A model for studies on the response of the ventral prostate to oestrogens

1981 ◽  
Vol 97 (1) ◽  
pp. 125-136 ◽  
Author(s):  
J. J. Corrales ◽  
P. A. Høisaeter ◽  
N. Kadohama ◽  
G. P. Murphy ◽  
A. A. Sandberg
Keyword(s):  
Body Weight ◽  
Organ Culture ◽  
Age Differences ◽  
Oestrogen Receptor ◽  
Direct Interaction ◽  
Ventral Prostate ◽  
Target Tissue ◽  
The Mean ◽  
In Vivo Effects

Abstract. The effects of oestrogen administration on the weight of ventral and dorsolateral prostates were studied in castrated rats of Wistar-Furth and Copenhagen strains. Direct effect of oestradiol (Oe2) on prostatic tissue was also investigated in organ culture. Oe2-treated animals received daily injections of 50 μg for 7 days. Control animals were treated with the vehicle only (peanut oil). In 4 month old Copenhagen rats the mean weight of the ventral prostates (42.4 ± 9.4 mg/100 g body weight) was significantly higher than that in the control animals (19.9 ± 4.6 mg/100 g body weight, P < 0.0001). No such differences were observed in older Copenhagen rats (9 months old) or Wistar-Furth rats (3 and 6 months old). Thus, this effect of Oe2 on ventral prostate seems both strain specific and age specific. Similar strain and age differences in the Oe2 effect were found in the dorsolateral prostate, but to a smaller extent. Direct interaction of Oe2 with target tissue was demonstrated in culture as evidenced by the ability of the steroid to prevent regression in explants derived from prostates of Copenhagen rats. The in vivo effects of Oe2 on the prostate weights could not be explained by differences in specific androgen or oestrogen receptor contents or in testosterone (T) metabolism. However, the prostates of younger Copenhagen rats differed from those of all other groups in three respects: 1) they contained high levels of oestramustine binding protein (OeBP), 2) they had the highest amount of uptake of radioactivity into the nuclear residue, and 3) their histological picture was characterized by diffuse stromal architecture having the appearance of oedematous tissue.

THE INFLUENCE OF SERUM ON THE UPTAKE, CONVERSION AND ACTION OF DIHYDROTESTOSTERONE IN RAT PROSTATE GLANDS IN ORGAN CULTURE

1975 ◽  
Vol 64 (2) ◽  
pp. 289-297 ◽  
Author(s):  
ILSE LASNITZKI ◽  
HILARY R. FRANKLIN
Keyword(s):  
Organ Culture ◽  
Horse Serum ◽  
Target Tissue ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free ◽  
Human Pregnancy ◽  
Human Male ◽  
Columnar Cells

SUMMARY The influence of serum on the uptake, conversion and action of dihydrotestosterone in relation to the sex steroid binding protein, TeBG, has been investigated in rat ventral prostates in organ culture. The organs were incubated with [1,2-3H]dihydrotestosterone in: (1) serum-free medium, (2) horse serum, foetal and newborn bovine serum or (3) human male and human pregnancy serum. With all sera the uptake of dihydrotestosterone fell with rising serum concentration, at first steeply and then more gradually. At the same concentration, the uptake was significantly lower in explants incubated with human pregnancy serum than in those kept with human male serum. The conversion of dihydrotestosterone to androstanediol followed the same pattern and less androstanediol was formed in the presence of pregnancy serum. Since pregnancy serum contains higher amounts of TeBG than male serum, the lowered uptake suggests that only the free hormone was available to the target organ. Addition of unlabelled dihydrotestosterone resulted in a higher uptake than that measured in explants incubated with the labelled steroid only. The effect of the human sera on uptake and conversion was correlated with the androgenic activity of dihydrotestosterone applied at physiological concentrations and expressed as the percentage of secretory columnar cells present. The degree of maintenance closely corresponded to the uptake of the hormone. In serum-free medium, the number of columnar cells approached the values found in vivo, with male serum their number, though reduced, was still substantial, with pregnancy serum it was extremely low. It is concluded that the amounts of TeBG present in serum regulate the supply of the hormone to the target tissue and thus control its biological action.

