Rabbit Prostate Research Articles

The estrogen receptor expression in the male rabbit urethra and prostate following castration.

The influence of castration on estrogen receptor (ER) expression in the male rabbit prostate and urethra, was investigated immunohistochemically and biochemically in 18 mature male, rabbits 14 days after bilateral orchiectomy, and in 15 controls. Immunohistochemical scores of ER were increased significantly in the prostatic stroma and the urethral submucosa (p < 0.05 Mann-Whitney), while the increase in the urothelium was not significant. Biochemically, the ER content was 87.4 +/- 42.6 f mol/mg protein in the normal prostate, and 190.0 +/- 28.0 f mol/mg protein following castration. The corresponding values for the posterior urethra were 228.3 +/- 43.2 f mol/mg protein and 354.9 +/- 60.1 f mol/mg protein. In both cases the increase was not significant. We conclude, that ERs in the prostate and the urethra of the male rabbit can be modified by hormonal manipulation. ERs may therefore be functionally active and not rudimentary.

Expression of prostatic TRH-like peptides differs between species and between malignant and nonmalignant tissues.

Thyrotropin-releasing hormone-immunoreactive peptides (iTRH) were analyzed in normal rat and rabbit prostates and in human benign prostatic hyperplasia (BPH) and prostate cancer. Peptides were extracted from tissues, fractionated by anion and cation exchange chromatography, and analyzed by TRH radioimmunoassay. pGlu-Glu-Pro-NH2 predominated in rabbit, but accounted for only 10-15% of iTRH in rat and human BPH. Uncharged peptides predominated in rat and human prostate. Authentic TRH (pGlu-His-Pro-NH2) is not present in rabbit prostate, but may account for up to 25% of iTRH in rat and human prostate. iTRH was virtually absent in prostate cancer. These results demonstrate considerable heterogeneity in the expression of TRH-like peptides in the prostates of various animal species, and suggest decreased expression of these peptides in prostate cancer.

Subtypes of α1-adrenoceptors in prostatic urethra and prostate of rats, rabbits and dogs

Subtypes of α1-adrenoceptors in prostatic urethra and prostate of rats, rabbits and dogs

Orchiectomy upregulates rabbit prostate peripheral benzodiazepine receptors

The effect of orchiectomy on peripheral benzodiazepine receptors (PBZr) in the rabbit prostate was studied. The mean PBZr density in the mitochondrial fraction isolated from prostates of intact (non castrated) rabbits was 4066 fmol/mg protein which following castration increased to 7236 fmol/mg protein ( p<0.005). The apparent dissociation constant (K D) of prostatic PBZr was higher in castrated rabbits (4.2 nM) than in intact animals (2.7 nM). These data suggest a role of androgen in the regulation of prostatic PBZr.

O-359 - Specific IK29 (novel α1-adrenoceptor antagonist) binding site in rabbit prostate and aorta

O-359 - Specific IK29 (novel α1-adrenoceptor antagonist) binding site in rabbit prostate and aorta

TRH-related peptides in the rabbit prostate complex during development

The novel peptide, pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2), has recently been isolated and characterized from the rabbit prostate complex. The tripeptide is present in high concentrations in the prostate complex and semen, together with a 40-50 residue polypeptide which contains a TRH-immunoreactive fragment at its C-terminus. The present study investigates changes in the levels of these TRH-related peptides in rabbits aged 11 weeks, 4 months, 7 months, 13 months and 2 years. For each age group the peptides were extracted from the prostate complex, separated by gel exclusion chromatography, and located by TRH radioimmunoassay. The TRH-immunoreactive fragment was released from the polypeptide by trypsin digestion prior to radioimmunoassay. Very low concentrations of TRH-immunoreactive peptides were present at 11 weeks of age, but considerable levels of both peptides were found in all the other age groups. Anion exchange chromatography, under conditions which resolve TRH and pGlu-Glu-ProNH2, showed that the majority of the low molecular weight TRH immunoreactivity co-eluted with synthetic pGlu-Glu-ProNH2. The remaining TRH immunoreactivity, which had not bound to the anion resin, also failed to bind to a cation exchange column at pH 2.0, indicating that it was not authentic TRH. Dissection of the prostate complex into its four constitutive regions (vesicular gland, coagulating gland, prostate and bulbourethral gland) followed by extraction, chromatography and TRH radioimmunoassay of each region showed that the TRH-related peptides were located in the prostate.

