I. ANTI-ANDROGENIC EFFECTS OF A NEW STEROID TSAA-291 (16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE) AND ITS DERIVATIVES

1979 ◽  
Vol 92 (3_Supplb) ◽  
pp. S2-S23 ◽  
Author(s):  
Ryo Nakayama ◽  
Michio Masuoka ◽  
Tsuneo Masaki ◽  
Kiro Shimamoto

ABSTRACT Anti-androgenic properties of newly synthesized steroidal compounds, TSAA-291* and its derivatives, were studied in the rat. (1) Subcutaneous administrations of TSAA-291 and TSAA-272* were effective in depressing the weight of seminal vesicles and ventral and dorsal prostates in the adult rat. (2) TSAA-291, TSAA-328* and TSAA-272 were shown to be anti-androgenic by the subcutaneous or oral route in the immature castrated male rat treated with testosterone propionate. The dose-response curves of all the test agents expressed in terms of percentage inhibition were approximately parallel to each other. Cyproterone acetate depressed the weight of levator ani muscle dose-dependently, whereas TSAA-291, TSAA-328 and TSAA-330* did not inhibit the muscle weight in a dose range sufficiently effective in inhibiting the weight of seminal vesicles and ventral and dorsal prostates. (3) TSAA-291 was also antiandrogenic against androstenedione and dehydroepiandrosterone. (4) Local administration of the anti-androgenic compounds into the left seminal vesicle or left testis of the young adult rat depressed the weight of the seminal vesicle or testis on the treated side as compared with the vehicle-injected contra-lateral side.

Author(s):  
V. F. Allison ◽  
G. C. Fink ◽  
G. W. Cearley

It is well known that epithelial hyperplasia (benign hypertrophy) is common in the aging prostate of dogs and man. In contrast, little evidence is available for abnormal epithelial cell growth in seminal vesicles of aging animals. Recently, enlarged seminal vesicles were reported in senescent mice, however, that enlargement resulted from increased storage of secretion in the lumen and occurred concomitant to epithelial hypoplasia in that species.The present study is concerned with electron microscopic observations of changes occurring in the pseudostratified epithelium of the seminal vescles of aging rats. Special attention is given to certain non-epithelial cells which have entered the epithelial layer.


Genetics ◽  
2001 ◽  
Vol 158 (1) ◽  
pp. 333-340 ◽  
Author(s):  
Isabelle Le Roy ◽  
Sylvie Tordjman ◽  
Danièle Migliore-Samour ◽  
Hervé Degrelle ◽  
Pierre L Roubertoux

Abstract Comparisons across 13 inbred strains of laboratory mice for reproductive organ (paired seminal vesicles and paired testes) weights indicated a very marked contrast between the C57BL/6By and NZB/BINJ mice. Subsequently these strains were selected to perform a quantitative genetic analysis and full genome scan for seminal vesicle and testis weights. An F2 population was generated. The quantitative genetic analyses indicated that each was linked to several genes. Sixty-six short sequences for length polymorphism were used as markers in the wide genome scan strategy. For weight of paired testes, heritability was 82.3% of the total variance and five QTL contributed to 72.8% of the total variance. Three reached a highly significant threshold (>4.5) and were mapped on chromosome X (LOD score 9.11), chromosome 4 (LOD score 5.96), chromosome 10 (LOD score 5.81); two QTL were suggested: chromosome 13 (LOD score 3.10) and chromosome 18 (LOD score 2.80). Heritability for weight of seminal vesicles was 50.7%. One QTL was mapped on chromosome 4 (LOD score 9.21) and contributed to 24.2% of the total variance. The distance of this QTL to the centromere encompassed the distance of the QTL linked with testicular weight on chromosome 4, suggesting common genetic mechanisms as expected from correlations in the F2. Both testis and seminal vesicle weights were associated with a reduction in the NZB/BINJ when this strain carried the YNPAR from CBA/H whereas the YNPAR from NZB/BINJ in the CBA/H strain did not modify reproductive organ weights, indicating that the YNPAR interacts with the non-YNPAR genes. The effects generated by this chromosomal region were significant but small in size.