scholarly journals In VivoEffects of Leptin-Related Synthetic Peptides on Body Weight and Food Intake in Female ob/obMice: Localization of Leptin Activity to Domains Between Amino Acid Residues 106–140*

Endocrinology ◽  
1997 ◽  
Vol 138 (4) ◽  
pp. 1413-1418 ◽  
Author(s):  
Patricia Grasso ◽  
Matthew C. Leinung ◽  
Stacy P. Ingher ◽  
Daniel W. Lee
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Amino Acid ◽  
Food Intake ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Amino Acid Residues ◽  
Inactive Form ◽  
In Vivo Effects

Abstract In C57BL/6J ob/ob mice, a single base mutation of the ob gene in codon 105 results in the replacement of arginine by a premature stop codon and production of a truncated inactive form of leptin. These observations suggest that leptin activity may be localized, at least in part, to domains distal to amino acid residue 104. To investigate this possibility, we synthesized six overlapping peptide amides corresponding to residues 106–167 of leptin, and examined their effects on body weight and food intake in female C57BL/6J ob/ob mice. When compared with vehicle-injected control mice, weight gain by mice receiving 28 daily 1-mg ip injections of LEP-(106–120), LEP-(116–130), or LEP-(126–140) was significantly (P &lt; 0.01) reduced with no apparent toxicity. Weight gain by mice receiving LEP-(136–150), LEP-(146–160), or LEP-(156–167) was not significantly different from that of vehicle-injected control mice. The effects of LEP-(106–120), LEP-(116–130), or LEP-(126–140) were most pronounced during the first week of peptide treatment. Within 7 days, mice receiving these peptides lost 12.3%, 13.8%, and 9.8%, respectively, of their initial body weights. After 28 days, mice given vehicle alone, LEP-(136–150), LEP-(146–160), or LEP-(156–167) were 14.7%, 20.3%, 25.0%, and 24.8% heavier, respectively, than they were at the beginning of the study. Mice given LEP-(106–120) or LEP-(126–140) were only 1.8% and 4.2% heavier, respectively, whereas mice given LEP-(116–130) were 3.4% lighter. Food intake by mice receiving LEP-(106–120), LEP-(116–130), or LEP-(126–140), but not by mice receiving LEP-(136–150), LEP-(146–160), or LEP-(156–167), was reduced by 15%. The results of this study indicate 1) that leptin activity is localized, at least in part, in domains between residues 106–140; 2) that leptin-related peptides have in vivo effects similar to those of native leptin; and 3) offer hope for development of peptide analogs of leptin having potential application in human or veterinary medicine.

IN VIVO ANDROGEN BINDING IN RAT SKELETAL AND PERINEAL MUSCLES

1979 ◽  
Vol 91 (2) ◽  
pp. 362-372 ◽  
Author(s):  
France T. Dionne ◽  
Jean Y. Dubé ◽  
Renée L. Lesage ◽  
Roland R. Tremblay
Keyword(s):  
Skeletal Muscles ◽  
Sucrose Gradient ◽  
Reductase Activity ◽  
High Rate ◽  
Ventral Prostate ◽  
Target Tissue ◽  
Thigh Muscles ◽  
Reference Target ◽  
Androgen Binding