The TRH-like peptide pGlu-Glu-ProNH 2 is present in the porcine pituitary but not in reproductive tissues

The peptide pGlu-Glu-ProNH 2, which differs from thyrotrophin-releasing hormone (TRH) by only one amino acid, was initially detected and characterised in the rabbit prostate complex and more recently in human semen and rat pituitary. A previous study reported that TRH and a homologous peptide were present in a range of porcine tissues and it was of interest to further characterise these peptides. In this study, high levels of TRH-immunoreactivity have been demonstrated in the porcine pituitary, the majority of which was authentic TRH; although 9% was found to be chromatographically identical to pGlu-Glu-ProNH 2. In contrast, TRH-immunoreactivity was not detected in follicular fluid, ovary or prostate. The unexpected finding that pGlu-Glu-ProNH 2 is present in the porcine pituitary but absent from regions of the reproductive tract may be of biological significance.

Partial characterisation of a TRH-immunoreactive peptide from rabbit prostate

Partial characterisation of a TRH-immunoreactive peptide from rabbit prostate

PYROGLUTAMYLGLUTAMYLPROLINEAMIDE IS PRESENT IN RAT ANTERIOR AND POSTERIOR PITUITARY GLAND

A new TRH-like peptide pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2) has recently been purified and characterized from both the rabbit prostate complex and human semen. In this study, TRH-immunoreactive peptides were extracted from anterior pituitary, posterior pituitary and hypothalamus and subjected to gel exclusion chromatography. For each tissue, TRH was resolved from pGlu-Glu-ProNH2 by anion-exchange chromatography at pH 7.6. In the anterior pituitary, 63% of the TRH immunoreactivity was chromatographically identical to pGlu-Glu-ProNH2 whereas in the posterior pituitary the new peptide represented less than 5% of the total TRH immunoreactivity. Only trace levels of pGlu-Glu-ProNH2 were observed in hypothalamus, suggesting that the acidic TRH-related peptide found in the anterior pituitary may not be of hypothalamic origin. The new TRH-like peptide was purified from whole pituitaries by gel exclusion and ion-exchange chromatography, followed by high power liguid chromatography and was shown to have chromatographic properties identical to pGlu-Glu-ProNH2. Amino acid analysis of the purified peptide revealed glutamic acid and proline residues in the ratio Glx:2 Pro:1, which is the expected composition of pGlu-Glu-ProNH2 after acid hydrolysis.

Computer assisted anatomical reconstruction: a prostate model

We report a computer assisted three dimensional reconstruction technique using serial sections. This reconstruction was achieved by means of a common microcomputer. The organ analyzed in this study was the common European rabbit prostate.

家兎前立腺自律神経受容体に及ぼす加齢の影響

The amount of autonomic receptors in the old and young rabbit prostate homogenate was measured in order to study the effect of age on the autonomic receptors of the prostate using radioligand binding techniques. For measuring the adrenergic alpha-1, alpha-2, beta-receptors and cholinergic muscarinic receptors, 3H-Prazosin (3H-PZ), 3H-Yohimbine (3H-YOH), 3H-Quinuclidinylbenzilate (3H-QNB) were used, respectively. It was found that both the young and old rabbit prostate has a single class of binding sites for each ligand examined. There was an age-related difference in the distribution of these autonomic receptors (young: alpha 1 = muscarinic greater than alpha 2 greater than beta, old: alpha 1 greater than muscarinic greater than alpha 2 greater than beta). There were more alpha-1 and alpha-2 receptors in the old rabbit prostate, although these differences were not statistically significant. There was no age-related differences in the amount of beta adrenergic and muscarinic receptors. These results demonstrate that the age may affect the distribution of autonomic receptors but not significantly the amount of autonomic receptors of rabbit prostate.

Electrical and mechanical activity of rabbit prostate smooth muscles in response to nerve stimulation.

