Prolactin selectively stimulates ornithine decarboxylase in the lateral lobe of the rat prostate

89

Molecular and Cellular Endocrinology, 50 (1987) 89-97 Elsevier Scientific Publishers Ireland, Ltd.

MCE 01610

Prolactin selectively stimulates ornithine decarboxylase in the lateral lobe of the rat prostate H. Rui and K. Purvis Institute of Pathology, The National Hospital, Oslo, Norway (Received

Key WO~G!KProlactin;

Prostate;

(Lateral

11 August

lobe); Omithine

1986; accepted

decarboxylase;

31 October

Polyamines:

1986)

(Rat)

In androgenized-hypophysectornized rats, ovine prolactin stimulated the activity of the ornithine decarboxylase (ODC) of the lateral lobes, but not the ventral and dorsal lobes of the prostate glands in a time- and dose-dependent fashion. High degrees of enzyme stimulation were associated with significant elevations in the endogenous levels of its product, putrescine. The relative response to prolactin over basal activities was relatively unaffected by indomethacin but decreased with cycloheximide, suggesting that prostaglandins do not mediate the effects of the hormone, but that a high rate of protein synthesis is a prerequisite for its expression. Indomethacin alone significantly increased the basal activity of the enzyme above control levels, suggesting that prostaglandins may normally exert a degree of inhibition on the ODC. The selective activation of the lateral lobe ODC supports previous reports of a differential response of the various prostatic lobes to prolactin, and also provides a convenient biochemical response for examining details of prolactin action on this organ.

Introduction Evidence has accumulated that prolactin has a regulatory function in male reproductive physiology, and an increasing number of articles indicate that it is involved in the control of prostatic function (Bartke, 1980; Horrobin, 1980; Rui et al., 1985). Most of the work has been carried out on non-human species, although effects also have been reported on human prostatic cells (Syms et al., 1985). In other organ systems evidence has been presented that prolactin may exert at least some of its effects by stimulating the endogenous levels of

Address for correspondence: H. Rui, Institute thology, Rikshospitalet, 0027 Oslo 1, Norway. 0303-7207/87/$03.50

0 1987 Elsevier Scientific

of

Publishers

Pa-

Ireland,

polyamines (Oka and Perry, 1976; Rillema, 1976; Manni and Wright, 1985), which are believed to constitute general mediators of RNA and protein synthesis in somatic cells (Russell, 1980). The intention of the present study was therefore to test whether the same hormone could activate this pathway in the rat prostate. In particular, the study focusses on the capacity for prolactin to activate the rate limiting enzyme in the polyamine biosynthetic pathway, omithine decarboxylase (ODC). Since the various lobes of the prostate appear to exhibit differential sensitivities in their response to prolactin, at least with regard to organ weight and citric acid production (Grayhack, 1963; Slaunwhite and Sharma, 1977; Prins and Lee, 1983), each study involved a comparison of the effects of prolactin on all three lobes of the prosLtd.

90

tatic complex. Moreover, enzyme and polyamine analyses were also carried out on kidney tissue isolated from the same animals as a control. All studies were carried out on androgen-treated, hypophysectomized rats to exclude the confounding effects of other hormones. Materials and methods Time-response study Male Sprague-Dawley rats (250 g) were hypophysectomized at 60 days of age (Merllegaard Breeding Centre, Denmark), and injected from day 67 daily with 500 pg testosterone oenanthate (TO) in 0.1 ml peanut oil i.m. for 28 days. Animals were then randomly divided into groups of five, and given 1 mg ovine PRL (31 IU/mg; Sigma Chem. Co., U.S.A.) in 1 ml phosphate-buffered saline (PBS) S.C. A control group of five rats was sacrificed at the time of injection. The prolactininjected animals were sacrificed after 6, 12,18 and 24 h. The animals were killed by cervical dislocation under ether anaesthesia, and ventral (VL), lateral (LL) and dorsal lobes (DL) of the prostate were removed according to Gerhardt et al. (1983) and frozen immediately in a solid CO,-ethanol bath. Kidney tissue was also removed from the same animals. All tissues were stored at - 70” C and assayed for ODC activity within 3 days. Dose-response study Male Sprague-Dawley rats were hypophysectomized at 60 days, and androgen substitution (500 pg TO in peanut oil) was initiated after 7 days. After 14 days of steroid treatment four groups of five animals were exposed to a single S.C. injection of prolactin in the following doses: 50, 200, 600 and 1000 pg in 1 ml of PBS. A control group received PBS only. The animals were then killed after 12 h, a time which had been shown in the first study to correspond to a maximum response. Effects of indomethacin and cycloheximide on the prolactin-induced ODC response Male Sprague-Dawley rats were hypophysectomized and androgen-substituted as above. After 21 days of steroid treatment six groups of five animals were exposed to the following regimen: Three groups received 1 mg prolactin (s.c.), two of