2001 ◽  
Vol 125 (1) ◽  
pp. 141-145
Author(s):  
Rajal B. Shah ◽  
Min W. Lee ◽  
Alvaro A. Giraldo ◽  
Mahul B. Amin

Abstract Context.—We have observed intraluminal crystalloid morphology in seminal vesicles that is superficially similar to that seen in prostate neoplasia, but found little information on such morphology in the literature. Design.—Two hundred fifty-three prostate specimens (163 needle biopsies, 75 radical prostatectomies with prostate carcinoma, 11 prostates from autopsy, and 4 cystoprostatectomies without prostate carcinoma) were examined for seminal vesicle secretions, which were categorized as (a) dense platelike inspissated, (b) fluidlike, (c) crystalloid morphology, and (d) absent. Histochemical stains (periodic acid–Schiff with and without diastase, Alcian blue at pH 2.5, and mucicarmine) were performed to characterize the nature of secretions. Results.—Proteinaceous secretions were identified in 82% of seminal vesicles examined. Of these, 61% had predominantly dense, platelike, inspissated secretions, 15% had predominantly fluidlike secretions, and 24% had predominantly crystalloid morphology. Although in some cases the crystalloid morphology resembled that of prostatic intraluminal crystalloids, the seminal vesicle crystalloids differed in that they were invariably multiple, had curved edges, and had varied forms (elliptical, cylindrical, rodlike, and rectangular). Seventy-one percent of seminal vesicle crystalloids were associated with dense, platelike, inspissated secretions and appeared to be created by fracturing within platelike secretions. There was no relationship between seminal vesicle crystalloid morphology and associated malignancy in the prostate gland, as it was seen in 24% of cases with prostate carcinoma and 25% of cases without prostate carcinoma (P = 1.0000). Fluidlike secretions were positive for Alcian blue (pH 2.5) and mucicarmine, whereas dense platelike secretions and crystalloid morphology were negative for Alcian blue (pH 2.5) and mucicarmine. Conclusions.—Seminal vesicle secretions are fairly common and, when fluidlike, are composed of acid mucopolysaccharides. Inspissation of secretions appears to be associated with loss of acidity, presumably resulting in dense platelike secretions and crystallization. Awareness of both the crystalloid morphology in seminal vesicle tissue and the distinguishing features from prostatic crystalloids may be important while interpreting prostate needle biopsies in which seminal vesicle epithelium may be confused for prostate carcinoma because of a small acinar morphology with accompanying cytologic atypia and crystalloid morphology.


1978 ◽  
Vol 235 (4) ◽  
pp. E422 ◽  
Author(s):  
L A Bruce ◽  
F M Behsudi ◽  
I E Danhof

Male Sprague-Dawley rats were pretreated subcutaneously with either progesterone (3 mg/kg per day) in a vehicle or a vehicle only for 3 days. Antral and gastroduodenal junctional tissues (GJT) were excised from both groups of animals and prepared for in vitro mechanical measurements. Responses from the circular muscle axis of these tissues were recorded with strain gauge transducers over a 30-min period. Chemical stimulation of the tissue was achieved with a muscarinic agonist, bethanechol chloride. Log-dose response curves suggested that untreated antral tissue generated stronger contractile activity than untreated GJT on an equal weight basis at bethanechol dose levels of 6.4 X 10(-6) M to 1 X 10(-4) M (P less than 0.005). Antral tissue and GJT contractile activity from the progesterone pretreated animals was significantly reduced (P less than 0.01) compared to the corresponding tissues from untreated animals at bethanechol dose levels of 6.4 X 10(-6) M and 1.28 X 10(-5) M. Progesterone pretreatment appeared to have little effect on the contractile frequency of either tissue. These results suggest possible progesteronic influences on contractile force in gastrointestinal smooth muscle.


