Mammary Tumors and Serum Hormones in the Bitch Treated with Medroxyprogesterone Acetate or Progesterone for Four Years

Frank, Doyle; Kirton, K. T.; Murchison, Thomas E.; Quinlan, W.J.; Coleman, Martin E.; Gilbertson, Terry J.; Feenstra, Ernest S.; Kimball, Frances A.

doi:10.1016/s0015-0282(16)43886-0

Cited by 58 publications

(22 citation statements)

References 18 publications

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“…Although basal plasma TSH concentrations were elevated at 8 months after the start of the treatment, they were still within the reference range for TSH in our laboratory. Others found that MPA treatment had no effect on mean circulating TSH levels [20], but several authors have reported that total T4 and/or T3 values increase during the progesteronedominated luteal phase and pregnancy in bitches [58][59][60]. It remains to be seen whether these changes have clinical significance, but the results of the present study emphasize the importance of considering progestin use when studying the hypothalamic-pituitary-thyroid axis.…”

Section: Discussionmentioning

confidence: 50%

“…In the bitch, progestin treatment does not seem to affect mean prolactin [17] and TSH concentrations [20]. Information with regard to pituitary responsiveness of prolactin to suprapituitary stimulation is limited to one study, in which MPA administration did not change prolactin response to TRH in ovariohysterectomized, estradiol-primed bitches [13].…”

Section: Introductionmentioning

confidence: 95%

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Adenohypophyseal function in bitches treated with medroxyprogesterone acetate

Beijerink

Bhatti

Okkens

et al. 2007

Domestic Animal Endocrinology

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The aim of this study was to investigate the effects of treatment with medroxyprogesterone acetate (MPA) on canine adenohypophyseal function. Five Beagle bitches were treated with MPA (10 mg/kg, every 4 weeks) and their adenohypophyseal function was assessed in a combined adenohypophyseal function test. Four hypophysiotropic hormones (CRH, GHRH, GnRH, and TRH) were administered before and 2, 5, 8, and 11 months after the start of MPA treatment, and blood samples for determination of the plasma concentrations of ACTH, cortisol, GH, IGF-1, LH, FSH, prolactin, ␣-MSH, and TSH were collected at −15, 0, 5, 10, 20, 30, and 45 min after suprapituitary stimulation.MPA successfully prevented the occurrence of estrus, ovulation, and a subsequent luteal phase. MPA treatment did not affect basal and GnRH-induced plasma LH concentrations. The basal plasma FSH concentration was significantly higher at 2 months after the start of MPA treatment than before or at 5, 8, and 11 months after the start of treatment. The maximal FSH increment and the AUC for N.J. Beijerink et al. / Domestic Animal Endocrinology xxx (2006) xxx-xxxmonths of MPA treatment. Differences in mean basal plasma GH concentrations before and during treatment were not significant, but MPA treatment resulted in significantly elevated basal plasma IGF-1 concentrations at 8 and 11 months. MPA treatment did not affect basal and stimulated plasma ACTH concentrations, with the exception of a decreased AUC for ACTH at 11 months. In contrast, the maximal cortisol increment and the AUC for cortisol after suprapituitary stimulation were significantly lower during MPA treatment than prior to treatment. MPA treatment did not affect basal plasma concentrations of prolactin, TSH, and ␣-MSH, with the exception of slightly increased basal plasma TSH concentrations at 8 months of treatment. MPA treatment did not affect TRH-induced plasma concentrations of prolactin and TSH.In conclusion, the effects of chronic MPA treatment on adenohypophyseal function included increased FSH secretion, unaffected LH secretion, activation of the mammary GH-induced IGF-I secretion, slightly activated TSH secretion, suppression of the hypothalamic-pituitary-adrenocortical axis, and unaffected secretion of prolactin and ␣-MSH.