these had been treated with a single injection (i.p.) of indomethacin (1 mg in 1 ml PBS, 4 mg/kg; Confortid, Dumex, Denmark) or cycloheximide (500 pg in 1 ml PBS, 2 mg/kg; Sigma Chem. Co., U.S.A.) 2 h earlier. The dose of indomethacin used was the same as that found to alter membrane fluidity in the rat prostate by Dave and Witorsch (1983). The decision to use the above dose of cycloheximide was based on the studies by Rothblum et al. (1976) in rat liver. Three control groups received PBS vehicle, indomethacin or cycloheximide. All animals were sacrificed 8 h after prolactin injection. Assay of ODC The assay is based on the measurement of 14C0, liberated from “C-ornithine and was originally published by Kobayashi et al. (1971). The details of our own application of the technique to prostatic tissue have been described elsewhere (Rui et al., 1986). Briefly, tissues were homogenized on ice for 45 s in 20 ~01s. of Tris-HCl buffer (50 mM, pH 7.2), containing 5 mM dithiothreitol (DTT), 0.1 mM EDTA and 0.2 mM pyridoxal phosphate (Sigma Chem. Co., U.S.A.), followed by the centrifugation at 20 000 X g for 30 min. An aliquot (100 ~1) was taken for polyamine determinations, and 1 ml was transferred to 25 ml flasks and used in the enzyme assay. The reaction was started by the addition of 1 ml buffer containing 200 nmol of L-ornithine and 2 nmol of “C-(Dr_)-ornithine (61 ~Ci/mmol; Amersham, U.K.) in the cases of ventral lobe and dorsal lobe cytosols, and 50 nmol and 4 nmol, respectively, when the lateral lobe and kidney cytosols were examined. The flasks were closed with rubber stoppers, and incubated in a shaking water bath at 37°C for 30 min. The reaction was terminated by injecting 1 ml 2 M citric acid through the rubber stopper. It was allowed to stand for a further 60 min to ensure the complete release of CO,, which was absorbed by a Whatman 17 filter strip containing 50 ~1 of ethanolamine (Sigma Chemical Co.) diluted to 33% in ethylene glycol. The filter strip was placed in a plastic well held by the rubber stopper. After incubation, the paper was transferred to vials containing 10 ml scintillation fluid (Hydroluma, Lumac Systems, U.S.A.), and counted. The protein concentrations and the incubation times used

91

in the assay were derived from the linear portion of the activity curves which were linear between 0.5 and 5 mg protein, and 0 and 40 min of incubation (data not shown). Assay of polyamines The method is based on the fluorescent detection of dansylated amine derivatives after HPLC separation and has been described in detail elsewhere (Rui et al., 1985). Two steps in the procedure have been modified: 10% trichloroacetic acid (TCA) was used to deproteinize the samples instead of 0.4 M perchloric acid. The TCA was then removed by extraction twice with 2.5 ~01s. of diethyl ether. Instead of 0.11 M dansyl chloride, 0.011 M was used, which was found to reduce the background fluorescence without affecting the linearity of the standard curve. Different aliquots were taken from supernatants prepared for ODC analysis for the ventral lobe and dorsal lobe assays (100 ~1) and the lateral lobe and kidney polyamine measurements (400 ~1). Protein determination Protein was determined et al. (1951).

