The Experts below are selected from a list of 390 Experts worldwide ranked by ideXlab platform
Michael G Mawhinney - One of the best experts on this subject based on the ideXlab platform.
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androgen induced norepinephrine release from postganglionic neurons mediates Accessory Sex Organ smooth muscle proliferation
The Journal of Urology, 2002Co-Authors: Julie Kim, Dennis Cole, Anne Johnson, Virgilio Centenera, Emmanuel Schenkman, John P Durham, Albert J Azzaro, Michael G MawhinneyAbstract:Purpose: Guinea pig seminal vesicle smooth muscle displays an initial androgen dependent, proliferative response during early puberty, followed by progression to an androgen resistant, amitotic state in adults. We determined the role of norepinephrine in androgen dependent pubertal proliferation and in the subsequent terminal differentiation of adult seminal vesicle smooth muscle.Materials and Methods: Guinea pig seminal vesicle provided a suitable model since its unique anatomy allowed clean harvest of smooth muscle without epithelium. Norepinephrine release from postganglionic adrenergic nerve terminals in seminal vesicle smooth muscle was measured using several techniques. Prazosin sensitive electrical field stimulation of contractile responses qualitatively assessed norepinephrine release. Norepinephrine release was quantified directly in vitro from incubated seminal vesicle smooth muscle minces and indirectly ex vivo from intact tissue using the endogenous seminal vesicle smooth muscle concentration ...
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m calpain activation depletion is associated with androgen induced reduction of protein kinase c and proliferation of male Accessory Sex Organ smooth muscles cells
The Journal of Urology, 1997Co-Authors: Norman Gebrosky, Dennis Cole, John P Durham, Caroline Stetterneel, Michael G MawhinneyAbstract:ABSTRACTPurpose: In the guinea pig seminal vesicle smooth muscle (SVM), androgen-dependent proliferation and terminal differentiation appear to be coupled to protein kinase C (PKC). This is based on the observations that both the soluble (cytosolic) enzyme and the Triton X-100 solubilizable form of the particulate enzyme were reduced during proliferation but were androgen-resistant in the amitotic state of adults. The purpose of the present investigation was to determine if the reduction in PKC activity was linked to the translocation of the activated enzyme to acceptor sites in the Triton X-100 insoluble fraction of the cell or reflected enzyme depletion due to proteolysis by androgen-dependent activation of the u- and/or m-calpains.Materials and Methods: SVM was harvested from treated animals, homogenized and separated into soluble and particulate components. The particulate material was further fractionated into Triton X-100 soluble and insoluble fractions. PKC activity was determined in all fractions ...
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protein kinases and the androgen induced proliferation of Accessory Sex Organ smooth muscle
Biology of Reproduction, 1992Co-Authors: Angelo Mariotti, John P Durham, Michael G MawhinneyAbstract:The possible role of second messenger systems in androgen-dependent smooth muscle proliferation was investigated. Focusing on the hormone-sensitive guinea pig seminal vesicle, we analyzed changes in protein kinase C (PKC) and cAMP-dependent type I and II protein kinases during the androgen-dependent smooth muscle proliferation of puberty, as well as in the transition to the nonproliferative state of the adult. The androgenic sensitivity of the cAMP-dependent type I and II protein kinases and the cAMP-dependent phosphorylations of soluble muscle proteins did not correlate with the qualitative change in the androgenic sensitivity of the prepubertal vs. adult animals. In contrast to the cAMP-dependent protein kinases, regulation of the soluble and particulate forms of PKC corresponded to the androgen-induced smooth muscle proliferation. That is, in the seminal vesicle muscle of prepubertal castrated animals, androgen treatment reduced both the soluble and particulate forms of PKC during the increase in smooth muscle DNA synthesis, and in adult seminal vesicle smooth muscle, which was resistant to androgen-induced proliferation, both forms of the enzyme were resistant to androgenic stimulation. It is concluded that PKC may be a component of an autocrine mitogenic mechanism involved in the coupling and uncoupling of androgen-induced smooth muscle proliferation.
