Urinary excretion of the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in rats

1997 ◽  
Vol 153 (3) ◽  
pp. 411-421 ◽  
Author(s):  
W Klootwijk ◽  
R D H de Boer ◽  
E Sleddens-Linkels ◽  
S M Cockle ◽  
W W de Herder ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Anterior Pituitary ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Female Rats ◽  
Male Rats ◽  
Rat Tissues ◽  
Rat Serum ◽  
Methanolic Extracts ◽  
Gonadotrophin Secretion

Abstract TRH-like immunoreactivity (TRH-LI) was estimated in methanolic extracts of rat tissues and blood by RIA using antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2, or antiserum 8880, which is specific for TRH (pGlu-His-ProNH2). TRH-LI (determined with antiserum 4319) and TRH (determined with antiserum 8880) contents were 8 and 8 ng/g in brain, 216 and 222 ng/g in hypothalamus, 6·5 and 6 ng/g in pancreas, 163 and 116 ng/g in male pituitary, 105 and 77 ng/g in female pituitary, 1 and 0·1 ng/g in salivary gland, 61 and 42 ng/g in thyroid, 12 and 3 ng/g in adrenal, 3 and 0·3 ng/g in prostate, and 11 and 0·8 ng/g in ovary respectively. Blood TRH-LI (antiserum 4319) and TRH (antiserum 8880) levels were 31 and 18 pg/ml in male rats, and 23 and 10 pg/ml in female rats respectively. Unextracted serum obtained from blood kept for at least 1 h at room temperature no longer contained authentic TRH but still contained TRH-LI (males 20·3 ± 3·1, females 15·9 ± 3·0 pg/ml; means ± s.e.m.). Isocratic reverse-phase HPLC showed that TRH-LI in serum is largely pGlu-Glu-ProNH2 (<EEP-NH2), a peptide previously found in prostate and anterior pituitary. In urine, TRH-LI (antiserum 4319) and TRH (antiserum 8880) levels were 3·21 ± 0·35 and 0·32 ± 0·04 ng/ml in male rats and 3·75 ± 0·22 and 0·37 ± 0·04 ng/ml in female rats respectively (means ± s.e.m.). Anion-exchange chromatography on QAE-Sephadex showed that urine of normally fed rats contains both basic/neutral TRH-LI (b/nTRH-LI) and acidic TRH-LI (aTRH-LI) in a ratio of ≈ 40:60, and further analysis by HPLC indicated that aTRH-LI represents <EEP-NH2. Analysis of food extracts and urine from fasted rats demonstrated that b/nTRH-LI is derived from food particles spilled by the rats during urine collection, while aTRH-LI is endogenously produced. While urinary aTRH-LI levels were higher in female than in male rats (2·99 ± 0·41 vs 2·04 ± 0·20 ng/ml), the daily urinary excretion was similar in both sexes (females 15·6 ± 1·4, males 19·5 ± 2·0 ng/day). Intravenously injected <EEP-NH2 disappeared from serum with a half-life of ≈ 1 h, and was recovered unchanged and quantitatively in urine. In contrast, when <EEP-NH2 was administered with food, only ≈ 0·5% was recovered in urine. The urinary clearance rate of serum TRH-LI amounted to 0·52 ± 0·10 ml/min in males and 0·34 ± 0·05 ml/min in females. In view of the presence of <EEP-NH2 in the anterior pituitary gland, and the regulation of its content in parallel with gonadotrophins, we examined the possibility that serum <EEP-NH2 is of pituitary origin and correlates with gonadotrophin secretion. However, treatments that alter pituitary <EEP-NH2 content and gonadotrophin release had no effect on serum TRH-LI or urinary aTRH-LI. In conclusion, the TRH-like peptide <EEP-NH2 is present in rat serum and is excreted into the urine. Moreover, <EEP-NH2 in serum and urine is not derived from rat food and is probably not of pituitary origin. Journal of Endocrinology (1997) 153, 411–421