by the method of Lowry

Statistical analysis Differences between the various groups were tested by one-way analysis of variance. The data was logarithmically transformed prior to analysis to normalize the variances of the different groups. Results Time-response study A single prolactin injection in androgenized-hypophysectomized rats stimulated ODC lo-fold in the lateral lobe of the prostate, a response which was comparable to that observed in the kidney (15-fold; Fig. 1). Prolactin did not influence the activity of the enzyme in the ventral or dorsal lobes of the prostate. The enzyme was maximally activated between 6 and 18 h in the lateral lobe and kidney, but by 24 h the activity had begun to fall towards control levels. The tissue concentrations (expressed per mg protein) of putrescine and the polyamines in prostatic tissues and kidney after this prolactin treatment are summarized in Table 1. In both the lateral lobe and l&hey,

putrescine levels were elevated 2-fold (P < 0.05) after 6 h, but showed no further increase during the 24 h observation period. Spermidine concentrations underwent a doubling (P < 0.05) in lateral lobe during the first 12 h, whereas the same amine in the kidney tissue exhibited a time-dependent decrease (P < 0.05). The spermine levels remained unaffected throughout the observation period in both these tissues. In the dorsal and ventral lobes, in which no ODC response to prolactin was recorded, no alterations were observed in the levels of putrescine. However, in the latter lobe, spermidine and spermine underwent a gradual, time-dependent decrease to 63 and 44% (P < 0.01) of control levels at 24 h, respectively. Neither of these polyamines was affected by prolactin in the dorsal lobe. Table 2 summarizes the ventral and lateral lobe weights and protein concentrations in the time-response study. In the case of the dorsal lobe and kidney, only portions of the organs were removed and therefore total organ weights could not be obtained. Lateral lobe weights were already significantly stimulated (P < 0.05) 6 h after hormone injection, and increased further thereafter. Ventral lobe weights, in contrast, were unaffected. No significant alterations in the protein concentrations in either lobe could be recorded over the same observation period. Dose-response study Single injections of increasing doses of prolactin in androgenized-hypophysectomized rats resulted in an activation of the ODC after 12 h, a result which confirmed the findings of the time-response study (Fig. 2). The maximum response elicited in this study was equivalent to a 2- to 3-fold stimulation of the lateral lobe ODC (P < 0.01) and a lo-fold stimulation of the kidney ODC (P < 0.001). This response was obtained with 200-1000 pg of prolactin in both organs. Ventral lobe and dorsal lobe ODC did not respond to any of the doses tested (data not shown). In this study no significant alterations in polyamine levels, except for a 2-fold stimulation of kidney putrescine (P < 0.05), were observed (data not shown). Effects of indomethacin and cycloheximide on the prolactin-induced ODC response (Table 3) Prolactin in the control animals evoked a 2- to

12-

h .; $

DL

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: 864.

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8

: 0 E

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0

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12 Time

I

I

18

24

o s

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L

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6

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12 Time

(h)

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1

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(h)

Kidney ;:

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(h)

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Fig. 1. Time-related alterations in ornithine decarboxylase (ODC) activation in the ventral (VL), lateral (LL) and dorsal (DL) lobes and kidneys of androgenized-hypophysectomized rats (five animals per group) after a single S.C. injection of ovine prolactin (1 mg). Values represent geometric means and vertical bars are 95% confidence limits.