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Section: Discussionmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 95%

Adenohypophyseal function in bitches treated with medroxyprogesterone acetate

Beijerink

Bhatti

Okkens

et al. 2007

Domestic Animal Endocrinology

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“…Progestins increase the incidence of spontaneous mammary tumors in dogs (Frank et al, 1979) and mice (Nagasawa et al, 1988). We found that progesterone can promote DMBA-induced mammary carcinogenesis in rats (Wiehle et al, 2007).…”

Section: Prms In In Vivo Experimental Modelsmentioning

confidence: 61%

Progesterone receptor modulators in breast cancer

Wiehle¹,

2014

Turk J Biol

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Breast cancer has been treated successfully with selective estrogen receptor antagonists (SERMs) such as tamoxifen, receptordepleting agents such as fulvestrant, and aromatase inhibitors such as anastrozole. Selective progesterone receptor modulators (SPRMs or PRMs) have not been studied as much and are currently under investigation for inhibition of mammary carcinogenesis in animal models and breast cancer prevention trials in women. They might follow tamoxifen and aromatase inhibitors in the adjuvant treatment of breast cancers with acquired resistance. These uses have not provoked ground-breaking progress or studies and PRMs do not have a high profile. Most in vitro and in vivo studies indicate that PRMs preferentially suppress cell proliferation and also induce apoptosis. In this review we summarized the data on the effects of PRMs and particularly of the antiprogestins RU-486 (mifepristone) and CDB-4124 (Progenta, Proellex or telapristone acetate) on breast cancer models. Both agents have been employed in preclinical and clinical studies for prevention and treatment of breast cancer. This author believes that PRMs should be investigated more intensely.

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“…As a result of endocrine therapy with tamoxifen, ER and PR in breast cancer cells may decrease, but complete loss of receptor does not occur (6)(7)(8). In animal experiments, progestins increase the incidence of spontaneous mammary tumors in dogs (9) and mice (10) and promote dimethylbenzanthracene (DMBA)-induced mammary carcinogenesis in rats (11,12). Using progestin receptor knockout mice (PRKO) mice, the PR has been shown to be specifically important for DMBA carcinogenicity (13), indicating a sensitivity that would not seem to require the ER.…”

Section: Introductionmentioning

confidence: 99%

CDB-4124, a Progesterone Receptor Modulator, Inhibits Mammary Carcinogenesis by Suppressing Cell Proliferation and Inducing Apoptosis

Wiehle

Lantvit

Yamada

et al. 2011

Cancer Prevention Research

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CDB-4124 (Proellex or telapristone acetate) is a modulator of progesterone receptor (PR) signaling, which is currently employed in preclinical studies for prevention and treatment of breast cancer and has been used in clinical studies for treatment of uterine fibroids and endometriosis. Here we provide evidence for its action on steroid hormone-signaling, cell cycle-regulated genes and in vivo on mammary carcinogenesis. When CDB-4124 is given to rats at 200 mg/kg for 24 months, it prevents the development of spontaneous mammary hyperplastic and premalignant lesions. Also, CDB-4124 given as subcutaneous pellets at two different doses suppressed, dose dependently, N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis. The high dose (30 mg, over 84 days) increased tumor latency from 66 AE 24 days to 87 AE 20 days (P < 0.02), decreased incidence from 85% to 35% (P < 0.001), and reduced multiplicity from 3.0 to 1.1 tumors/animal (P < 0.001). Tumor burden decreased from 2.6 g/animal to 0.26 g/animal (P < 0.01). CDB-4124 inhibited cell proliferation and induced apoptosis in MNU-induced mammary tumors, which correlated with a decreased proportion of PR þ tumor cells and with decreased serum progesterone. CDB-4124 did not affect serum estradiol. In a mechanistic study employing T47D cells we found that CDB-4124 suppressed G 1 /G 0 -S transition by inhibiting CDK2 and CDK4 expressions, which correlated with inhibition of estrogen receptor (ER) expression. Taken together, these data indicate that CDB-4124 can suppress the development of precancerous lesions and carcinogen-induced ER þ mammary tumors in rats, and may have implications for prevention and treatment of human breast cancer. Cancer Prev Res; 4(3); 414-24. Ó2011 AACR.

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Mammary Tumors and Serum Hormones in the Bitch Treated with Medroxyprogesterone Acetate or Progesterone for Four Years

Cited by 58 publications

References 18 publications

Adenohypophyseal function in bitches treated with medroxyprogesterone acetate

Adenohypophyseal function in bitches treated with medroxyprogesterone acetate

Progesterone receptor modulators in breast cancer

CDB-4124, a Progesterone Receptor Modulator, Inhibits Mammary Carcinogenesis by Suppressing Cell Proliferation and Inducing Apoptosis

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