Regulation of the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in the rat anterior pituitary gland

1995 ◽  
Vol 145 (1) ◽  
pp. 43-49 ◽  
Author(s):  
J M M Rondeel ◽  
W Klootwijk ◽  
E Linkels ◽  
G A C van Haasteren ◽  
W J de Greef ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Sex Difference ◽  
Anterior Pituitary ◽  
Biological Significance ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Anterior Pituitary Gland ◽  
Female Rats ◽  
Male Rats ◽  
Rat Pituitary

Abstract TRH-like peptides share the N- and C-terminal amino acids with TRH (pGlu-His-Pro-NH2) but differ in the middle amino acid residue. One of them, pGlu-Glu-Pro-NH2 (<EEP-NH2; EEP) is present in the rat pituitary gland, but its biological significance is unknown. We investigated the localization and regulation of this tripeptide in the rat pituitary gland. To distinguish between TRH and EEP two antisera were used for RIA: specificity of antiserum 4319 for the TRH-like peptides pGlu-Phe-Pro-NH2 and EEP was equal to or greater than that for TRH, whereas antiserum 8880 is TRH-specific. Our RIA data showed the presence of a TRH-like peptide in the anterior pituitary gland (AP) and of TRH in the posterior pituitary gland (PP). The TRH-like peptide in the AP was identified on anion-exchange chromatography and subsequent HPLC as EEP. Pathophysiological conditions such as altered thyroid and adrenal status and suckling did not affect pituitary gland levels of EEP. In general, however, there is a clear sex difference: levels of EEP are higher in male than in female rats. In both sexes gonadectomy leads to a substantial two- to threefold rise in EEP levels, abolishing the sex difference. Testosterone administration to gonadectomized male rats normalizes levels of EEP again. Disulfiram, an inhibitor of the enzyme peptidylglycine α-amidating monooxygenase, reduced levels of EEP in the AP by approximately 50%. In conclusion: 1) the TRH-like peptide EEP is present in the AP, whereas TRH is confined to the PP, 2) levels of EEP in the AP are regulated by sex steroids, 3) EEP is actively amidated in the AP and thus seems to be produced from a glycine-extended progenitor sequence. Journal of Endocrinology (1995) 145, 43–49

Gender difference in the Oatp1-mediated tubular reabsorption of estradiol 17β-d-glucuronide in rats

2002 ◽  
Vol 282 (6) ◽  
pp. E1245-E1254 ◽  
Author(s):  
Yasumasa Gotoh ◽  
Yukio Kato ◽  
Bruno Stieger ◽  
Peter J. Meier ◽  
Yuichi Sugiyama
Keyword(s):  
Gender Difference ◽  
Urinary Excretion ◽  
Glomerular Filtration ◽  
Hormonal Regulation ◽  
Organic Anion ◽  
Female Rats ◽  
Male Rats ◽  
Control Male ◽  
Male And Female Rats ◽  
Estradiol 17Β

The gender difference in the urinary excretion of estradiol-17β-glucuronide (E2-17βG) was examined in rats. The urinary clearance of E2-17βG was >250 times lower in male than in female rats. No such major gender difference was observed in its biliary excretion or metabolism in kidney homogenate. Both plasma protein binding and inulin clearance were comparable in male and female rats, suggesting that this gender difference cannot be explained by glomerular filtration. The urinary clearance with respect to the plasma unbound E2-17βG in male rats was <1% of the glomerular filtration rate, indicating its potential reabsorption by the kidney, and this increased to a level comparable with that found in female rats when dibromosulfophthalein was coinfused. A marked increase in E2-17βG urinary excretion was also observed in male rats that had undergone orchidectomy. Testosterone injections given to female rats reduced the urinary excretion to a level comparable with that of control male rats. The concomitant change in the expression of the gene product for organic anion-transporting polypeptide Oatp1, of which E2-17βG is a typical substrate, was found in the kidney membrane fractions after these treatments. These results suggest that urinary E2-17βG excretion is subject to hormonal regulation and that the large gender difference can be explained by regulation in Oatp1-mediated reabsorption.