ABSTRACT In vivo binding of [3H] testosterone2), [3H]5α-dihydrotestosterone and [3H]3α-androstanediol to cytosolic and nuclear fractions of LA/BC and thigh muscles has been studied in functionally hepatectomized castrated rats following a 1 h infusion of the labelled steroid. The identification of metabolites formed from each steroid has also been determined in tissue cytosols. In each experiment, ventral prostate was used as reference target tissue. After [3H] testosterone and [3H]5α-dihydrotestosterone perfusions, cytosolic binding could be demonstrated in a 8–10S peak on sucrose gradient with LA/BC and ventral prostate or in the macromolecular fraction after filtration through Sephadex G-25 with thigh muscles. In both types of muscles, [3H]5α-dihydrotestosterone binding represented only one tenth of [3H] testosterone binding. This behaviour seems to be related to the high rate of 5α-dihydrotestosterone metabolism observed in these tissues; testosterone, on the contrary, was not metabolized. After [3H]3α-androstanediol perfusion, cytosolic [3H] androgen binding in LA/BC and in thigh muscles was almost non-existent. In muscles [3H]3α-androstanediol remained essentially unconverted. In ventral prostate, with every hormone studied level of cytosolic binding was comparable. It was observed that in this tissue [3H] testosterone and [3H]3α-androstanediol were metabolized into [3H]5α-dihydrotestosterone. Androgen binding to 0.4 m KCl extracted nuclear proteins has been demonstrated in ventral prostate as a 3.5–4.5S binding peak on sucrose gradient and this with each steroid perfused. In LA/BC, only [3H] testosterone gave a well defined binding peak. In thigh muscles, levels of nuclear binding were too low to be determined. In summary, these results suggest that rat perineal and skeletal muscles possess cytosolic androgen binding proteins similar to those found in ventral prostate. However, it appears that steroid metabolism is quite different in ventral prostate and muscles with respect to presence of 5α-reductase activity and extent of conversion of 5α-dihydrotestosterone into androstanediols. These differences may explain why, in vivo, muscles bind testosterone instead of 5α-dihydrotestosterone as in ventral prostate.

Chemopreventive Effect of a Novel Nutrient Mixture on Lung Tumorigenesis Induced by Urethane in Male A/J Mice

2009 ◽  
Vol 95 (4) ◽  
pp. 508-513 ◽  
Author(s):  
M Waheed Roomi ◽  
Nusrath W Roomi ◽  
Tatiana Kalinovsky ◽  
Matthias Rath ◽  
Aleksandra Niedzwiecki
Keyword(s):  
Body Weight ◽  
Control Diet ◽  
Test Group ◽  
Lung Tumors ◽  
Mouse Lung ◽  
Lung Tumorigenesis ◽  
Group A ◽  
The Mean ◽  
Group B

Aims and background Lung cancer, a leading cause of cancer death, is associated with exposure to inhalation carcinogens, most commonly those found in tobacco smoke. We investigated the in vivo effect of dietary supplementation with a nutrient mixture containing lysine, proline, arginine, ascorbic acid, green tea extract, N-acetyl cysteine, selenium, copper and manganese on the development of urethane-induced lung tumors in male A/J mice. Methods After one week of isolation, seven-week-old male A/J mice (n = 25) weighing 17–19 g were randomly divided into three groups: group A (n = 5), group B (n = 10), and group C (n = 10). Mice in groups B and C were each given a single intraperitoneal injection of urethane (1 mg/g body weight) in saline, whereas group A mice received an injection of saline alone. Groups A and B were fed a regular diet, whereas group C was fed the same diet supplemented with 0.5% nutrient mixture. After 20 weeks, mice were sacrificed, lungs were excised and weighed, and tumors were counted and processed for histology. Results Urethane-challenged mice developed tumors. However, the mean number of tumors and the mean lung weights in the mice on the supplemented diet were significantly reduced, by 49% (P <0.0001) and 18% (P = 0.0025), respectively, compared to mice on the control diet. We observed neither significant differences in body weight gains nor in diet consumption among the mice. Pulmonary lesions were morphologically similar for both the groups (adenomas), but lesions were smaller in the test group. Conclusions The results suggest that nutrient mixture has inhibitory potential on the development of mouse lung tumors induced by urethane

Avidin and ovalbumin induction by progesterone in chicken oviduct detected by sensitive immunoenzymometric assays

1991 ◽  
Vol 130 (2) ◽  
pp. 191-197 ◽  
Author(s):  
T. Joensuu ◽  
P. Tuohimaa ◽  
P. Vilja
Keyword(s):  
Body Weight ◽  
Oestrogen Treatment ◽  
Low Concentrations ◽  
Coefficients Of Variation ◽  
Chicken Tissue ◽  
Chicken Oviduct ◽  
Biotin Binding ◽  
The Mean ◽  
Dose Dependent

