Comparison of the effects of the irreversible aromatase inhibitor exemestane with atamestane and MDL 18962 in rats with DMBA-induced mammary tumours

Zaccheo, T.; Giudici, D.; Ornati, G.; Panzeri, A.; Salle, E. Di

doi:10.1016/0277-5379(91)90313-3

Cited by 33 publications

(15 citation statements)

References 16 publications

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“…However, while recognizing the limited utility of the hormone measurements in this study design in general, the uniformly low values for LH in treated rats were consistent with expectations of effects of exemestane (Zaccheo et al 1991). These lower values were supported by histologic findings including the absence of recent ovulation and atrophy of ovarian interstitial cells (Erickson et al 1985;Freeman 2006).…”

Section: Discussionsupporting

confidence: 79%

Histologic and Cytologic Detection of Endocrine and Reproductive Tract Effects of Exemestane in Female Rats Treated for up to Twenty-eight Days

et al. 2011

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The objective of this study was to determine the shortest period of time necessary to detect histologic evidence of estrous cycle disruption in Sprague-Dawley rats treated for up to 28 days with the aromatase inhibitor exemestane at 1,000 mg/kg. Rats were evaluated on day 5, 8, 15, or 29. Vaginal mucification, uterine and cervical epithelial atrophy, uterine luminal epithelial vacuolation, decreased uterine granulocytes, and hypertrophy/hyperplasia of mammary ducts and alveoli were noted by day 5 and persisted throughout the study. From day 8 to day 29, absence of recent basophilic corpora lutea, increased atresia of antral follicles, interstitial cell hyperplasia, and increased luteinized follicles were present in the ovaries of treated rats. Vaginal smears detected persistent diestrus, confirming estrous cycle disruption between days 5 and 8. Ovary and uterine weights were largely unaffected. Serum hormone levels were not useful due to the study design employed. Other effects of exemestane included decreased adrenal weights and decreased cell size in both the adrenal zona fasciculata and the pituitary pars distalis. While early histologic changes were evident on day 5, only after 8 days of treatment were findings considered sufficient to clearly identify exemestane-induced estrous cycle disruption using microscopy alone.

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Section: Discussionsupporting

confidence: 79%

Histologic and Cytologic Detection of Endocrine and Reproductive Tract Effects of Exemestane in Female Rats Treated for up to Twenty-eight Days

et al. 2011

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“…Unlike similar effects in this model with the steroidal AI exemestane, our previous study [30] showed these bone preserving effects are not blocked by the androgen receptor blocker flutamide [33] and thus appear to be non-androgenic [4,30,34,35]. The mechanism of bone preserving effects of ATA remains unexplained.…”

Section: Discussionmentioning

confidence: 47%

Comparing the effects of atamestane, toremifene and tamoxifen alone and in combination, on bone, serum lipids and uterus in ovariectomized rats

Goss

2009

The Journal of Steroid Biochemistry and Molecular Biology

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“…ATA significantly increased BMD, bone mechanical strength and trabecular bone volume in OVX rats. But these bone preserving effects are not blocked by the androgen receptor blocker flutamide (FLT) [38] and thus appear to be non-androgenic [2,39,40]. ATA had no stimulatory effect on the uterine epithelium in OVX rats indicating an absence of an intrinsic estrogenic signal.…”

Section: Discussionmentioning

confidence: 99%

The effects of atamestane and toremifene alone and in combination compared with letrozole on bone, serum lipids and the uterus in an ovariectomized rat model

Goss

et al. 2006

Breast Cancer Res Treat

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We compared the effects of atamestane (ATA) and toremifene (TOR) alone and in combination, with letrozole (LET) on bone, serum lipids and the uterus in ovariectomized (OVX) rats after 16 weeks of treatment. Compared to OVX controls lumbar vertebral and femoral BMD as well as mechanical strength and trabecular bone volume were significantly greater in animals given ATA, TOR or ATA + TOR. The effects of ATA were not reversed by the androgen receptor blocker, flutamide (FLT). Serum cholesterol, low-density lipoprotein cholesterol and triglycerides were reduced by TOR and ATA + TOR whereas they remained unchanged in animals receiving ATA, ATA + FLT, and LET. The uterine epithelium in OVX animals was equally stimulated by TOR and ATA + TOR and unaffected by ATA or LET. Intact animals had significant atrophy of the uterine epithelium when receiving ATA. In summary, TOR alone or in combination with ATA had a predictable stimulatory effect on bone and the uterine epithelium while reducing key parameters of lipid metabolism. In contrast, ATA but not LET had an unexpected stimulatory effect on the OVX rat's bone and this was not reversed by the anti-androgen FLT leaving this finding unexplained for now. ATA is distinct from LET on end-organ function and this favorable profile makes clinical testing of this steroidal aromatase inhibitor of interest in the clinical setting.

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Comparison of the effects of the irreversible aromatase inhibitor exemestane with atamestane and MDL 18962 in rats with DMBA-induced mammary tumours

Cited by 33 publications

References 16 publications

Histologic and Cytologic Detection of Endocrine and Reproductive Tract Effects of Exemestane in Female Rats Treated for up to Twenty-eight Days

Histologic and Cytologic Detection of Endocrine and Reproductive Tract Effects of Exemestane in Female Rats Treated for up to Twenty-eight Days

Comparing the effects of atamestane, toremifene and tamoxifen alone and in combination, on bone, serum lipids and uterus in ovariectomized rats

The effects of atamestane and toremifene alone and in combination compared with letrozole on bone, serum lipids and the uterus in an ovariectomized rat model

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