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of Accessory Sex Organ smooth muscle1
1992Co-Authors: Angelo Mariotfi, John P Durham, Michael G MawhinneyAbstract:The possible role of second messenger systems in androgen-dependent smooth muscle proliferation was investigated. Focusing on the hormone.sensitive guinea pig seminal vesicle, we analyzed changes in protein kinase C (PKC) and cAMP.dependent type I and 11 protein kinases during the androgen-dependent smooth muscle proliferation of puberty, as well as in the transition to the nonproliferative state of the adult. The androgemc sensitivity of the cAMP-dependent type I and II protein kinases and the cAMP-dependent phosphorylations of soluble muscle proteins did not correlate with the qualitative change in the androgenic sensitivity of the prepubertal vs. adult animals. In contrast to the cAMP-dependent protein kinases, regulation of the soluble and particulate forms of PKC corresponded to the androgen.induced smooth muscle proliferation. That is, in the seminal vesicle muscle of prepubertal castrated animals, androgen treatment reduced both the soluble and particulate forms of PKC during the increase in smooth muscle DNA synthesis, and in adult seminal vesicle smooth muscle, which was resistant to androgen-induced proliferation, both forms of the enzyme were resistant to androgenic stimulation. It is concluded that PKC may be a component of an autocrine mitogenic mechanism involved in the coupling and uncoupling of androgen-induced smooth muscle proliferation.
Richard E. Peterson - One of the best experts on this subject based on the ideXlab platform.
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effects of aryl hydrocarbon receptor null mutation and in utero and lactational 2 3 7 8 tetrachlorodibenzo p dioxin exposure on prostate and seminal vesicle development in c57bl 6 mice
Toxicological Sciences, 2002Co-Authors: Kinarm Ko, Robert W Moore, Ulla Simanainen, Terry D. Oberley, Richard E. PetersonAbstract:Experiments were conducted to determine the effects of aryl hydrocarbon receptor (AhR) null mutation and in utero and lac- tational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, alone and in combination, on prostate and seminal vesicle devel- opment in C57BL/6 mice. AhR heterozygous (Ahr /- ) mice were mated, and pregnant females were dosed orally on gestation day 13 with TCDD (5 g/kg) or vehicle. Pups underwent necropsy on postnatal days (PNDs) 35 and 90. Comparison of vehicle-exposed AhR knockout (AhRKO; Ahr -/- ) with wild-type (Ahr / ) pups revealed that the AhR is necessary for normal dorsolateral pros- tate, anterior prostate, and seminal vesicle development but ap- parently not for ventral prostate development. In wild-type mice, in utero and lactational TCDD exposure reduced ventral prostate weight by 79 - 87% and mRNA expression for its major androgen- dependent secretory protein (MP25) by 99%. Yet high levels of mRNA for a secretory protein normally produced primarily by the lateral prostate (PSP94) were expressed. These effects were pre- dominantly AhR dependent because TCDD had little if any effect in AhRKO mice. TCDD reduced dorsolateral prostate weight in wild-type but not AhRKO mice and had no significant effect on expression of mRNA for PSP94 or for probasin, a major androgen- dependent secretory protein. The PSP94 results suggest that TCDD may have caused a respecification of prostatic gene expres- sion. TCDD reduced anterior prostate weight by more than half, and expression of mRNA for its major androgen-dependent secre- tory protein (renin-1) was greatly reduced. These effects were AhR dependent. Seminal vesicle weight was reduced by TCDD in wild-type mice but was increased in AhRKO mice on PND 35 and decreased on PND 90 (relative weight only). Androgen receptor mRNA levels were not significantly altered in any prostate lobe, and all Organs appeared histologically normal in all groups. Serum testosterone concentrations were unchanged, and modest reduc- tions in serum 5-androstane-3,17-diol concentrations could not account for the effects on Sex Organs. Collectively, these results indicate that the AhR signaling pathway plays a role in normal Accessory Sex Organ development and that in utero and lactational TCDD exposure disrupts development of these Organs via spa-