Author(s):  
Haka As'ada ◽  
Yardi Saibi ◽  
Hendri Aldrat

Ashitaba leaves (Angelica keiskei) or also known as tommorow's leaf is plant that known to have various health benefit, one of them is as an anti-inflammatory activity. The anti-inflammatory activity of ashitaba leaves has been known through in vitro assays. This study aims to determine the anti-inflammatory activity of 70% ethanol extract of ashitaba leaves through in vivo assay. Anti-inflammatory activity was performed on white male rat of Sprague dawley strain with induction method of edema on rat's foot using 1% carrageenan 0.2 ml. Rats were divided into 5 groups. The negative control group was given a 0.5% Na-CMC suspension, a positive control group was given sodium diclofenac suspension of 5.14 mg / kgBW, and the test group was given 70% ethanol extract of ashitaba leaves at a dose of 1000; 2000; and 4000 mg / kgBW suspended in 0.5% Na-CMC. The results showed that in that dose range the 70% ethanol extract of ashitaba leaves had anti-inflammatory activity that did not depend on the dose. Percentage of edema of 70% ethanol extract of ashitaba leaves dose 1000; 2000; 4000 mg / kgBB was significantly different with negative control (p ≤ 0,05) and had percentage of edema inhibition respectively 83,95%, 79,01%, and 80,25%. The results of this study showed that 70% ethanol extract of ashitaba leaves have anti-inflammatory activity. Keywords: Ashitaba, Angelica keiskei, tommorow's leaf, anti-inflammatory, carrageenan.


2008 ◽  
Vol 22 (11) ◽  
pp. 2448-2465 ◽  
Author(s):  
Ramesh Narayanan ◽  
Christopher C. Coss ◽  
Muralimohan Yepuru ◽  
Jeffrey D. Kearbey ◽  
Duane D. Miller ◽  
...  

Abstract Androgen receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their pharmacological effects.


Development ◽  
1989 ◽  
Vol 106 (2) ◽  
pp. 219-234 ◽  
Author(s):  
S.J. Higgins ◽  
P. Young ◽  
J.R. Brody ◽  
G.R. Cunha

Functional cytodifferentiation of seminal vesicle epithelium was investigated in tissue recombinants. Neonatal rat and mouse seminal vesicles were separated into epithelium and mesenchyme using trypsin. Epithelium and mesenchyme were then recombined in vitro to form interspecific rat/mouse homotypic recombinants. Growth as renal grafts in adult male athymic mice resulted in seminal vesicle morphogenesis in 70% of the recombinants (the remaining 30% failed to grow). Functional cytodifferentiation was judged by the expression of the major androgen-dependent secretory proteins characteristic of the seminal vesicles of adult rats and mice. Antibodies specific for each of these proteins were used to screen tissue sections by immunocytochemistry and to probe protein extracts by immunoblotting techniques. The heterospecific recombinants synthesized the full range of seminal vesicle secretory proteins that typifies the species providing the epithelium of the recombinant, not the mesenchyme. There was little functional variation between individual recombinants. The time course of development corresponded to that of intact neonatal seminal vesicles grown under the same conditions. Morphogenesis and functional cytodifferentiation were not evident after one week, but were well advanced after two weeks. Seminal vesicle recombinants grown for three weeks were indistinguishable morphologically and functionally from normal adult seminal vesicles. In addition, the ability of adult seminal vesicle epithelium to be induced to proliferate was examined. In association with neonatal seminal vesicle mesenchyme, the epithelium of the adult seminal vesicle proliferated and retained its normal functional activity. Thus, seminal vesicle functional cytodifferentiation can be faithfully reproduced in homotypic tissue recombinants. The methods used in this study will be used to investigate seminal vesicle development in instructive inductions of heterotypic epithelia.