1. The rabbit prostate contains two smooth muscle bundles: one forms the capsule of the prostate and the other runs longitudinally in the outermost layer of the prostate. The former was contracted by exogenously applied noradrenaline (NA) and the latter by acetylcholine (ACh), and were therefore identified as NA-sensitive and ACh-sensitive muscles, respectively. 2. In the NA-sensitive muscle, exogenously applied NA, but not ACh, depolarized the smooth muscle membrane, and this action of NA was antagonized by prazosin but not by yohimbine. The membrane of the ACh-sensitive muscle was depolarized by ACh and hyperpolarized by NA. The former was antagonized by atropine and the latter by phentolamine. 3. In both bundles, electrical stimulation of intramural nerves elicited a biphasic junction potential: an excitatory junction potential (EJP) followed by an inhibitory junction potential (IJP). In the NA-sensitive muscle, the EJP was resistant to alpha-adrenoreceptor antagonists and sensitive to guanethidine, while the IJP was sensitive to apamin and resistant to alpha- or beta-adrenoreceptor antagonists or guanethidine. The EJP and IJP elicited in the ACh-sensitive muscle were inhibited by atropine and apamin, respectively, but both potentials were resistant to alpha- or beta-adrenoreceptor antagonists or guanethidine. 4. Transmural nerve stimulation elicited a twitch contraction in both muscle bundles, and the contractions in the NA-sensitive muscle were partially inhibited by prazosin and blocked completely by guanethidine. The contraction of the ACh-sensitive muscle was blocked by atropine. Contractions produced by exogenously applied NA and ACh were antagonized by prazosin and atropine, respectively. 5. It is concluded that in the rabbit prostate there are two smooth muscles bundles which are respectively contracted with associated depolarization by NA or ACh. The NA-sensitive muscle receives adrenergic excitatory and non-adrenergic non-cholinergic inhibitory innervation. The ACh-sensitive muscle receives cholinergic excitatory and non-adrenergic non-cholinergic inhibitory innervation.

The TRH-related peptide pyroglutamylglutamylprolinamide is present in human semen

We have recently identified a novel peptide in the rabbit prostate complex which cross-reacts with an antibody to thyrotrophin-releasing hormone (TRH) and has the structure pGlu-Glu-ProNH 2. In the present study, high concentrations of a TRH-related tripeptide and also a polypeptide (10–12 kDa) containing a TRH-immunoreactive peptide at its C-terminus were detected in human semen. The low molecular mass TRH-like peptide and the immunoreactive fragment from the polypeptide were isolated from human semen and shown to have identical structures. Amino acid analysis suggested compositions Glx 2, Pro 1, and after mild acid hydrolysis, the same sequence, Glu-Glu-Pro, was established for the two peptides. Fast atom bombardment (FAB) mass spectrometry yielded a pseudomolecular ion (M + H) + of 355.38 which was identical to that of the synthetic peptide pGlu-Glu-ProNH 2. The data demonstrate that human semen contains the TRH-like peptide pyroglutamylglutamylprolinamide and also a polypeptide terminating in the sequence Gln-Glu-ProNH 2.

A novel peptide, pyroglutamylglutamylproline amide, in the rabbit prostate complex, structurally related to thyrotrophin-releasing hormone

A novel peptide which cross-reacts with an antibody to thyrotrophin-releasing hormone has been isolated and characterized from the rabbit prostate complex. The peptide exhibited an amino acid composition of Glx1.7, Pro1.0, and automatic gas phase sequence analysis after mild acid hydrolysis established the sequence Glu-Glu-Pro. Fast atom bombardment mass spectrometry gave a pseudomolecular ion (M + H)+ of 355.2 confirming that the prostate peptide has the structure of pGlu-Glu-Pro-NH2. This peptide differs from authentic thyrotrophin-releasing hormone by the substitution of glutamic acid for histidine at position 2.