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interactive effects of tcdd andp p dde on male reproductive tract development inin uteroand lactationally exposed rats
Toxicology and Applied Pharmacology, 1999Co-Authors: Kati I Loeffler, Richard E. PetersonAbstract:Abstract The developing male rat reproductive system is highly sensitive to low doses of TCDD and p,p′ -DDE (DDE), which exert antiandrogenic effects via different mechanisms. This study investigates the interactive effects of in utero and lactational exposure to a mixture of these compounds. Pregnant Holtzman rats received one of the following: vehicle on gestation day (GD) 14–18, 0.25 μg/kg TCDD on GD15, 100 mg/kg DDE on GD 14–18, or 0.25 μg/kg TCDD on GD15 and 100 mg/kg DDE on GD 14–18. Male offspring were euthanized on postnatal day (PND) 21 (weaning), PND 32 (prepuberty), PND 49 (puberty), and PND 63 (postpuberty). Coadministration of these doses of TCDD and DDE appeared to potentiate their individual actions on prostate weight on PND 21, while immunostaining for the prostatic androgen receptor exhibited patterns characteristic of the effects of both compounds individually. Cauda epididymal sperm number was reduced by each compound but was not further reduced by exposure to TCDD and DDE in combination. Anogenital distance, age at onset of puberty, daily sperm production, testicular and Accessory Sex Organ weight (nonprostate), and levels of prostatic androgen-regulated gene transcripts are affected at higher doses of both compounds, but not at the doses used in the present study. Only DDE-treated animals retained nipples on PND 13. Serum androgen levels did not differ between treatment groups. In conclusion, the developing rat prostate is uniquely sensitive to the effects of TCDD and DDE, which may augment one another's effects in this Organ.
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in uteroand lactational exposure to 2 3 7 8 tetrachlorodibenzo ρ dioxin effects on development of the male and female reproductive system of the mouse
Toxicology and Applied Pharmacology, 1997Co-Authors: H M Theobald, Richard E. PetersonAbstract:To evaluate effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) exposure on male and female reproductive system development of the mouse, the offspring of pregnant ICR mice administered 0, 15, 30, or 60 microg TCDD/kg on Gestation Day (GD) 14 were examined at the postweanling, pubertal, young adult, and adult stages of development. Dam and offspring body weights and prenatal and postnatal mortality were unaffected by TCDD exposure. The most sensitive endpoints in male offspring were decreased ventral prostate, coagulating gland, and thymus weights, accelerated eye opening, and hydronephrosis. Decreases in pituitary gland weight and epididymal sperm numbers were also found in TCDD-exposed male offspring. Testis, epididymis, and dorsolateral prostate weights, anogenital distance, latencies to testis descent and to preputial separation, and serum testosterone concentrations were unaffected. At the highest maternal TCDD dose uterus weights were decreased in female offspring evaluated during estrus and diestrus. No morphologic changes in the external genitalia of female offspring were found, nor were there alterations in ovary or pituitary gland weights. Cross-species comparisons showed that the mouse was not as sensitive to TCDD-induced developmental reproductive toxicity as the rat and hamster. Many endpoints affected by TCDD in rat and hamster offspring were either not affected or were less sensitive in mouse offspring. Endpoints of androgenic status were not affected in the mouse, decreases in Accessory Sex Organ weights were restricted to fewer Organs in the mouse, and decreases in daily sperm production were not found in the mouse. The only developmental reproductive endpoint observed in all three species was a reduction in epididymal sperm numbers.
John P Durham - One of the best experts on this subject based on the ideXlab platform.