3-fold stimulation of the lateral lobe ODC (P -Z 0.01) and a 8- to 9-fold increase in the kidney ODC (P < 0.001) 8 h after injection (Table 3). Indomethacin alone led to an approximate doubling of the basal ODC activity in both organs (P < 0.05), although in the same tissues the relative response to prolactin was not altered. In contrast, indomethacin had no effect on the enzyme in the ventral lobe. There were no significant alterations in the concentrations of putrescine or

polyamines induced by prolactin, indomethacin or a combination of the two in any of the tissues examined. Cycloheximide stimulated the basal activity of the ODC in both the lateral lobe (3-fold; P < 0.001) and kidney (2- to 3-fold; P -c0.05) and reduced or abolished the relative prolactin-stimulated response in these organs, respectively. In contrast, the basal enzyme activity in the ventral lobe was significantly reduced (P < 0.001). This

93

TABLE 1 EFFECTS OF A SINGLE INJECTION OF OVINE PROLACTIN (1 mg) IN ANDROGENIZED-HYPOPHYSECTOMIZED RATS ON PUTRESCINE AND POLYAMINE CONCENTRATIONS IN VENTRAL LOBE (VL), LATERAL LOBE (LL) AND DORSAL LOBES (DL) OF THE PROSTATE AND IN THE KIDNEY Time after injection Putrescine

18 h

12 h

6h

Control

24 h

a

VL LL DL Kidney

3.5 0.56 1.7 0.060

(2.7 (0.45 (1.4 (0.021-

Spermidine VL LL DL Kidney

63 9.0 72 2.3

(49 (5.2

Spermine VL LL DL Kidney

21 7.5 49 6.3

(16 (3.8

(61 (1.8

(39 (5.0

4.5) b 0.71) 2.2) 0.13)

3.6 1.2 1.2 0.13

(2.5 (0.92(0.88(O.lO-

5.1) 1.5) 1.8) 0.16)

4.1 1.0 1.7 0.14

(3.2 (0.50(1.4 (O.ll-

5.3) 2.0) 2.2) 0.17)

3.0 1.1 2.7 0.14

(2.0 (0.75(2.1 (0.09-

4.8) 1.5) 3.6) 0.23)

2.6 (2.1 1.0 (0.69 (1.8 2.3 0.091 (0.062-

3.2) 1.5) 2.8) 0.15)

-81) -15) -85) - 2.9)

60 (50 9.9 (5.1 78 (61 1.8 (1.7

-72) -30) -99) - 1.9)

50 (41 (9.4 18 69 (45 1.9 (1.6

- 60) - 35) -104) - 2.3)

52 (31 23 (18 88 (54 1.6 (1.5

- 86) - 30) -145) 1.7)

40 24 84 1.6

(34 (18 (66 (1.5

- 46) - 31) -105) 1.8)

-28) -15) -61) - 8.1)

16 (12 8 (5.2 58 (50 4.6 (4.1

-20) -12) -68) - 5.2)

9.7 (6.1 7.7 (2.7 51 (30 5.4 (4.2

- 15) - 22) - 87) - 6.8)

11 (6.3 8 (6.3 857 (27 5.0 (4.4

- 19) - 10) -119) 5.8)

9.3 9.1 58 5.9

(7.3 (7.8

- 12) - 11) - 77) - 7.2)

(43 (4.8

a Putrescine and polyamine levels are expressed as nmol/mg protein. b Values represent geometric means and 95% confidence limits ( ).

inhibition of the enzyme was not associated with any significant alteration in the levels of the amines. On the other hand, stimulation of the basal ODC by this drug in the lateral lobe and kidney was also associated with a significant elevation in putrescine concentrations above control levels (2-fold; P -c0.05 and 4- to 5-fold, P <

0.001, respectively). Whereas the levels of the polyamines, spermidine and spermine, in kidney tissue were unaffected by cycloheximide treatment, the same drug induced a significant decrease in these amines in the lateral lobe (P < 0.05 and P c 0.01, respectively).