Thyrotrophin-releasing hormone-related polypeptides in rabbit prostate and semen are different from those in rabbit hypothalamus

TRH-related peptides were extracted from the hypothalamus and prostate gland of the rabbit. The peptides were fractionated by gel exclusion chromatography and located by trypsin digestion and radioimmunoassay with antibodies to TRH amide and TRH-Gly Lys. In the hypothalamus TRH-related peptides containing approximately 16 and 30 residues were observed: in these peptides the extensions to the TRH sequence were exclusively in the C-terminal direction. In addition, the three-residue form of TRH was also present. In the prostate complex, the predominant TRH-related peptide contained approximately 50 residues and the extension to the TRH tripeptide was on the N-terminal side; a three-residue form of immunoreactive TRH was also demonstrated. The same pattern of TRH-related peptides was shown to be present in rabbit semen. The results reveal the existence of a novel TRH-related polypeptide in the prostate and semen which does not occur in the hypothalamus. This peptide appears to undergo secretion.

Electrical and mechanical properties of the capsular smooth muscles of the rabbit prostate in relation to the actions of the alpha 1-adrenoceptor blocker, YM-12617.

1. Electrical and mechanical properties of smooth muscle cells of the rabbit prostate capsule and the actions of the alpha 1-adrenoceptor blocker, YM-12617, were investigated using microelectrode and isometric tension recording methods. 2. The capsular muscles comprised thick and thin muscle bundles. In the former, noradrenaline (NA; 0.1-10 microM) provoked the phasic and tonic mechanical responses, with twitch contractions superimposed on the tonic response. YM-12617, in concentrations over 1 nM inhibited the contraction evoked by any given concentration of NA. Yohimbine (up to 10 microM) slightly inhibited the NA-induced contraction whilst clonidine (up to 10 microM) and acetylcholine (ACh; up to 10 microM) produced no mechanical response. 3. In thin muscle bundles, NA (0.1-10 microM) produced a contraction but the phasic response was small and the tonic response was negligible. These changes were blocked by YM-12617. In contrast, ACh (0.1-10 microM) produced atropine-sensitive, large phasic and tonic responses similar to those observed on application of NA to thick muscle bundles. 4. In thin and thick muscle bundles, the mean resting membrane potentials were -54 and -56 mV, respectively, values which were not statistically different. However, in thick muscle bundles, NA (over 0.1 microM) depolarized the membrane in a concentration-dependent manner and produced repetitive spike generation; ACh (up to 1 microM) did not modify the membrane potential. In thin muscle bundles, the above concentrations of NA hyperpolarized the membrane but ACh produced a large depolarization with repetitive spike generation. 5. In thick muscle bundles, nifedipine (0.3 microM) blocked twitch contractions generated spontaneously or provoked by application of NA with no effect on phasic and tonic responses. The NA-induced depolarization persisted after superfusion with nifedipine up to a concentration of 1.0 microM. In a Ca-free solution containing 2 mM EGTA, NA produced only the phasic responses, and re-addition of Ca (2.6 mM) restored the generation of a tonic response. 6. After application of 0.3 microM nifedipine, the effects of YM-12617 and prazosin were observed on the tonic component of the NA-induced contraction of thick muscle bundles. The ID50 values for YM-12617 and prazosin were 1 nM and 15 nM, respectively (n = 4). YM-12617 shifted the NA concentration-response curve to the right in a concentration-dependent and parallel manner. The Schild plot yielded a straight line with slope of 0.97 +/- 0.05, (n = 4). The pA2 value for YM-12617 was 10.4 +/- 0.05, (n = 4). 7. In thiqk muscle bundles, the depolarization induced by NA (1O microM) was blocked by YM-12617 (over 1 nM) to a greater extent than by prazosin (0.1 microM). Half-inhibition of the NA (10 microM)-induced maximum depolarization by YM-12617 or prazosin occurred at concentrations of 2 nm and 100 nM, respectively. 8. From these mechanical and electrical responses, the heterogeneous nature and distribution of alpha-adrenoceptors and muscarinic receptors has been elucidated in capsular smooth muscles in the rabbit prostate. In both thick and thin muscle bundles, NA-induced electrical and mechanical responses were more potently inhibited by YM-12617 than by prazosin.

Alpha 1-Adrenoceptor subtype mediating contraction of the smooth muscle in the lower urinary tract and prostate of rabbits.

