Effects of mepartricin on estradiol and testosterone serum levels and on prostatic estrogen, androgen and adrenergic receptor concentrations in adult rats

Badino, P.; Odore, R.; Vigo, D.; Bonabello, A.; Rabino, S.; Capello, F.; Bruzzese, T.

doi:10.1006/phrs.2001.0846

Cited by 9 publications

(15 citation statements)

References 29 publications

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“…This result is in agreement with that observed in previous experiments, in which a significant reduction of the prostate weight was observed in normal immature (Shakutou et al. , 1999) and adult rats (Re et al. , 2001b).…”

Section: Discussionsupporting

confidence: 94%

“…Therefore, if clinically effective, a nonsystemic nonhormonal treatment of dogs affected by BPH may be regarded favourably by both veterinarians and owners. The present experiment was conceived on the preliminary results of a previous study conducted in adult rats (Re et al. , 2001b) with the aim of determining the effects induced by oral administration of mepartricin on hormone serum concentrations and oestrogen receptor (ER), AnR, and AR subtype concentrations in the prostate of aged rats.…”

Section: Introductionmentioning

confidence: 99%

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Mepartricin long‐term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats

Barbero

Badino

Odore

et al. 2006

Vet Pharm & Therapeutics

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Mepartricin is a semi-synthetic macrolide antibiotic developed as a drug for the treatment of benign prostatic hyperplasia (BPH) in human patients. In the present study, aged rats are used as an experimental model to evaluate the effects of mepartricin on circulating hormone concentrations and prostate receptor concentrations, to compare these possible effects with clinical findings observed in long-term treated dogs. Fifty-six aged male rats were randomly divided into four experimental groups treated orally with 0 (group 1), 2 mg (group 2), 5 mg (group 3) and 20 mg (group 4) mepartricin/kg of body weight. for 28 days respectively. Serum oestradiol and testosterone concentrations were measured by radio-immune-assays methods. Binding assays were used to measure the prostate concentrations of oestrogen receptors (ER), androgen receptors (AnR), alpha(1)-adrenergic receptor (alpha(1)-AR), and beta-adrenerergic receptor (beta-AR) subtypes. Mepartricin induced a significant reduction of prostate weight and serum oestradiol concentrations. Serum testosterone concentrations were unaffected. The treatment induced a significant down-regulation of ER concentrations (P < 0.05) and a significant up-regulation of AnR (P < 0.05) in rat prostate. Mepartricin induced a significant (P < 0.05) dose-dependent up-regulation of alpha(1)-AR and beta(2)-AR. In contrast, the concentration of beta(3)-ARs was significantly decreased (P < 0.05) in treated animals. The increase in prostate beta(2)-AR concentrations observed in subjects treated with mepartricin may be a favourable element in the evolution of BPH, because of the role exerted by these receptors in the control of prostatic smooth muscle relaxation. Curiously, beta(3)-AR concentrations were significantly reduced in treated animals. Data collected suggest that the prostatic beta-AR expression might be strongly influenced by oestrogen deprivation (mepartricin treatment); therefore, the combination of oestrogen suppression (mepartricin) and adrenergic suppression (alpha(1)-AR blockers) may be proposed as a possible nonhormonal therapeutic strategy for the treatment of benign prostatic hyperplasia in dogs.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Mepartricin long‐term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats

Barbero

Badino

Odore

et al. 2006

Vet Pharm & Therapeutics

Self Cite

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“…However, whether diethylstilbestrol has an androgenic effect remains uncertain. In our previous Hershberger assay, the weight of some male accessory sex organs increased in rats given the typical estrogenic compounds ethinyl estradiol, equilin, norgestrel, or estrone, but we could not determine whether these chemicals exhibit androgen agonistic properties (Yamasaki et al, 2003), because estrogen and androgen receptors are said to be present in the accessory sex organs of male rats and mice (Re et al, 2001;Weihua et al, 2001;Williams et al, 2001). On the other hand, the receptor binding affinity of other estrogenic compounds, i.e., 17␤-estradiol and tamoxifen, was higher than that of diethylstilbestrol, but no androgenic properties of these two estrogenic compounds were detected in the Hershberger assays.…”

Section: Discussionmentioning

confidence: 89%

Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals

et al. 2004

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“…It is worthy to note that serum levels of 17-␤-E in male adult rats range between 40 and 110 pmol/L. 33 In the male rat, most of this hormone is not testicular in origin but rather is derived from the adrenal glands. 34 These treatments provoked a significant increase in leukocyte-endothelial cell interactions 90 minutes after administration, which were Figure 7.…”

Section: Discussionmentioning

confidence: 99%

Estrogens Inhibit Angiotensin II–Induced Leukocyte–Endothelial Cell Interactions In Vivo via Rapid Endothelial Nitric Oxide Synthase and Cyclooxygenase Activation

Álvarez

Hermenegildo

Issekutz

et al. 2002

Circulation Research

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Abstract-Angiotensin II (Ang II) may be a key molecule in the development of atherosclerosis. Because the incidence of coronary atherosclerosis in premenopausal women is lower than that observed in men or postmenopausal women, we have investigated the effect of estrogens on Ang II-induced leukocyte recruitment in vivo using intravital microscopy in the rat mesenteric microcirculation. Superfusion for 60 minutes with Ang II induced a significant increase in leukocyte rolling flux, adhesion, and emigration. Administration of 17-␤-estradiol (17-␤-E) after 30 minutes of Ang II superfusion produced a reduction of these leukocyte responses by 55.1%, 72.7%, and 70.9%, respectively, an additional 30 minutes later. The effect observed with 17-␤-E was receptor-mediated and specific. 17-␤-E superfusion did not modify either L-NAME or indomethacin-induced leukocyte responses. Inhibitory responses caused by 17-␤-E were not altered by either 7-nitroindazole or actinomycin D cosuperfusion. Stimulation of endothelial cells with 17-␤-E caused a rapid and dose-dependent release of prostacyclin. Finally, tamoxifen or ICI 182,780 administration provoked a significant increase in leukocyte-endothelial cell interactions 90 minutes later, which were significantly attenuated by systemic preadministration with an Ang II AT 1 receptor antagonist. Tamoxifen-induced leukocyte responses were also reduced by systemic pretreatment with an anti-P-selectin mAb and an anti-CD18 mAb. Hence, the antiatherogenic effects of estrogens may be mediated by inhibition of Ang II-induced leukocyte recruitment through endothelial NO and prostacyclin release. Furthermore, scarcity of estrogens resulted in decreased levels of vasodilators and the exposure of the endothelium to the deleterious action of Ang II, which may explain the higher incidence of coronary atherosclerosis in men and postmenopausal women.

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Effects of mepartricin on estradiol and testosterone serum levels and on prostatic estrogen, androgen and adrenergic receptor concentrations in adult rats

Cited by 9 publications

References 29 publications

Mepartricin long‐term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats

Mepartricin long‐term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats

Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals

Estrogens Inhibit Angiotensin II–Induced Leukocyte–Endothelial Cell Interactions In Vivo via Rapid Endothelial Nitric Oxide Synthase and Cyclooxygenase Activation

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