TABLE 2 TIME-RELATED EFFECTS OF A SINGLE INJECTION OF OVINE PROLACTIN (1 mg) ON THE WEIGHTS (mg) AND CYTOSOLIC PROTEIN CONCENTRATIONS (mg/g FRESH WEIGHT) OF THE VENTRAL LOBE (VL) AND LATERAL LOBE (LL) IN ANDROGENIZED-HYPOPHYSECTOMIZED RATS (FIVE ANIMALS PER GROUP) Control

6h

12 h

425 (398-453) = 115 (98-136)

425 (369-489) 141(117-170)

18 h

24 h

Weight

VL LL

*

452 (404-504) 185 (144-238)

**

438 (386-496) 190 (147-246)

**

465 (401-538) 169 (136-209)

Protein

VL LL

63 (5432 (25-

73) 42)

66 (5932 (26-

73) 40)

54 (5733 (24-

a Values represent geometric means and 95% confidence limits ( ). * Pi 0.05; ** P < 0.01.

73) 46)

61 (5336 (31-

69) 42)

71 (6639 (31-

76) 49)

**

7.0 10 5.6

Spermine VL LL Kidney

3.9) 0.47) 0.32)

6.0 6.3 5.7

(3.3 -11) (3.8 -11) (4.8 - 6.7)

26 (13 -50) 10 (7.1 -16) 2.1 (1.8 - 2.4)

1.9 (0.920.32 (0.220.27 (0.23-

16 (12 -22) 0.82 (0.49- 1.4) 3.5 (1.8 - 7.0)

Prolactin

8.5 12 5.9

(8.0 - 9.1) (6.5 -21) (4.7 - 7.4)

32 (29 -35) 20 (11 -36) 2.2 (1.8 - 2.8)

2.0 (1.5 - 2.5) 0.63 (0.5 - 0.78) 0.26 (0.19- 0.36)

14 (9.8 -19) 0.78 (0.46- 1.3) 0.86 (0.41- 1.8)

Indomethacin

a ODC activity is expressed as pmol CO, liberated/mg protein/mm. b Values represent geometric means and 95% confidence limits ( ). ’ Putrescine and polyamine levels are expressed as nmol/mg protein.

(4.6 -10) (6.6 -15) (4.8 - 6.6)

26 (17 -40) 15 (6.5 -35) 2.3 (1.3 - 4.1)

Spermidine VL LL Kidney

1.5 (1.1 - 2.1) 0.49 (0.21- 1.1) 0.21 (0.13- 0.35)

14 (12 -17) b 0.35 (0.23- 0.55) 0.40 (0.27- 0.57)

ODC ’ VL LL Kidney

Putrescine ’ VL LL Kidney

Control

Treatment

10 10 5.4

(4.5 -24) (8.1 -13) (4.1 - 7.1)

38 (17 -86) 19 (13 -26) 2.3 (1.5 - 3.3)

2.4 (1.2 - 4.9) 0.53 (0.37- 0.76) 0.30 (0.27- 0.33)

16 (13 -19) 1.9 (1.3 - 2.8) 3.9 (2.1 - 7.2)

Indomethacin + prolactin

5.9 4.9 5.9

(4.6 - 7.5) (3.2 - 7.4) (3.8 - 9.1)

22 (17 -30) 9.9 (5.7 -17) 2.3 (1.6 - 3.5)

2.0) 1.4) 1.4)

(1.7 -12) (0.85- 1.4) (0.50- 2.2)

1.3 (0.920.82 (0.480.95 (0.66-

4.5 1.1 1.1

Cycloheximide

(3.0 - 6.8) (1.2 - 2.5) (0.8 - 1.2)

6.5 4.2 4.7

(5.1 - 8.3) (3.2 - 5.5) (4.1 - 5.4)

29 (25 -33) 7.3 (5.3 -10) 1.9 (1.7 - 2.2)

1.7 (1.1 - 2.5) 1.1 (0.73- 1.8) 0.83 (0.76- 0.91)

4.5 1.8 1.0

Cycloheximide + prolactin

EFFECTS OF INDOMETHACIN (1 mg) AND CYCLOHEXIMIDE (0.5 mg) ON THE IN VIVO RESPONSE OF THE ORNITHINE DECARBOXYLASE (ODC) TO PROLACTIN (1 mg) AND THE TISSUE CONCENTRATIONS OF PUTRESCINE AND THE POLYAMINES IN THE VENTRAL LOBE (VL) AND LATERAL LOBE (LL) OF THE RAT PROSTATE AND IN THE KIDNEY