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androgen induced norepinephrine release from postganglionic neurons mediates Accessory Sex Organ smooth muscle proliferation
The Journal of Urology, 2002Co-Authors: Julie Kim, Dennis Cole, Anne Johnson, Virgilio Centenera, Emmanuel Schenkman, John P Durham, Albert J Azzaro, Michael G MawhinneyAbstract:Purpose: Guinea pig seminal vesicle smooth muscle displays an initial androgen dependent, proliferative response during early puberty, followed by progression to an androgen resistant, amitotic state in adults. We determined the role of norepinephrine in androgen dependent pubertal proliferation and in the subsequent terminal differentiation of adult seminal vesicle smooth muscle.Materials and Methods: Guinea pig seminal vesicle provided a suitable model since its unique anatomy allowed clean harvest of smooth muscle without epithelium. Norepinephrine release from postganglionic adrenergic nerve terminals in seminal vesicle smooth muscle was measured using several techniques. Prazosin sensitive electrical field stimulation of contractile responses qualitatively assessed norepinephrine release. Norepinephrine release was quantified directly in vitro from incubated seminal vesicle smooth muscle minces and indirectly ex vivo from intact tissue using the endogenous seminal vesicle smooth muscle concentration ...
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m calpain activation depletion is associated with androgen induced reduction of protein kinase c and proliferation of male Accessory Sex Organ smooth muscles cells
The Journal of Urology, 1997Co-Authors: Norman Gebrosky, Dennis Cole, John P Durham, Caroline Stetterneel, Michael G MawhinneyAbstract:ABSTRACTPurpose: In the guinea pig seminal vesicle smooth muscle (SVM), androgen-dependent proliferation and terminal differentiation appear to be coupled to protein kinase C (PKC). This is based on the observations that both the soluble (cytosolic) enzyme and the Triton X-100 solubilizable form of the particulate enzyme were reduced during proliferation but were androgen-resistant in the amitotic state of adults. The purpose of the present investigation was to determine if the reduction in PKC activity was linked to the translocation of the activated enzyme to acceptor sites in the Triton X-100 insoluble fraction of the cell or reflected enzyme depletion due to proteolysis by androgen-dependent activation of the u- and/or m-calpains.Materials and Methods: SVM was harvested from treated animals, homogenized and separated into soluble and particulate components. The particulate material was further fractionated into Triton X-100 soluble and insoluble fractions. PKC activity was determined in all fractions ...
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protein kinases and the androgen induced proliferation of Accessory Sex Organ smooth muscle
Biology of Reproduction, 1992Co-Authors: Angelo Mariotti, John P Durham, Michael G MawhinneyAbstract:The possible role of second messenger systems in androgen-dependent smooth muscle proliferation was investigated. Focusing on the hormone-sensitive guinea pig seminal vesicle, we analyzed changes in protein kinase C (PKC) and cAMP-dependent type I and II protein kinases during the androgen-dependent smooth muscle proliferation of puberty, as well as in the transition to the nonproliferative state of the adult. The androgenic sensitivity of the cAMP-dependent type I and II protein kinases and the cAMP-dependent phosphorylations of soluble muscle proteins did not correlate with the qualitative change in the androgenic sensitivity of the prepubertal vs. adult animals. In contrast to the cAMP-dependent protein kinases, regulation of the soluble and particulate forms of PKC corresponded to the androgen-induced smooth muscle proliferation. That is, in the seminal vesicle muscle of prepubertal castrated animals, androgen treatment reduced both the soluble and particulate forms of PKC during the increase in smooth muscle DNA synthesis, and in adult seminal vesicle smooth muscle, which was resistant to androgen-induced proliferation, both forms of the enzyme were resistant to androgenic stimulation. It is concluded that PKC may be a component of an autocrine mitogenic mechanism involved in the coupling and uncoupling of androgen-induced smooth muscle proliferation.
