn, stimulates hepatic ODC. Although vasopressin can mimic NGF, the specificity of the ODC induction is still remarkable. Growth hormone is somewhat effective, as has also been reported by others (ROGERer d.,1974), but a number of peptides are without effect, among them oxytocin, which is structurally related to vasopressin. Also without substantial effect were enkephalin, substance P and neurotensin. Previous studies have shown that glucagon, insulin, cytochrome c, and bovine et al.. 1978). serum albumin were also ineffective (NAGAIAH Vasopressin was also active when injected intraperitoneally and increased the activity of hepatic, and also of brain, ODC within a few hours. The time course of the increase in the two tissues appeared to be different in that maximal stimulation in liver occurred within 4-5 h after administration, whereas the maximal enhancement of brain ODC occurred somewhat later; this is comparable to previous observations made after intraventricular administraet al., 1978). Another tion of nerve growth factor (NAGAIAH difference between the tissues is that 10 pg of vasopressin injected intraperitoneally caused full induction of ODC in brain, but no induction in liver. Thus. the different time course of induction in the two organs and the difference in the dose-response curves suggest that there is some difference in the details of the induction in brain and liver. It should be clearly stated that the stimulation of brain and liver ODC levels by vasopressin could be. or is even likely to be, secondary to its effect on the levels of other hormones. One possible mechanism which can be considered is the following. Vasopressin given intravenously has been found to act directly on the anterior pituitary, et a/., 1978). Under certain causing ACTH release (YASUDA conditions vasopressin can also affect the release of growth hormone (MARTINet al., 1978). Since the vasopressininduced stimulation of hepatic ODC is abolished by hypophysectomy, and since dexamethasone does not elevate hepatic ODC fully in hypophysectomized animals, but the combination of vasopressin and dexamethasone does, it seems possible that pituitary factor(s) released by vasopres-
Short communication
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mone regulation, in The Hypothalamus (REICHLIN S.. BALDESSARINI R. J. & MARTINJ. B., eds.), pp. 329--357. Raven Press, New York. Mouw D., BONJOUR J.-P., MALVINR. L. & VANDER A. (1971) Central action of angiotensin in stimulating ADH release. Am. J . Physiol. 220, 239-242. NAGAIAH K., IKENOT., LAKSHMANAN J., MACDONNELL P. & GUROFFG. (1978) Intraventricular administration of nerve growth factor induces ornithine decarboxylase in peripheral tissues of the rat. Proc. natn. Acad. Sci., U S A . 75, 2512-2515. PANKOW. B. & KENNEYF. T. (1971) Hormonal stimuSection on Intermediary Metabolism, TAKEYUKI IKENO lation of hepatic ornithine decarboxylase. Biochern. hioLaboratory of Deoelopmental GORDONGUROFF phys. Res. Commun. 43, 346-350. N eurob iology, PEGGA. E. & WILLIAMS-ASHMAN H. G. (1968) Biosynthesis National Institute of Child Health and of putrescine in the prostate gland of the rat. Biocheni. Human Detrelopmnent, J . 108, 533-539. National Institirtes of Health, RICHMANR. A,, UNDERWOOD L. E., VAN WYK J. J. & Bethesda, M D 20205, U.S.A. VOINAS. J. (1971) Synergistic effect of cortisol and growth hormone on hepatic ornithine decarboxylase activity. Proc. Soc. exp. Biol. Med. 138, 88@884. REFERENCES ROGER L. J., SCHANBERG S. M. & FELLOWS R. E. (1974) Growth and lactogenic hormone stimulation of ornithBOCCHINIV. & ANGELETTI P. U. (1969) The nerve growth ine decarboxylase in neonatal rat brain. Endocrinology factor: purification of a 30,000 molecular weight protein. 95, 904911. Proc. natn. Acad. Sci., U.S.A. 64, 787-794. D. H.. ed. (1973) Polyamines in Normal and NeoIKENOT., MACDONNELL P. C., NAGAIAH K. & GUROFF RUSSELL plastic Growth. Raven Press, New York. G. (1978) The permissive effect of cortical steroids on the induction of brain ornithine decarboxylase by nerve RUSSELLD. H., SNYDERS. H. & MEDINAV. J. (1970) Growth hormone induction of ornithine decarboxylase growth factor. Biochem. biophys. Res. Commun. 82, in rat liver. Endocrinology 86, 1414-1419. 957-963. LEWISM. E., LAKSHMANAN J., NAGAIAH K., MACDONNELLTABORC. W. & TABOR H. (1976) 1,4-Diaminobutane (putrescine), spermidine, and spermine. A . Reu. Biochem. P. C. & GUROFF G. (1978) Nerve growth factor increases 45, 285-306. activity of ornithine decarboxylase in rat brain. Proc. YASUDAN., GREERM. A., GREERS. E. & PANTON P. (1978) natn. Acad. Sci.. U.S.A. 75, 1021-1023. Studies on the site of action of vasopressin in inducing MARTINJ. B., BRAZEAUP., TANNENBAUM G. S., WILLOUGHBY J. o., EPELRAUM J., TERRYL. c. & DURAND adrenocorticotropin secretion. Endocrinology 103, D. (1978) Neuroendocrine organization of growth hor906-91 1.
sin or by the combination of dexamethasone and vasopressin cause the full induction of hepatic ODC. One of these factors may be ACTH, which may act directly on the liver and the brain, and independently of its role in corticosteroid release. Another might be growth hormone, because when it is administered intraventricularly it also has some effect in inducing liver ODC. In any case, it seems possible that the intraventricular administration of peptides such as nerve growth factor and vasopressin act on tissue ODC levels by an activation of the hypothalamus and/or the pituitary.
