Effect Of Medroxyprogesterone Acetate Research Articles

Differential Effects of Progestin and Relaxin on the Synthesis and Secretion of Immunoreactive Prolactin in Long Term Culture of Human Endometrial Stromal Cells*

PRL secretion from human endometrium is a continuous process extending from the luteal phase of the menstrual cycle throughout the entire gestational stage. We have developed a long term primary cell culture system to elucidate the hormonal requirements for this sustained production of PRL. The effects of medroxyprogesterone acetate (MPA), progesterone, and relaxin (RLX) on the production of immunoreactive PRL were investigated. MPA stimulated cell growth and PRL production rate during days 5-20 of culture. Progesterone was 20-40% less effective in stimulating PRL than MPA. Stimulation of PRL was continued 1-2 weeks after MPA withdrawal. Relaxin did not promote cell growth. However, it induced the PRL production which fluctuated during the long term culture. The maximal response to RLX was 2- to 3-fold higher or similar to that of MPA. Only five of nine endometrial specimens examined responded to RLX alone. The effect of MPA plus RLX was significantly greater than that of MPA or RLX alone. The highest production rate was shown in cells treated with MPA and then RLX in sequence. After a month of culture, the production rates (micrograms of PRL per 0.1 mg cell DNA/day) under various culture conditions (A, control; B, MPA; C, MPA for 10-15 days and no hormone afterward; D, both MPA and RLX; and E, MPA and RLX in sequence) were: A, about 0-0.01 (n = 12); B, 2.5 +/- 0.9 (n = 8); C, 4.8 +/- 2.5 (n = 8); D, 5.7 +/- 3.0 (n = 5); and E, 11 +/- 3.7 (n = 7); mean +/- SD; n, number of specimens). Endometrial stromal cells were incubated with [35S]methionine, and [35S]immunoreactive PRL and other secretory proteins were analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis to characterize the size and isoforms of immunoreactive PRL. PRL was one of the five major secretory proteins (23-25K, 32K, 42K, 78K, and 150K daltons, sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing condition) induced by MPA and RLX in endometrial stromal cells. More than 90% of immunoreactive PRL was secreted into the medium. The apparent mol wt of immunoreactive PRL were 21K, 23K (the predominant size), and 25K daltons. Results obtained from the incorporation of [14C]glucosamine into immunoreactive PRL indicated that both 23K and 25K PRL contained glycosylated PRL. A 45K-dalton glycosylated immunoreactive PRL was also present in the culture medium.(ABSTRACT TRUNCATED AT 400 WORDS)

Histidine potentiates the antiproliferative effect of medroxyprogesterone acetate (MPA) on a human breast cancer cell line

Histidine potentiates the antiproliferative effect of medroxyprogesterone acetate (MPA) on a human breast cancer cell line

核DNA量による乳癌の悪性度判定ならびに内分泌療法の作用機序の研究 -Flow cytometryによる解析-

核DNA量による乳癌の悪性度判定ならびに内分泌療法の作用機序の研究 -Flow cytometryによる解析-

The effect of medroxyprogesterone acetate (Provera) on ovarian radiosensitivity

Medroxyprogesterone acetate (Provera) is a drug that is commonly given to young women with cancer during chemotherapy and radiation to control heavy bleeding associated with anovulation. Because hypothalamic-pituitary-ovarian suppression has been associated with ovarian protection from the effects of chemotherapy and medroxyprogesterone acetate has been identified as a radiosensitizing agent, we explored the effects of medroxyprogesterone acetate on a rat model with known radiation injury characteristics. Sprague-Dawley rats were treated with medroxyprogesterone acetate or vehicle from day 22 to day 37 of life and were either irradiated or sham-irradiated on day 30 of life and then killed on day 44. Radiation with medroxyprogesterone acetate administration produced a greater loss in preantral and healthy control follicles than in control follicles. No suppression of luteinizing hormone or follicle-stimulating hormone had occurred by day 30 but ovarian glutathione content was reduced. These findings indicate that the administration of medroxyprogesterone acetate with radiotherapy may enhance ovarian injury.