Aniline hydroxylation and 7-ethoxycoumarin O-deethylation activities in solubilized and partially resolved liver cytochromes P-450 from ethanol-fed rats

1984 ◽  
Vol 62 (3) ◽  
pp. 266-271 ◽  
Author(s):  
V. Plourde ◽  
C. Hétu ◽  
J.-G. Joly
Keyword(s):  
Liver Microsomes ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Female Rats ◽  
Ethanol Administration ◽  
Molar Activity ◽  
Acidic Fraction ◽  
Chronic Ethanol Administration ◽  
And Control ◽  
Cytochrome P 450

Chronic ethanol administration in female rats enhances the apparent molar activity of liver microsomes for aniline hydroxylation and 7-ethoxycoumarin O-deethylation. Microsomal cytochromes P-450 from ethanol-fed and control rats have been solubilized and partially resolved in six fractions by anion-exchange chromatography. Induction of aniline hydroxylase activity by ethanol was associated with marked increases in the turnover numbers of the more basic cytochrome P-450 containing fractions in a reconstituted aniline hydroxylation system. Cytochrome P-450, exhibiting by far the highest 7-ethoxycoumarin O-deethylase activity, was eluted in a relatively acidic fraction; its turnover number with 7-ethoxycoumarin after ethanol consumption, however, did not differ significantly from that of the corresponding fraction from control microsomes. These observations suggest that induction of liver microsomal mixed function oxidases by ethanol may reflect the contribution of more than one cytochrome P-450 isozyme.

THE MECHANISM OF THE INDUCTION OF OVULATION BY OESTROGENS

1965 ◽  
Vol 33 (3) ◽  
pp. 491-499 ◽  
Author(s):  
F. DÖCKE ◽  
G. DÖRNER
Keyword(s):  
Effective Dose ◽  
Corpus Luteum ◽  
Anterior Pituitary ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Main Site ◽  
Induction Of Ovulation ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Electrolytic Lesions

SUMMARY To study the positive feed-back mechanism by which oestrogen induces corpus luteum formation, electrolytic lesions were placed in different parts of the anterior hypothalamus of prepubertal female rats which were then injected with oestradiol benzoate. Ovarian luteinization did not occur when the main parts of the suprachiasmatic nuclei or of the medial preoptic area had been destroyed. Oestradiol benzoate was implanted stereotaxically into the brain and the anterior pituitary of immature female rats. Whereas 1/25 of the subcutaneously effective dose had to be implanted into the anterior hypothalamus, 1/100 of the peripherally effective dose introduced into the adenohypophysis was sufficient to induce corpus luteum formation in most of the treated animals. The results suggest that, although the anterior hypothalamus is necessary for this positive feed-back mechanism, the anterior pituitary may be the main site of action of oestrogen. Oestrogen may increase the hypophysial sensitivity to the hypothalamic gonadotrophin-releasing factor. Thus an enhanced gonadotrophin secretion may result, sufficient for the induction of ovulation. The possibility is discussed that this positive feed-back mechanism is also essential for the induction of ovulation in women.

scholarly journals Effect of Exogenous Melatonin Treatment on the Reproductive Characteristics and Progeny of Male Rats Exposed to Different Periods From Light and Darkness

2017 ◽  
pp. 507-518 ◽  
Author(s):  
K. A. A. MAJRASHI ◽  
I. A. H. BARAKAT ◽  
A. R. AL-HIMAIDI ◽  
K. G. ADHAM
Keyword(s):  
Hormone Treatment ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Testis Weight ◽  
Melatonin Treatment ◽  
Rat Serum ◽  
Exogenous Melatonin ◽  
Anti Oxidant ◽  
Harmful Effects