ABSTRACT This study describes sensitive immunoenzymometric assays (IEMAs) for chicken avidin and ovalbumin, markers of cytodifferentiation and action of progesterone and oestrogen in the oviduct magnum mucosa. The determination range was 0·5–100 ng/ml and the detection limit 0·1 ng/ml in both IEMAs. The intra- and interassay coefficients of variation, measured from chicken tissue supernatants, averaged below 6 and 10% respectively. IEMAs correlated well with the radioimmunoassays for avidin and ovalbumin previously developed in our laboratory, and with the widely used [14C]biotin-binding method for avidin. Using an IEMA, we found avidin induction with low concentrations of progesterone in the differentiated oviduct of oestrogen-pretreated chicks. The induction has not been detected previously by less sensitive methods. Avidin was induced by all given doses of progesterone (0·2–200 mg/kg in vivo for 24 h after a short oestrogen treatment), the response being dose-dependent at doses of 0·2–20 mg progesterone/kg body weight, the maximum avidin production being about 70 μg/g tissue. Ovalbumin was induced at doses of 2–200 mg progesterone/kg body weight without variations in the responses, being about 35 mg/g. The mean content of avidin in the oviduct of laying hens was 58·1 μg/g, and of ovalbumin 74·9 mg/g. Minimal traces of avidin and ovalbumin were found in the oviduct after hatching (0·3 and 5 μg/g respectively); however, progesterone did not have an effect on this expression. Sensitivity, rapidity and practicability, together with non-radioactivity, are the main advantages of the present IEMAs for chicken avidin and ovalbumin. Journal of Endocrinology (1991) 130, 191–197

scholarly journals The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat

2000 ◽  
pp. 273-277 ◽  
Author(s):  
D Hofer ◽  
M Raices ◽  
K Schauenstein ◽  
S Porta ◽  
W Korsatko ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Receptor Agonist ◽  
Wistar Rats ◽  
Type Ii ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Cgp 12177 ◽  
In Vivo Effects

OBJECTIVE: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4) deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT) were assessed in 300 g body weight (BW) Wistar rats. DESIGN: Seven days after SX, groups of rats were implanted s.c. with pellets containing 5mg CGP-12177 or 5mg norepinephrine (NE) and were immediately placed at 4 degrees C for 24h. Other SX groups were injected with CGP-12177 or NE 1mg/kg BW i. p. and placed in the cold for 4h. The latter group was injected, in addition, with prazosin 0.4 mg/100g BW i.p. or propranolol 0.5mg/100g BW i.p. 15 min before and 2h after the administration of CGP-12177 or NE. METHODS: Two hours after the last injection of prazosin or propranolol, animals were killed and BAT was removed, homogenized and centrifuged at 500 g for 10 min at 4 degrees C. The infranatants were incubated during 60 min in the presence of dithiothreitol and 1 microCi [(125)I]T4. Aliquots were chromatographed on paper for the measurement of [(125)I]T4 and its deiodinated subproducts. RESULTS: CGP-12177 restored normal T4 deiodination in SX BAT from both groups, but NE was slightly more effective. Propranolol, although not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in deiodination was blocked by prazosin and to a lesser extent by propranolol. CONCLUSIONS: The results indicate that CGP-12177 stimulated the in vivo activation of 5'-deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.

Effect of theophylline on nuclear retention of oestrogen-receptor complexes: correlation with oestrogen responses

1985 ◽  
Vol 105 (3) ◽  
pp. 397-403
Author(s):  
J. Steinsapir ◽  
A. M. Rojas ◽  
M. E. Bruzzone ◽  
A. White ◽  
O. Alarcón ◽  
...  
Keyword(s):  
Body Weight ◽  
Oestrogen Receptor ◽  
Nuclear Retention ◽  
Adult Rat ◽  
Receptor Complexes ◽  
Wet Weight