The alpha-adrenoceptor subtype mediating contraction of the smooth muscle in the urinary bladder base (trigone), proximal urethra and prostate isolated from male rabbits was investigated by comparing the responsiveness to alpha-adrenoceptor agonists and antagonists under condition where beta-adrenoceptors and neuronal and extraneuronal uptakes were inhibited. Noradrenaline (non-selective), phenylephrine (alpha 1-selective) and clonidine (alpha 2-selective) caused a dose-dependent contraction in the trigone, urethra and prostate. Phenylephrine acted as a full agonist whereas clonidine was a partial agonist. YM-12617 and prazosin (alpha 1-selective), phentolamine (non-selective) and yohimbine (alpha 2-selective) produced dose-dependent shifts to the right of the dose-response curves for noradrenaline, phenylephrine and clonidine in the all three tissues. YM-12617 (pA2 = 9.77, 9.67 and 9.73 for trigone, urethra and prostate, respectively), prazosin (pA2 = 8.26, 8.20 and 8.08), phentolamine (pA2 = 7.67, 7.62 and 7.45) and yohimbine (pA2 = 6.30, 6.30 and 5.94) showed constant pA2 values irrespective of the agonists and tissues used, suggesting that only a single subclass of alpha-adrenoceptors is present. The actual pA2 values for these antagonists are comparable to those reported previously in tissues said to contain mainly alpha 1-adrenoceptors. Thus, we concluded that the postsynaptic alpha-adrenoceptors of the rabbit trigone, urethra and prostate mediating contraction belong to the alpha 1-subtype.

P-193) - α1-Adrenoceptor subtype mediating contraction in the urethra and prostate of rabbits

P-193) - α1-Adrenoceptor subtype mediating contraction in the urethra and prostate of rabbits

The effects of estradiol, tamoxifen, and testosterone on the weights and histology of the epididymis and accessory sex organs of sexually immature rabbits.

The effects of estradiol benzoate (EB), testosterone propionate (TP), and Tamoxifen, alone or in combination, on the weight and morphology of the male accessory sex glands were studied in intact and in castrated immature rabbits. TP treatments (2 mg/kg) exerted a stimulatory effect on the glands, resulting in a significant increase in the weight of the epididymis, the proprostate, and the prostate of castrated rabbits, and of the bulbourethral glands of both intact and castrated rabbits, and in marked morphological changes in all the glands. the epithelium was stimulated but retained its pseudostratified columnar appearance and resembled more the epithelium of normal mature males than that of age matched controls. The bulbourethral glands were the most responsive and the vesicular gland the least responsive to androgen treatment. The response of the glands to EB (25 micrograms/kg) was characterized by significant weight increases in all the glands of both castrated and intact rabbits, hypertrophy of the musculo-fibrous components and proliferation of the basal layer of the epithelium leading to squamous metaplasia and leukocytic infiltration. Hyperplasia of the fibromuscular stroma was most evident in the cauda epididymidis and in the vesicular gland. Squamous metaplasia and leukocytic infiltration were most evident in the ejaculatory duct and in the structures adjacent to it. The antiestrogen, Tamoxifen (250 micrograms/kg), and TP (2 mg/kg) given in conjunction with EB (25 micrograms/kg) tended to reduce the weight increase caused by estrogen, but the decrease was significant in only a few instances. Tamoxifen (250 micrograms/kg) administered alone stimulated the epithelium of the accessory sex glands and induced squamous metaplasia, but did not induce hyperplasia of the fibromuscular stroma. The study demonstrates that accessory sex glands display a consistent pattern of differential sensitivity to both androgens and estrogens and that these hormones exert their action on different cell types within the organ.

Normal tissue response to localized deep microwave hyperthermia in the rabbit's prostate: A preclinical study

Experiments were performed to determine the response of normal tissues of the rectal cavity and the prostate to localized 2.45 GHz microwave deep hyperthermia. Hyperthermia at 43°C was delivered by means of a coaxial probe in the rectal cavity for 30 min. once or twice at an interval of 2 days. Normal tissues of the rectum, urinary bladder, and prostate were histologically examined up to three months after treatments. In almost all of the treated animals no tissue and organ injury resulted from localized deep hyperthermia at 43°C. This treatment appears to be safe for the treatment of carcinoma of the prostate.