Novel, Low Cost, Highly Effective, Handmade Steroid Pellets for Experimental Studies

Sahores, Ana; Luque, Guillermina M.; Wargon, Victoria; May, María; Molinolo, Alfredo A.; Becú-Villalobos, Damasia; Lanari, Claudia; Lamb, Caroline A.

doi:10.1371/journal.pone.0064049

Cited by 18 publications

(18 citation statements)

References 29 publications

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“…T47D (5 × 10 6 ), genetically modified IBH‐6 (10 6 ) or T47D‐YA/B (5 × 10 6 ) cells were inoculated orthotopically into nu/nu (IBH/6) or NOD/LtSz‐scid/IL‐2Rgamma null female mice. One week prior to T47D or T47D‐YA/B inoculation, E 2 silastic pellets containing 0.5 mg E 2 were sc implanted …”

Section: Methodsmentioning

confidence: 99%

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Progestin and antiprogestin responsiveness in breast cancer is driven by the PRA/PRB ratio viaAIB1 or SMRT recruitment to the CCND1 and MYC promoters

Wargon

Riggio

Giulianelli

et al. 2014

Intl Journal of Cancer

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There is emerging interest in understanding the role of progesterone receptors (PRs) in breast cancer. The aim of this study was to investigate the proliferative effect of progestins and antiprogestins depending on the relative expression of the A (PRA) and B (PRB) isoforms of PR. In mifepristone (MFP)-resistant murine carcinomas antiprogestin responsiveness was restored by re-expressing PRA using demethylating agents and histone deacetylase inhibitors. Consistently, in two human breast cancer xenograft models, one manipulated to overexpress PRA or PRB (IBH-6 cells), and the other expressing only PRA (T47D-YA) or PRB (T47D-YB), MFP selectively inhibited the growth of PRA-overexpressing tumors and stimulated IBH-6-PRB xenograft growth. Furthermore, in cells with high or equimolar PRA/PRB ratios, which are stimulated to proliferate in vitro by progestins, and are inhibited by MFP, MPA increased the interaction between PR and the coactivator AIB1, and MFP favored the interaction between PR and the corepressor SMRT. In a PRB-dominant context in which MFP stimulates and MPA inhibits cell proliferation, the opposite interactions were observed. Chromatin immunoprecipitation assays in T47D cells in the presence of MPA or MFP confirmed the interactions between PR and the coregulators at the CCND1 and MYC promoters. SMRT downregulation by siRNA abolished the inhibitory effect of MFP on MYC expression and cell proliferation. Our results indicate that antiprogestins are therapeutic tools that selectively inhibit PRA-overexpressing tumors by increasing the SMRT/AIB1 balance at the CCND1 and MYC promoters.

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Section: Methodsmentioning

confidence: 99%

“…One week prior to T47D or T47D-YA/B inoculation, E 2 silastic pellets containing 0.5 mg E 2 were sc implanted. 23 In vitro studies Primary cultures, 3 H-thymidine uptake (cited in Ref. 5) and cell counting assays 28 were performed as previously described.…”

Section: Cell Linesmentioning

confidence: 99%

Progestin and antiprogestin responsiveness in breast cancer is driven by the PRA/PRB ratio viaAIB1 or SMRT recruitment to the CCND1 and MYC promoters

Wargon

Riggio

Giulianelli

et al. 2014

Intl Journal of Cancer

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“…For 2-week studies, E 2 (Sigma-Aldrich) dosage (0.125 mg per pellet) was chosen on the basis of other reports (43) and our findings. OBHS or CLI (0.25 mg per pellet) was coadministered with E 2 to test their antiestrogenic effects.…”

Section: Methodsmentioning

confidence: 99%

Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis

et al. 2015

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Estrogenic and inflammatory components play key roles in a broad range of diseases including endometriosis, a common estrogen-dependent gynecological disorder in which endometrial tissue creates inflammatory lesions at extrauterine sites, causing pelvic pain and reduced fertility. Current medical therapies focus primarily on reducing systemic levels of estrogens, but these are of limited effectiveness and have considerable side effects. We developed estrogen receptor (ER) ligands, chloroindazole (CLI) and oxabicycloheptene sulfonate (OBHS), which showed strong ER-dependent anti-inflammatory activity in a preclinical model of endometriosis that recapitulates the estrogen dependence and inflammatory responses of the disease in immunocompetent mice and in primary human endometriotic stromal cells in culture. Estrogen-dependent phenomena, including cell proliferation, cyst formation, vascularization, and lesion growth, were all arrested by CLI or OBHS, which prevented lesion expansion and also elicited regression of established lesions, suppressed inflammation, angiogenesis, and neurogenesis in the lesions, and interrupted crosstalk between lesion cells and infiltrating macrophages. Studies in ERα or ERβ knockout mice indicated that ERα is the major mediator of OBHS effectiveness and ERβ is dominant in CLI actions, implying involvement of both ERs in endometriosis. Neither ligand altered estrous cycling or fertility at doses that were effective for suppression of endometriosis. Hence, CLI and OBHS are able to restrain endometriosis by dual suppression of the estrogen-inflammatory axis. Our findings suggest that these compounds have the desired characteristics of preventive and therapeutic agents for clinical endometriosis and possibly other estrogen-driven and inflammation-promoted disorders.

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“…The mixture was extruded from syringes into ropes that were cured overnight. The resulting pellets were cut, weighed, and kept in sterile conditions at 4°C until use (Gurney, 1982;Sahores et al, 2013;Simpson and Vicario, 1991a). Each implant carried approximately 150-200ug of estradiol, and vehicle implants were size matched.…”

Section: Pharmacological Manipulations and Experimental Timelinesmentioning

confidence: 99%

Estrogen and sex-dependent loss of the vocal learning system in female zebra finches

Choe

Tewari

Zhu

et al. 2020

Preprint

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Sex hormones alter the organization of the brain during early development and coordinate various behaviors throughout life. In zebra finches, song learning is limited to males, and the associated song learning brain pathway only matures in males and atrophies in females. This atrophy can be reversed by giving females exogenous estrogen during early post-hatch development, but whether normal male song system development requires estrogen is uncertain. For the first time in songbirds, we administered exemestane, a potent third generation estrogen synthesis inhibitor, from the day of hatching until adulthood. We examined the behavior, brain, and transcriptome of individual song nuclei of these pharmacologically manipulated animals. We found that males with long-term exemestane treatment had diminished male-specific plumage, impaired song learning, but retained normal song nuclei sizes and most, but not all, of their specialized transcriptome. Consistent with prior findings, females with long-term estrogen treatment retained a functional song system, and we further observed their song nuclei had specialized gene expression profiles similar, but not identical to males. We also observed that different song nuclei responded to estrogen manipulation differently, with Area X in the striatum being the most altered by estrogen modulation. These findings support the hypothesis that song learning is an ancestral trait in both sexes, which was subsequently suppressed in females of some species, and that estrogen has come to play a critical role in modulating this suppression as well as refinement of song learning.

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Novel, Low Cost, Highly Effective, Handmade Steroid Pellets for Experimental Studies

Cited by 18 publications

References 29 publications

Progestin and antiprogestin responsiveness in breast cancer is driven by the PRA/PRB ratio viaAIB1 or SMRT recruitment to the CCND1 and MYC promoters

Progestin and antiprogestin responsiveness in breast cancer is driven by the PRA/PRB ratio viaAIB1 or SMRT recruitment to the CCND1 and MYC promoters

Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis

Estrogen and sex-dependent loss of the vocal learning system in female zebra finches

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