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of Accessory Sex Organ smooth muscle1
1992Co-Authors: Angelo Mariotfi, John P Durham, Michael G MawhinneyAbstract:The possible role of second messenger systems in androgen-dependent smooth muscle proliferation was investigated. Focusing on the hormone.sensitive guinea pig seminal vesicle, we analyzed changes in protein kinase C (PKC) and cAMP.dependent type I and 11 protein kinases during the androgen-dependent smooth muscle proliferation of puberty, as well as in the transition to the nonproliferative state of the adult. The androgemc sensitivity of the cAMP-dependent type I and II protein kinases and the cAMP-dependent phosphorylations of soluble muscle proteins did not correlate with the qualitative change in the androgenic sensitivity of the prepubertal vs. adult animals. In contrast to the cAMP-dependent protein kinases, regulation of the soluble and particulate forms of PKC corresponded to the androgen.induced smooth muscle proliferation. That is, in the seminal vesicle muscle of prepubertal castrated animals, androgen treatment reduced both the soluble and particulate forms of PKC during the increase in smooth muscle DNA synthesis, and in adult seminal vesicle smooth muscle, which was resistant to androgen-induced proliferation, both forms of the enzyme were resistant to androgenic stimulation. It is concluded that PKC may be a component of an autocrine mitogenic mechanism involved in the coupling and uncoupling of androgen-induced smooth muscle proliferation.
Ekkehard Schillinger - One of the best experts on this subject based on the ideXlab platform.
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drospirenone a novel progestogen with antimineralocorticoid and antiandrogenic activity
Annals of the New York Academy of Sciences, 1995Co-Authors: Peter Muhn, Rolf Krattenmacher, Ulrike Fuhrmann, Karlheinrich Fritzemeier, Ekkehard SchillingerAbstract:Drospirenone (ZK 30595; 6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17 alpha-pregn-4-ene-21, 17-carbolactone) is a novel progestogen under clinical development. Drospirenone is characterized by an innovative pharmacodynamic profile which is very closely related to that of progesterone. Potential applications include oral contraception, hormone replacement therapy and treatment of hormonal disorders. The pharmacological properties of drospirenone were investigated in vitro by receptor binding and transactivation experiments and in vivo in appropriate animal models. In qualitative agreement with progesterone, the compound binds strongly to the progesterone and the mineralocorticoid receptor and with lower affinity to androgen and glucocorticoid receptors. There is no detectable binding to the estrogen receptor. Steroid hormone agonistic and antagonistic activities of progesterone and drospirenone were compared in transactivation experiments. Individual steroid hormone receptors were artificially expressed together with a reporter gene in appropriate cell lines. Both hormones were unable to induce any androgen receptor-mediated agonistic activity. Rather, both progesterone and drospirenone distinctly antagonized androgen-stimulated transcriptional activation. Likewise, both compounds only very weakly activated the mineralocorticoid receptor but showed potent aldosterone antagonistic activity. Drospirenone did not induce glucocorticoid receptor-driven transactivation. Progesterone was a weak agonist in this respect. Drospirenone exerts potent progestogenic and antigonadotropic activity which was studied in various animal species. It efficiently promotes the maintenance of pregnancy in ovariectomized rats, inhibits ovulation in rats and mice and stimulates endometrial transformation in the rabbit. Furthermore, drospirenone shows potent antigonadotropic, i.e., testosterone-lowering activity in male cynomolgus monkeys. The progestogenic potency of drospirenone was found