Effect of medroxyprogesterone acetate on the response of the rat mammary gland to carcinogenesis

In order to determine whether mammary gland differentiation, which is known to protect this organ from chemically induced carcinogenesis, can be stimulated in virgin rats by administration of a progestagenic agent, medroxyprogesterone acetate (MPA) was given to 300 Sprague-Dawley virgin rats, which at the ages of 45, 55, 65 and 75 days, groups I, II, III and IV respectively, had implanted an MPA pellet of 0.5 mg (low dose-LD) or 5.0 mg (high dose-HD). Pellets were removed after 21 days, and 21 days later five animals per group were killed for evaluation of mammary gland development. The remaining animals received 8 mg 7,12-dimethylbenz(a)-anthracene (DMBA) per 100 g body weight, and were killed after 24 weeks for evaluation of tumour incidence. Both age and treatment affected mammary gland structure and had a significant interaction in the proportion of terminal end buds (TEBs) present. The number of TEBs decreased as a function of age; treatment at both LD and HD did not modify the proportion of TEBs in groups I and III; LD decreased their percentage in group II, and both doses markedly increased TEB percentage in group IV animals. MPA LD treatment did not affect overall tumour and adenocarcinoma incidence although group IV animals developed greater incidences than their respective controls. MPA HD treated rats were 2.45 times more likely to develop tumours than their respective controls. Adenocarcinoma incidence had a significant positive correlation with the percentage of TEBs present. It was concluded that this progestagenic agent did not increase the risk of carcinoma development when administered to virgin rats at the clinical dose used for contraception. However, a 10-fold dose increase resulted in a higher tumorigenic response.

The effect of medroxyprogesterone acetate on aromatase and DNA polymerase α activities in breast tumours

The effect of treatment with the progestogen medroxyprogesterone acetate (MPA) on the peripheral conversion of androstenedione to oestrone and tumour aromatase activity has been examined in post-menopausal women with advanced breast cancer. In addition to being a potent progestational compound, MPA also possesses glucocorticoid properties and glucocorticoids have been shown to stimulate in vitro aromatase activity. While some evidence was obtained of an increase in aromatase activity in tumour tissue after treatment with MPA, peripheral conversion of androstenedione to oestrone was similar when measured before (2.12 +/- 0.67%) and after (1.89 +/- 0.16%) treatment. DNA polymerase alpha activity, measured as a marker of cellular proliferation, decreased from 331 +/- 145 to 156 +/- 93 pmol thymidine triphosphate (TTP)/mg protein per h (P less than 0.02) in tumour samples examined before and after treatment. It is concluded that treatment with high doses of MPA has no effect on the peripheral conversion of androstenedione to oestrone but results in a significant reduction in tumour DNA polymerase alpha activity.

Effects of medroxyprogesterone acetate (MPA) on phosphodiesterase (PDE) activity in DMBA-induced rat mammary tumours

Effects of medroxyprogesterone acetate (MPA) on phosphodiesterase (PDE) activity in DMBA-induced rat mammary tumours

Immunohistological localization of pregnancyassociated endometrial α2‐globulin (α2‐PEG) in endometrial adenocarcinoma and effect of medroxyprogesterone acetate

Endometrium from postmenopausal women with endometrial adenocarcinoma was examined immunohistochemically using a monoclonal antibody to pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the glandular epithelium during the late luteal phase of the menstrual cycle and early pregnancy. Specimens were obtained at initial diagnostic curettage and at hysterectomy after medroxyprogesterone acetate (MPA) therapy. alpha 2-PEG was not detected in any malignant tissue irrespective of histological differentiation. Non-malignant endometrium obtained in association with malignant tissue was negative for alpha 2-PEG before treatment although after MPA therapy all specimens obtained exhibited marked alpha 2-PEG localization in glands. In four specimens endogenous alkaline phosphatase was observed consistently only in the malignant endometrium. Malignant endometrium does not appear to synthesize alpha 2-PEG nor is its synthesis induced by an oral progestogen, so that it does not represent a useful marker for endometrial carcinoma. Non-malignant endometrium in postmenopausal women appears to be fully capable of alpha 2-PEG production after stimulation with an oral progestogen.