Light is an important environmental factor that controls the regulation of physiological functions of organisms. Melatonin is considered as one of the major hormones that play an important role in protecting body from many harmful effects and acts as a powerful anti-oxidant source to controlling the levels of antioxidant enzymes within the body. The main objectives of this work were to study the effect of 1) photoperiod changes and 2) exogenous melatonin hormone treatment on the sperm properties, body and testis weight, embryo characteristics, and concentration level of melatonin and testosterone in treated rat serum. This study has been conducted using thirty-six male rats and one hundred and twenty female rats. Animals were divided into six groups, each group containing six males and twenty female rats. Our results showed a significant influence of photoperiod changes on the melatonin and testosterone hormones concentration in rats’ serum, body weight only, while the other characteristics not affected. As for the effect of melatonin it has been found that the movement of sperm in GIII and IV, as well as embryos absorbed and newborns weight traits has been significantly affected, while the rest of the properties were not significantly affected by melatonin treatment.

ROLE OF OESTROGENS AND GONADOTROPHINS IN PERPHENAZINE-INDUCED MAMMOGENESIS

1970 ◽  
Vol 48 (3) ◽  
pp. 365-371 ◽  
Author(s):  
A. DANON ◽  
C. P. WELLER ◽  
F. G. SULMAN
Keyword(s):  
Median Eminence ◽  
Mammary Glands ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Gonadotrophin Secretion

SUMMARY Treatment of intact or recently (1 day) ovariectomized female rats with 5 mg perphenazine (Trilafon)/kg/day for 5 days resulted in marked lobulo—alveolar differentiation of the mammary glands. Perphenazine failed to stimulate mammogenesis in chronically (12 days) ovariectomized rats, unless they had been primed with oestradiol. However, mammogenic effects in chronically ovariectomized rats were obtained after implantation of minute amounts (2 μg) of oestradiol into the median eminence, or after treatment for 16 days with the non-steroid pituitary gonadotrophin-inhibitor methallibure (ICI 33828; 20 mg/kg/day). Since these latter procedures counteract the gonadotrophin surge after ovariectomy, it would appear that inhibition of gonadotrophin secretion is necessary before prolactin secretion can be stimulated by perphenazine. Castrated male rats responded to perphenazine with lobulo—alveolar differentiation similar to that in intact males. The implications of this difference with regard to the mechanism of pituitary response to gonadectomy are discussed.

scholarly journals Comparison of the activities of a multiple inositol polyphosphate phosphatase obtained from several sources: a search for heterogeneity in this enzyme

1995 ◽  
Vol 305 (2) ◽  
pp. 491-498 ◽  
Author(s):  
A Craxton ◽  
N Ali ◽  
S B Shears
Keyword(s):  
Molecular Mass ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Polyclonal Antiserum ◽  
Apparent Molecular Mass ◽  
Size Exclusion ◽  
Rat Tissues ◽  
Inositol Polyphosphate ◽  
Phosphatase Activities ◽  
Specific Activities

A multiple inositol polyphosphate phosphatase (formerly known as inositol 1,3,4,5-tetrakisphosphate 3-phosphatase) was purified approx. 22,000-fold from rat liver. The final preparation migrated on SDS/PAGE as a doublet with a mean apparent molecular mass of 47 kDa. Upon size-exclusion chromatography, the enzyme was eluted with an apparent molecular mass of 36 kDa. This enzyme was approximately evenly distributed between the ‘rough’ and ‘smooth’ subfractions of endoplasmic reticulum. There was a 20-fold range of specific activities of this phosphatase in CHAPS-solubilized particulate fractions prepared from the following rat tissues: liver, heart, kidney, testis and brain. However, each of these extracts contained different amounts of endogenous inhibitors of enzyme activity. After removal of these inhibitors by MonoQ anion-exchange chromatography, there was only a 2.5-fold range of specific activities; kidney contained the most and brain contained the least. We prepared and characterized polyclonal antiserum to the hepatic phosphatase, which immunoprecipitated 85-100% of both particulate and soluble phosphatase activities. The antiserum also immunoprecipitated, with equivalent efficacy, CHAPS-solubilized phosphatase activities from heart, kidney, testis, brain and erythrocytes (all prepared from rat). Our data strengthen the case that the function of the mammalian phosphatase is unrelated to the metabolism of Ca(2+)-mobilizing cellular signals. The CHAPS-solubilized phosphatase from turkey erythrocytes was not immunoprecipitated by the polyclonal antiserum, and is therefore an isoform that is structurally distinct, and possibly functionally unique.