to be in the range of that of norethisterone acetate. The majority of clinically used progestogens are androgenic. Drospirenone, like progesterone, has no androgenic but rather an antiandrogenic effect. This property was demonstrated in castrated, testosterone propionate substituted male rats by a dose-dependent inhibition of Accessory Sex Organ growth (seminal vesicles, prostate). In this model, the potency of drospirenone was about a third that of cyproterone acetate. Drospirenone, like progesterone, shows antimineralocorticoid activity, which causes moderately increased sodium and water excretion. This is an outstanding characteristic which has not been described for any other synthetic progestogen before. Drospirenone is eight to ten times more effective in this respect than spironolactone. The natriuretic effect was demonstrable for at least three weeks upon daily treatment of rats with a dose of 10 mg/animal. Drospirenone is devoid of any estrogenic, glucocorticoid or antiglucocorticoid activity. In summary, drospirenone, like progesterone, combines potent progestogenic with antimineralocorticoid and antiandrogenic activity in a similar dose range.(ABSTRACT TRUNCATED AT 400 WORDS)
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drospirenone a novel progestogen with antimineralocorticoid and antiandrogenic activity pharmacological characterization in animal models
Contraception, 1995Co-Authors: Peter Muhn, Rolf Krattenmacher, Sybille Beier, Walter Elger, Ekkehard SchillingerAbstract:Drospirenone (ZK 30595; 6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3- oxo-17 alpha-pregn-4-ene-21, 17-carbo-lactone) is a novel progestogen under clinical development. Potential applications include oral contraception, hormone replacement therapy and treatment of hormonal disorders. Drospirenone is characterized by a pharmacodynamic profile very closely related to that of progesterone. The progestogenic activity of drospirenone has been analysed in a variety of animal models. The compound efficiently promotes the maintenance of pregnancy in rats, inhibits ovulation in rats and stimulates endometrial transformation in the rabbit. Furthermore, drospirenone shows potent antigonadotropic, i.e. testosterone-lowering, activity in male cynomolgus monkeys. The progestogenic potency of drospirenone was found to be in the range of that of norethisterone acetate or cyproterone acetate. Like progesterone, drospirenone has been shown to have an antimineralocorticoid effect in rats and humans. It has now been demonstrated that the compound has a long-lasting natriuretic activity in rats on administration of a daily dose of 10 mg s.c. for three weeks. Under identical conditions, spironolactone, a widely-used antimineralocorticoid, becomes ineffective after the initial treatment phase. Drospirenone exhibits antiandrogenic activity in castrated, testosterone-substituted male rats as shown by dose-dependent inhibition of Accessory Sex Organ growth (prostate, seminal vesicles). In this model, the potency of drospirenone was found to be about one-third that of cyproterone acetate. The compound is devoid of androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. Possible drug interaction between drospirenone and ethinylestradiol (EE) was also investigated. EE did not interfere with either the progestogenic or the antimineralocorticoid activity of drospirenone. In conclusion, drospirenone represents a novel type of synthetic progestogen since it combines potent progestogenic characteristics with antimineralocorticoid and antiandrogenic activity. Thus, the pharmacological profile of drospirenone is more closely related to that of the natural hormone progesterone than is that of any other synthetic progestogen in use today. Therefore, drospirenone is anticipated to give rise to a number of additional health benefits both for users of oral contraceptives and hormone replacement therapy recipients.