Development ◽  
1989 ◽  
Vol 106 (2) ◽  
pp. 235-250 ◽  
Author(s):  
S.J. Higgins ◽  
P. Young ◽  
G.R. Cunha

When grown as renal grafts in adult male hosts, the upper (cranial), middle and lower (caudal) portions of fetal mouse and rat Wolffian ducts developed into epididymis, epididymis plus ductus deferens, and seminal vesicle, respectively. In heterotypic tissue recombinants, the epithelia from upper and middle Wolffian ducts were instructively induced to undergo seminal vesicle morphogenesis by neonatal seminal vesicle mesenchyme. Functional cytodifferentiation was examined in these recombinants using antibodies against major androgen-dependent, seminal vesicle-specific secretory proteins. The instructively induced Wolffian duct epithelia synthesized normal amounts of all of the secretory proteins characteristic of mature seminal vesicles, as judged by immunocytochemistry on tissue sections and gel electrophoresis plus immunoblotting of secretions extracted from the recombinants. In heterospecific recombinants composed of rat and mouse tissues, the seminal vesicle proteins induced were specific for the species that had provided the epithelium. This showed that the seminal vesicle epithelium in the recombinants was derived from instructively induced Wolffian duct epithelium and not from epithelial contamination of the mesenchymal inductor. Upper Wolffian duct epithelium, instructively induced to undergo seminal vesicle morphogenesis, did not express epididymis-specific secretory proteins, showing that its normal development had been simultaneously repressed.


Author(s):  
J Daniel ◽  
R Sevy ◽  
L Salganicoff

Previous experiments have established that a 20,000 daltons protein which becomes phosphorylated when platelets are stimulated by thrombin is a myosin light chain. A model of thrombin activated platelets, in which the tension generated by contraction of the platelet aggregate is measured under isometric conditions, was used to study the relationships between steady-state myosin light chain phosphorylation and tension generation. After thrombin activation the platelet aggregate contracted, and in the contracted state myosin light chain was found to be phosphorylated. Relaxation induced by either PGI2 (which activates adenyl cyclase) or 120 mM K2SO4 containing 2 mM EGTA (which is presumed to deplete cytoplasmic Ca++) was accompanied by dephosphorylation of myosin light chain. Recontraction of the relaxed preparation with either ADP (10-4M) or epinephrine (10-6M) in the presence of Ca++ was accompanied by rephosphorylation of myosin light chain. The relationships between isometric tension, cAMP production and myosin light chain phosphorylation and dephosphorylation were studied in the contracted thrombin activated preparation subsequently relaxed with graded doses of PGI2(3×10-9 to 3×10-6M), such that complete dose-response curves were obtained. There was a striking positive correlation between the level of isometric tension and the degree of phosphorylation of myosin light chain. Over the same dose range of PGI2 there was no increase in cAMP levels, within the error of the detection procedure, until the ED- 50 (approx. 3×10-8M) for relaxation with PGI2 was exceeded. At the same time that relaxation and myosin light chain dephosphorylation occurred in response to PGI2 there was phosphorylation of a 22,000 daltons band; relaxation with K2SO4-EGTA did not affect this band. The above experiments are consistent with the hypothesis that myosin light chain phosphorylation is directly involved in platelet contraction.


2000 ◽  
pp. 406-410 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
J Navarro ◽  
C Dieguez ◽  
...  

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the biological actions of leptin in different experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a continuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis in vitro. In addition, a comparison of the effects of human recombinant leptin and leptin(116-130) amide at the pituitary level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7)M) significantly inhibited both basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion in vitro. Similarly, incubation of testicular tissue in the presence of increasing concentrations of leptin(116-130) amide (10(-9)-10(-5)M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7)M upwards. In addition, leptin(116-130) amide, at all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of leptin, acting at the testicular level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. In addition, we provide evidence for a direct inhibitory action of leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native leptin molecule, in the adult male rat.


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