Effects of neonatal androgenization on the chromatofocusing pattern of anterior pituitary FSH in the female rat

1990 ◽  
Vol 126 (2) ◽  
pp. 323-332 ◽  
Author(s):  
A. Ulloa-Aguirre ◽  
P. Damián-Matsumura ◽  
R. Espinoza ◽  
R. Dominguez ◽  
L. Morales ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Female Rats ◽  
Size Exclusion ◽  
Male Rats ◽  
Female Rat ◽  
Adult Males ◽  
Multiple Forms ◽  
Alkaline Region ◽  
Pituitary Glands ◽  
Ph Range

ABSTRACT Anterior pituitary glands were removed from neonatally androgenized (100 μg testosterone propionate) female rats and normal controls at 5, 10, 18, 21, 30, 60 and 90 days of age, and the multiple forms of FSH present within them were separated by chromatofocusing (pH range 7·5–4·0). Additional pituitary glands from intact adult males (90 days old) were also studied for comparative purposes. All animal groups exhibited multiple forms of immunoactive FSH within a pH range of 7·5–4·0, as well as an additional FSH form obtained after the addition of 1·0 mol NaCl/l to the chromatofocusing column (salt peak). In animals 5–30 days old (controls and androgenized) the majority of FSH applied to the chromatofocusing columns was recovered within the salt peak (45-85% of total FSH immunoactivity recovered). However, as the animals aged, more FSH immunoactivity focused within less acidic regions (isoelectric point (pI) 5·9–5·0); pituitaries from animals 60 days old contained the greatest proportion of FSH focused within this pH range (controls, 39·2±0·6%; androgenized, 23·1 ±0·9% of total immunoactivity recovered; P < 0·03 vs animals 30 days old for both experimental groups). This shift towards less acidic FSH was attenuated in androgenized animals compared with the controls (P<0·01). In control adult rats, the chromatofocusing distribution pattern of pituitary FSH varied according to the day of the oestrous cycle. Pituitary extracts from control rats decapitated during the morning of pro-oestrus, oestrus and day 1 of dioestrus exhibited the highest proportion of immunoactive FSH (23·2–28·8% of total) focused within a pH range of 5·9–5·0, whilst only 10·4–11·6% of FSH from androgenized rats and those on day 1 of dioestrus was recovered within this pH range (P<0·05). In control animals decapitated during the morning of prooestrus and oestrus, 10–26% of FSH focused within the most alkaline region (pI 7·5–6·0); the chromatofocusing pattern of pituitary FSH from the neonatally androgenized animals was characteristic, in that no more than one peak (1·5±0·5% of total) was detected in this alkaline region. In the adult male rats, the majority of pituitary FSH eluted from the chromatofocusing columns within a pH of 4·9–4·0 (52·4±1·2% of total FSH immunoactivity) and the salt peak (pH <4·0) (33·1 ±2·4 of total). All FSH isoforms obtained after chromatofocusing represented α and β dimers as disclosed by size exclusion chromatography. The results strongly suggest that a cyclic or 'female' pattern of hypothalamic and gonadal secretion leads the anterior pituitary towards the production of less acidic FSH isoforms, whereas a tonic or 'androgenic' type of secretion, as that present in adult males and females with the androgen-induced anovulatory syndrome, leads more to the production of strongly acidic FSH isoforms. The finding of qualitative and quantitative differences among normally cycling and androgenized animals gives further support for the concept of the existence of a sexual dichotomy in terms of the type of FSH synthesized by the anterior pituitary gland. Journal of Endocrinology (1990) 126, 323–332