ABSTRACT In the ovariectomized adult rat uterine oedema induced by 0·01 and 0·1 μg oestradiol-17β/100 g body weight increased further in the presence of theophylline. Nuclear retention of oestrogen-receptor complexes also increased in response to theophylline both in vivo and in vitro. Theophylline decreased the number of eosinophils in the blood and concurrently decreased oestrogen-induced uterine eosinophilia at doses of 0·001, 0·01, 0·1, 1, 10 or 30 μg oestradiol/100 g body weight, through a mechanism independent of glucocorticoids. There was, therefore, no correlation between changes in the number of uterine eosinophils and changes in uterine wet weight induced by theophylline and oestrogen. It is suggested that the presence of oestrogen-receptor complexes in the nucleus for at least 4 h is a prerequisite for the induction of uterine oedema and growth in the presence of theophylline and oestradiol-17β. J. Endocr. (1985) 105, 397–403

Studies of weaner sheep during and after a period of weight stasis. II.* Body composition

1975 ◽  
Vol 26 (2) ◽  
pp. 355 ◽  
Author(s):  
TW Searle ◽  
NMcC Graham
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Tritiated Water ◽  
Complete Recovery ◽  
The Body ◽  
Similar Weight ◽  
The Mean ◽  
The Relationship ◽  
Weight For Age

Wether sheep (4 months old) were held at 20 kg liveweight by restricted feeding for either 4 or 6 months and then fed ad libitum. Body composition (total water, fat and protein) was estimated monthly from tritiated water (TOH) space measured in vivo, and on three occasions representative animals were slaughtered, minced and analysed. Composition at any given body weight was compared with that previously determined for animals grown without restriction (controls). Sheep slaughtered at the end of the period of weight stasis contained less protein and more water than the controls but contained a similar weight of fat. Previously derived prediction equations estimated water correctly from TOH space in these undernourished sheep, but protein was overestimated by 0.38 kg (17% of the mean) and fat was underestimated by 0.19 kg (10% of the mean). The body composition of animals slaughtered after partial or complete recovery of weight for age was normal for their weight and predictions were accurate. The sequential estimates of composition indicated that although the relationship between fat and weight differed between individuals, at any given body weight above 32 kg compensating animals and controls had a similar composition. *Part I, Aust. J. Agric. Res., 26: 343 (1975).

Prostatic growth and development are regulated by FGF10

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3693-3701
Author(s):  
A.A. Thomson ◽  
G.R. Cunha
Keyword(s):  
Organ Culture ◽  
Seminal Vesicle ◽  
Growth And Development ◽  
Reproductive Tract ◽  
Mesenchymal Cells ◽  
Female Reproductive Tract ◽  
Ventral Prostate ◽  
Serum Free

We have examined the role of Fibroblast Growth Factor 10 (FGF10) during the growth and development of the rat ventral prostate (VP) and seminal vesicle (SV). FGF10 transcripts were abundant at the earliest stages of organ formation and during neonatal organ growth, but were low or absent in growth-quiescent adult organs. In both the VP and SV, FGF10 transcripts were expressed only in a subset of mesenchymal cells and in a pattern consistent with a role as a paracrine epithelial regulator. In the neonatal VP, FGF10 mRNA was expressed initially in mesenchymal cells peripheral to the peri-urethral mesenchyme and distal to the elongating prostatic epithelial buds. At later stages, mesenchymal cells surrounding the epithelial buds also expressed FGF10 transcripts. During induction of the SV, FGF10 mRNA was present in mesenchyme surrounding the lower Wolffian ducts and, at later stages, FGF10 transcripts became restricted to mesenchymal cells subadjacent to the serosa. We investigated whether the FGF10 gene might be regulated by androgens by analysing the levels of FGF10 transcripts in SV and VP organs grown in serum-free organ culture. While FGF10 transcript levels increased after treatment with testosterone in the SV (but not VP), these changes were not sensitive to anti-androgen treatment, and thus it is likely that FGF10 mRNA was not directly regulated by testosterone. Also, FGF10 mRNA was observed in the embryonic female reproductive tract in a position analogous to that of the ventral prostate in males suggesting that FGF10 is not regulated by androgens in vivo. Recombinant FGF10 protein specifically stimulated growth of Dunning epithelial and BPH1 prostatic epithelial cell lines, but had no effect on growth of Dunning stromal cells or primary SV mesenchyme. Furthermore, FGF10 protein stimulated the development of ventral prostate and seminal vesicle organ rudiments in serum-free organ culture. When both FGF10 and testosterone were added to organs in vitro, there was no synergistic induction of development. Additionally, development induced by FGF10 was not inhibited by the addition of the anti-androgen Cyproterone Acetate demonstrating that the effects of FGF10 were not mediated by the androgen receptor. Taken together, our experiments suggest that FGF10 functions as a mesenchymal paracrine regulator of epithelial growth in the prostate and seminal vesicle and that the FGF10 gene is not regulated by androgens