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drospirenone a novel progestogen with antimineralocorticoid and antiandrogenic activity pharmacological characterization in animal models
Contraception, 1995Co-Authors: Peter Muhn, Rolf Krattenmacher, Sybille Beier, Walter Elger, Ekkehard SchillingerAbstract:Abstract Drospirenone (ZK 30595; 6β, 7β, 15β, 16β-dimethylen-3-oxo-17α-pregn-4-ene-21, 17-carbo-lactone) is a novel progestogen under clinical development. Potential applications include oral contraception, hormone replacement therapy and treatment of hormonal disorders. Drospirenone is characterized by a pharmacodynamic profile very closely related to that of progesterone. The progestogenic activity of drospirenone has been analysed in a variety of animal models. The compound efficiently promotes the maintenance of pregnancy in rats, inhibits ovulation in rats and stimulates endometrial transformation in the rabbit. Furthermore, drospirenone shows potent antigonadotropic, i.e. testosterone-lowering, activity in male cynomolgus monkeys. The progestogenic potency of drospirenone was found to be in the range of that of nore-thisterone acetate or cyproterone acetate. Like progesterone, drospirenone has been shown to have an antimineralocorticoid effect in rats and humans. It has now been demonstrated that the compound has a long-lasting natriuretic activity in rats on administration of a daily dose of 10 mg s.c. for three weeks. Under identical conditions, spironolactone, a widely-used antimineralocorticoid, becomes ineffective after the initial treatment phase. Drospirenone exhibits antiandrogenic activity in castrated, testosterone-substituted male rats as shown by dose-dependent inhibition of Accessory Sex Organ growth (prostate, seminal vesicles). In this model, the potency of drospirenone was found to be about one-third that of cyproterone acetate. The compound is devoid of androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. Possible drug interaction between drospirenone and ethinylestradiol (EE) was also investigated. EE did not interfere with either the progestogenic or the antimineralo-corticoid activity of drospirenone. In conclusion, drospirenone represents a novel type of synthetic progestogen since it combines potent progestogenic characteristics with antimineralocorticoid and antiandrogenic activity. Thus, the pharmacological profile of drospirenone is more closely related to that of the natural hormone progesterone than is that of any other synthetic progestogen in use today. Therefore, drospirenone is anticipated to give rise to a number of additional health benefits both for users of oral contraceptives and hormone replacement therapy recipients.
Dennis Cole - One of the best experts on this subject based on the ideXlab platform.
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androgen induced norepinephrine release from postganglionic neurons mediates Accessory Sex Organ smooth muscle proliferation
The Journal of Urology, 2002Co-Authors: Julie Kim, Dennis Cole, Anne Johnson, Virgilio Centenera, Emmanuel Schenkman, John P Durham, Albert J Azzaro, Michael G MawhinneyAbstract:Purpose: Guinea pig seminal vesicle smooth muscle displays an initial androgen dependent, proliferative response during early puberty, followed by progression to an androgen resistant, amitotic state in adults. We determined the role of norepinephrine in androgen dependent pubertal proliferation and in the subsequent terminal differentiation of adult seminal vesicle smooth muscle.Materials and Methods: Guinea pig seminal vesicle provided a suitable model since its unique anatomy allowed clean harvest of smooth muscle without epithelium. Norepinephrine release from postganglionic adrenergic nerve terminals in seminal vesicle smooth muscle was measured using several techniques. Prazosin sensitive electrical field stimulation of contractile responses qualitatively assessed norepinephrine release. Norepinephrine release was quantified directly in vitro from incubated seminal vesicle smooth muscle minces and indirectly ex vivo from intact tissue using the endogenous seminal vesicle smooth muscle concentration ...
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m calpain activation depletion is associated with androgen induced reduction of protein kinase c and proliferation of male Accessory Sex Organ smooth muscles cells
The Journal of Urology, 1997Co-Authors: Norman Gebrosky, Dennis Cole, John P Durham, Caroline Stetterneel, Michael G MawhinneyAbstract:ABSTRACTPurpose: In the guinea pig seminal vesicle smooth muscle (SVM), androgen-dependent proliferation and terminal differentiation appear to be coupled to protein kinase C (PKC). This is based on the observations that both the soluble (cytosolic) enzyme and the Triton X-100 solubilizable form of the particulate enzyme were reduced during proliferation but were androgen-resistant in the amitotic state of adults. The purpose of the present investigation was to determine if the reduction in PKC activity was linked to the translocation of the activated enzyme to acceptor sites in the Triton X-100 insoluble fraction of the cell or reflected enzyme depletion due to proteolysis by androgen-dependent activation of the u- and/or m-calpains.Materials and Methods: SVM was harvested from treated animals, homogenized and separated into soluble and particulate components. The particulate material was further fractionated into Triton X-100 soluble and insoluble fractions. PKC activity was determined in all fractions ...