RELATIONSHIP BETWEEN THE PITUITARY GLAND AND GONADAL STEROIDS: INVOLVEMENT OF A HYPOPHYSIAL FACTOR IN REDUCED α2u-GLOBULIN AND INCREASED TRANSCORTIN CONCENTRATIONS IN RAT SERUM

1978 ◽  
Vol 78 (1) ◽  
pp. 31-38 ◽  
Author(s):  
G. VANDOREN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN ◽  
P. DE MOOR
Keyword(s):  
Pituitary Gland ◽  
Testosterone Propionate ◽  
Single Injection ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Male Rats ◽  
Rat Serum ◽  
Mediated Effects ◽  
Male And Female Rats ◽  
Oestradiol Benzoate

Evidence is presented that the level of α2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats α2u-globulin cannot be detected. Moreover, α2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of α2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of α2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of α2u-globulin.

Serotonin induces gonadotrophin release through stimulation of LH-releasing hormone release from the median eminence

1986 ◽  
Vol 111 (2) ◽  
pp. 309-315 ◽  
Author(s):  
M. L. Vitale ◽  
M. N. Parisi ◽  
S. R. Chiocchio ◽  
J. H. Tramezzani
Keyword(s):  
Median Eminence ◽  
Anterior Pituitary ◽  
Female Rats ◽  
Male Rats ◽  
Tissue Samples ◽  
Releasing Hormone ◽  
The Third ◽  
Lh Releasing Hormone ◽  
Perifusion System

ABSTRACT The effects of serotonin (5-HT) on the release of gonadotrophins and LH-releasing hormone (LHRH) were examined in an in-vitro perifusion system using median eminences and/or anterior pituitaries obtained from male or pro-oestrous female rats. Animals were killed by decapitation between 12.00 and 13.00 h. A serial double-chamber perifusion system was employed. Three types of experiments were performed. In the first, median eminences were placed in the first chamber and one anterior pituitary in the second chamber. In the second group, only the anterior pituitary was perifused. In the third group, only five median eminences were perifused. In the first and second experiments, LH, FSH and prolactin were determined in the perifusion efflux by radioimmunoassay (RIA). In the third experiment, LHRH was determined by RIA. Addition of 5-HT (final concentrations 0·06, 0·6 and 6·0μmol/l) into the first chamber containing the median eminences stimulated the release of LH and FSH from the pituitary, but did not affect the levels of prolactin in the effluent in the same experiment (prooestrous rats). The stimulatory effect of 5-HT was blocked by the addition of cyproheptadine (1 μmol/l) in the perifusion fluid. The introduction of 5-HT (0·6 μmol/l) into the tube connecting the first and second chambers did not modify the release of LH, nor did 5-HT added to the pituitaries perifused alone. Injection of 5-HT into the first chamber (median eminences), containing tissue samples from male rats, stimulated LH release, but to a significantly (P< 0·001) lower degree than that found when samples from pro-oestrous females were used (P< 0·0001). When median eminences from pro-oestrous rats were perifused alone, injection of 5-HT produced an immediate release of LHRH which peaked during the first 10 min of collection and lasted for 30 min; in these experiments, a clear relationship existed between dose of 5-HT and release of LHRH (P<0·02). The stimulatory effect of 5-HT was blocked by the addition of cyproheptadine (5 μmol/l) or methiothepin (5 μmol/l). These results demonstrate that 5-HT stimulates gonadotrophin release by acting directly on LHRH terminals in the median eminence from pro-oestrous rats. Furthermore, the effect of 5-HT on LHRH release was dose dependent and was nullified by 5-HT receptor blockers (cyproheptadine and methiothepin). J. Endocr. (1986) 111, 309–315

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