Effects of medroxyprogesterone acetate on serum prolactin levels and liver prolactin binding capacity in the rat

Modifications in liver prolactin (PRL) receptor levels and serum PRL concentration induced by administration of medroxyprogesterone acetate (MPA) were investigated in rats of both sexes. MPA induced a reduction both of the levels of PRL in the serum and of liver PRL receptors in the female rat. The reduction of the number of PRL receptors caused by MPA was rapid and almost complete after 10 days of treatment and appeared earlier than that of serum PRL levels. Furthermore the MPA-induced decrease in PRL receptors was specific, since insulin binding to the same liver membranes was not affected. MPA given simultaneously with oestradiol (which increases both the number of liver PRL receptors and the serum PRL levels in the male rats) was able to counteract the increase in PRL binding induced by oestradiol. On the contrary, the oestrogen-induced increase in serum PRL was not affected by MPA treatment. Similar results were obtained using tamoxifen, a well known antioestrogenic drug. In conclusion, our results show that the reduction of PRL receptor levels induced by MPA in rat liver is specific, not correlated to serum PRL concentration, and seems to depend on the antioestrogenic activity of the drug.

Inhibitory effects of danazol and medroxyprogesterone acetate on [ 3H]thymidine incorporation in human endometrial cancer cells

Effects of medroxyprogesterone acetate (MPA) and danazol (1 nM–10 μM) on cultured cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were simultaneously investigated. Of twenty-four endometrial adenocarcinomas examined, five tumors were successfully maintained in primary cell culture. The addition of MPA as well as danazol in culture of cells from the five tumors resulted in a significant inhibition of [ 3H]thymidine incorporation in cancer cells from three tumors having progesterone receptors (PR). The minimum effective concentrations of MPA and danazol for the inhibition of [ 3H]thymidine incorporation were found to be 10 and 100 nM, respectively. The difference in effective concentration could be explained by a higher affinity of MPA to PR than that of danazol in cancer cells. On the other hand, neither danazol nor MPA affected [ 3H]thymidine incorporation in cultured cells from the remaining two tumors, in which PR was absent in one but was present in the other. These findings, together with our previous findings that danazol inhibited the growth of a human endometrial cancer cell line with PR, suggest that a growth-inhibitory effect of danazol on human endometrial cancer cells is mediated through PR in the cells.

Effects of medroxyprogesterone acetate on plasma testosterone and sexual behavior in male cynomolgus monkeys (Macaca fascicularis)

Medroxyprogesterone acetate (MPA), a synthetic progestin with androgen-depleting activity, is used to treat the deviant sexual behavior of men. To investigate the effects of MPA in another anthropoid primate, 16 oppositely-sexed pairs of cynomolgus monkeys were observed in one-hour behavior tests during 15 successive 4-week periods conducted before, during and after administering to males weekly IM injections of first 20 mg and then 40 mg MPA. The doses used were comparable on a body weight basis to those employed clinically. Blood samples were collected weekly and assayed for plasma testosterone. During MPA treatment both plasma testosterone and ejaculatory behavior were significantly decreased, but the changes in behavior were less marked than the changes in hormone levels. There were clear differences between individual males in the effects of treatment, and the identity and hormonal status of the female partners also influenced the results. During the 6 month withdrawal period, effects were only partially reversible, and the data suggested that the behavioral changes depended on the hormonal changes rather than the opposite. However, a direct central action of MPA on behavioral mechanisms could not be excluded.

Effects of medroxyprogesterone acetate on sleep of healthy young male adults.

The effects of a single 100 mg dose of medroxyprogesterone acetate (MPA) on human sleep were investigated using healthy young male adults. After a baseline night recording, two consecutive MPA nights and the following two withdrawal nights were recorded. The total sleep time was reduced after the 2nd MPA night and the decrease was significant on the 1st withdrawal night. The time of intrasleep awakening increased after the 2nd MPA night. Stage 1 sleep increased significantly on the 2nd MPA and 1st withdrawal nights. Stage 4 sleep decreased and the sleep latency gradually increased after the MPA administration. REM sleep reduced slightly on the 1st withdrawal night. These results indicate that MPA has a mild arousal action on human sleep and that the action may be pronounced a few days after administration of MPA.