TABLE 3

P

95

LL

Kidney

l/lA-

I!0 0

200

400

600

800

1000

PROLACTIN Qg> Fig. 2. Dose-related hypophysectomized geometric

bars are 95% confidence

200

400

600

800

1000

PROLACTIN $g>

alterations in omithine decarboxylase rats (five animals per group) after

means and vertical

0

(ODC) activation in the lateral lobes (LL) and kidneys single S.C. injections of ovine prolactin (50-1000 gg).

of androgenizedValues represent

limits.

Discussion Previous studies have demonstrated that prolactin specifically stimulates the weight and citric acid content of the lateral lobe of the rat prostate (Grayhack, 1963; Prins and Lee, 1983). The present study provides evidence that the same hormone modulates the polyamine system in this lobe. It does so by selectively increasing the activity of at least one of the enzymic steps in the polyamine pathway - the ODC. This interaction has also been reported in other rat tissues including mammary gland and kidney (Richards, 1975; Rillema, 1976), but has never been documented in the prostate. However, the fact that the degree to which the lateral lobe enzyme responded to prolactin differed in the various studies (2.5 to l-fold), emphasizes that this response is probably an expression of the interaction between prolactin and androgens on the lobe, and not simply elicited by prolactin alone. This involvement of other hormones in the regulation of the polyamine pathway may also explain why, in intact rats, prolactin can increase the polyamine concentrations in the ventral lobe after 12 h (Rui et al., 1985) whereas in the hypophysectomized animals of the present study a similar effect could not be

obtained. In confirmation of reports in other target organs (Richards, 1975), the response of the ODC to prolactin was relatively rapid (within 6 h), and was dose-dependent and lasted over 24 h after a single injection. In contrast, the ODC of the other prostatic lobes in the same animal was unaffected by the hormone treatment. Previous reports have also shown that prolactin fails to elicit changes in the citric acid content of the ventral lobe tissue as it does in the lateral lobe (Grayhack, 1963; Slaunwhite and Sharma, 1977). With regard to the rapidity of the response of the enzyme, it is of interest that the same time relationships are associated with the androgen-induced increase observed in the activity of the ODC in the ventral lobe (Pegg et al., 1970). This suggested that these hormones may exert their effects through similar mechanisms. The finding that the response to prolactin cannot be counteracted by indomethacin in the kidney and lateral lobe, suggests that prostaglandins do not mediate the effects of the hormone, at least on this aspect of cellular biochemistry. Indeed, previous studies have provided evidence that prolactin rapidly stimulates the tissue levels of prostaglandins in the human prostate (Farnsworth, 1980), and our own studies in the ventral lobe of

the rat prostate have suggested an interrelationship between these hormones at the membrane level (Rui et al., 1984). Tbe significance of this activation of prostaglandin synthesis is at the present time unknown On the other hand, the indometha~i~-indu~ increase in the basal activity of the ODC in both kidney and lateral lobe tissues, implies that under normal conditions prostaglandins may exert at least a degree of control over the activity of the enzyme. The effects of ~y~lohe~~de on the response of the enzyme were more difficult to interpret, The relative response of the enzyme to prolactin was reduced in the lateral lobe and abolished in the kidney, suggesting that protein synthesis is necessary for the response to be elicited. This confirmed several previous studies in other tissues {for review, see Tabor and Tabor, 1976). One possibility is that the drug exerts some of its effects also indirectly by reducing the number of newly synthesized prolactin receptors on the membrane, assuming that such a rapid receptor turnover exists_ Such a reduction could theoretically also explain the reduced response of the lateral lobe cell to the hormone. However, in the present study the animals received cycloheximide just prior to prola&in, too short a time for the drug to influence the receptor levels. The effects of the drug on the basal activity of the enzyme differed between the tissues. The drastic reduction in basal activity after only 8 h in the ventral lobe, suggests that a high level of protein synthesis is necessary to sustain the high activity of the enzyme in this lobe. In contrast, in the kidney and lateral lobe, the basal activity was enhanced by the drug. Rebound effects (after 8 h of injection) of cycloheximide have been reported in rat liver (Levine et al., 1975). Moreover, one theory of ODC activation is that it may involve the removal of an inhibitor whose synthesis may be ~y~lohe~~de-sensitive (Heller et al., 1976). If the latter explanation is confirmed, such data would imply that the ODC can be activated via several mechanisms even with the same hormone. Comparison of the effects of cycloheximide in the different tissues suggested that the synthesis of spermidine and spermine were also differentially affected by inhibiting protein synthesis, depending on which organ was