Differential Modulation of Erythrogenic Effects of EPO by Prolonged Administration of Glucocorticoids.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1733-1733
Author(s):  
Zili He ◽  
Maged Khalil ◽  
Srinivas Kodali ◽  
Seema Naik ◽  
Chenthilmuragan Rathnasabapathy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Combined Treatment ◽  
Control Treatment ◽  
Prolonged Treatment ◽  
Sprague Dawley ◽  
Research Committee ◽  
Interesting Phenomenon ◽  
In Vivo Effects

Abstract Glucocorticoids have either stimulatory or inhibitory effects on erythropoesis depending upon the timing and the dosage of their administration. We previously reported cases of enhanced hematopoetic recovery in response to erythropoietin (Epo; Procrit) in patients receiving prolonged treatment of glucocortcoids. To examine the differential roles of glucocorticoids on erythropoiesis in chronic settings, we use a murine model in current study and evaluate erythropoietic responses to Epo for rats receiving higher (loading) or lower (maintenance) dosages of dexamethasone(Dex) for a prolonged period of time. Commercially-obtained adult Sprague-Dawley rats were assigned randomly to DEX, EPO, DEX+EPO, or control groups, and maintained at conditions approved by the institutional Animal Care and Research Committee. Rats in the EPO or DEX+EPO groups received subcutaneous injection of Epo at 70 units/100 grams body weight, once a week, for five week. The animals in the DEX or DEX+EPO group were both divided into two subgroups receiving injection of Dex at either higher doses of 0.4mg/350 grams body weight, or lower doses of 0.02 mg/350 grams body weight, three times a week, for five weeks. The animals were sacrificed at the end of study and peripheral blood and bone marrow were used to evaluate levels of erythropoiesis. Weekly administration of Epo (70 units/100 grams body weight) for five weeks produced enhanced erythropoiesis in the EPO group, resulting in an increase of 10.6% in RBC, and 15.3% increase in hemoglobin (Hb), compared to control. Treatment of rats with higher dosage (0.4 mg/350 g, three times a week for five weeks) of dexamethasone increased RBC and Hb by 3% and 2%, respectively, when compared with controls. Combined treatment of Epo and dexamethasone at the higher dosage enhanced the erythropoiesis, and increased RBC and Hb by 20% and 23%, respectively. In contrast, treatment of rats with a lower maintenance dosage of 0.02 mg/350 g body weight, three times a week for five weeks, peripheral RBC and Hb levels were dropped by 7% and 6%, respectively. Combination of Epo and the lower dosage of dexamethasone could only generate an increase in RBC and Hb of 10% each, displaying suppressing effect of dexamethasone at lower dosage. Bone marrow biopsy revealed hypocellularity in all groups using dexamethasone. Marrow iron staining was performed and ruled out any iron deficiency in all groups. These results suggest that glucocorticoids modulate erythropoisis in two ways depending on concentrations, enhancing erythropoiesis greatly at loading dosage while suppressing it at lower maintenance doses. Our data, together with our clinical observations, present an interesting phenomenon of cross modulation of the two widely used medications, Epo and glucocorticoids. It certainly warrants further investigation of involving pathways at molecular levels. In Vivo Effects of Dexamethasone on Epo stimulated erythropoiesis In Vivo Effects of Dexamethasone on Epo stimulated erythropoiesis

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