examined. Whereas the drug had no effect on the endogenous levels of these amines in the kidney and the ventral lobe, their production in the lateral lobe appeared to be inhibited. This indicates that the enzymes responsible for their biosynthesis, the spermidine and spermine synthases, may be more sensitive to the drug in the lateral lobe than in the other tissues, for reasons which are as yet unclear. A general impression which can be gleaned from the different studies is that the UDC has to be stimulated at least 3-fold before changes are observed in its product, putrescine. However, this enzyme is only one step in a biosynthetic pathway and the levels of this amine are a balance between synthesis and conversion to the next product in the sequence, and such data can therefore be difficult to interpret. Are these alterations in ODC and putrescine evidence that prolactin exerts its effects on RNA and protein synthesis via this mediating pathway? Polyamines have been used as indicators of cellular growth because their levels increase during growth processes and because these organic cations are believed to interact with nucleic acids and proteins (Ianne et al., 1978). Certainly, the increase in the weight of the lateral lobe, but not ventraf lobe after prolactin treatment, appeared to follow the pattern of activation of the ODC. On the other hand, the polyamines also have an acknowledged role as secretory products in the prostate. This function, however, may be primarily associated with the ventral and dorsal lobes since the endogenous levels of these amines and the activity of the ODC in these tissues are far greater than those in the lateral lobes (Rui et al., 1986). In summary, the present study provides a biochemical endpoint for the action of prolactin in the rat prostate which could facilitate a greater understanding of the mechanisms of its action in this gland and provide a means of exploring its effects. Acknowledgements

These studies have been supported by ‘Landsforeningen mot Kreft’. H.R. has a NAVF scholarship. We thank Veronica Eibakk for skillful technical assistance.

91

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Oka, T. and Perry, J.W. (1976) Biol. Chem. 251, 1738-1744. Pegg, A.E., Lockwood, D.H. and Williams-Ashman, H.G. (1970) B&hem. J. 117,17-34. Prins, G.S. and Lee, C. (1983) Biol. Reprod. 29, 938-945. Richards, J.F. (1975) B&hem. Biophys. Res. Commun. 63, 292-299. Rillema, J.A. (1976) Endocr. Res. Commun. 3, 296-305. Rothblum, L.I., Devlin, T.N. and Ch’ih, J.J. (1976) Biochem. J. 156, 151-157. Rui, H., Gordeladze, J.O., Gautvik, K.M. and Purvis, K. (1984) Mol. Cell. Endocrinol. 38, 53-60. Rui, H., Haug, E., Mevag, B., Thomassen, Y. and Purvis, K. (1985) J. Reprod. Fertil. 75, 421-432. Rui, H., Brekke, I., Msrk& L. and Purvis, K. (1986) AndroIogia, in press. Russell, D.H. (1980) Pharmacology 20, 117-129. Slaunewhite, W.R. and Sharma, M. (1977) Biol. Reprod. 17, 489-492. Syms, A.J., Harper, M.E. and Griffiths, K. (1985) Prostate 6, 145-153. Tabor, C.W. and Tabor, H. (1976) Annu. Rev. B&hem. 45, 285-305.