Medroxyprogesterone acetate in non‐metastatic gestational trophoblastic disease

The effect of medroxyprogesterone acetate (MPA: Depo-Provera, Upjohn) as a contraceptive agent was assessed in 45 patients with non-metastatic gestational trophoblastic disease and compared with 13 patients using hormonal and 26 patients using non-hormonal methods of contraception. In the whole group of 84 patients 18 (21.4%) required chemotherapy. There was no statistically significant difference in the incidence of persistent trophoblastic disease between MPA (9/45) and the oral contraceptive group (2/13) and MPA and the non-hormonal contraceptive groups (7/26).

Effect of medroxyprogesterone acetate, alone or in combination with epirubicin hydrochloride, on the growth of the Dunning R3327H prostatic adenocarcinoma.

Rats bearing the Dunning R3327H prostatic adenocarcinoma were castrated and supplemented with testosterone propionate. Some of the testosterone-supplemented rats were treated with medroxyprogesterone acetate (MPA) alone or in combination with epirubicin hydrochloride. During the treatment period of 4 weeks, the growth rate of the prostatic tumors was measured. The testosterone-supplemented rats showed a tumor growth rate similar to that found in intact control rats. It was found that MPA has an inhibitory effect on the tumor growth rate in castrated testosterone-supplemented animals. This effect was more pronounced if the MPA treatment was combined with epirubicin hydrochloride, where the tumor growth rate was slower than that found in rats castrated as the only treatment.

8 Myeloprotective effect of medroxyprogesterone acetate (MPA) on committed granulupoietic stemcells under cytotoxic chemotherapy

8 Myeloprotective effect of medroxyprogesterone acetate (MPA) on committed granulupoietic stemcells under cytotoxic chemotherapy

Effect of medroxyprogesterone acetate on hepatic and placental drug metabolism in rats

Effect of medroxyprogesterone acetate on hepatic and placental drug metabolism in rats

Inhibitory Effect of Medroxyprogesterone Acetate on Foreign Body Tumorigenesis in Mice

This paper reports on the investigation of the effect of medroxyprogesterone acetate (MPA) on foreign body tumorigenesis that resulted from sc implantation of a glass cylinder. Adult BALB/c mice of both sexes bearing the foreign body were separated into groups. Group 1 received 40 mg MPA sc every 2 months during 1 year, in the vicinity of the glass cylinder; group 2 received the same MPA treatment in the contralateral flank; and group 3 received no hormonal treatment. Sarcomas developed in 4 of 39, 9 of 41, and 17 of 39 mice, respectively. With the use of an evaluation based on the number of high-risk mice per time interval, the MPA inhibitory effect was found to be statistically significant in both groups: 26, 53, and 79% tumor incidence, respectively. A decrease in the rate of tumor development also was observed but only in mice treated with MPA in situ. An unexpected side effect of continuous MPA administration in females was the appearance of adenocarcinomas.

Effects of Medroxyprogesterone Acetate on Human Breast Cancer Cells in Culturea

Effects of Medroxyprogesterone Acetate on Human Breast Cancer Cells in Culture^a

Endocrine effects of medroxyprogesterone acetate (MPA) and their importance in breast cancer therapy

Endocrine effects of medroxyprogesterone acetate (MPA) and their importance in breast cancer therapy

The effects of medroxyprogesterone acetate on enzyme activities in human endometrial carcinoma

Creatine kinase (CK), isocitrate (ICDH) and glucose-6-phosphate dehydrogenase (G-6-PD) activities and cytosol oestrogen (RE c) and progestin (RP c) receptors have been measured in twenty post-menopausal subjects with endometrial carcinoma. Diagnostic curettage and hysterectomy specimens were obtained from each patient with intervening medroxyprogesterone acetate therapy (MPA). In RP c rich tumours the activity of creatine kinase was significantly increased following MPA and was attributed to an increase in the BB-isoform. There was a similar though less significant increase in ICDH activity. Neither CK nor ICDH were significantly increased following MPA therapy in progesterone receptor poor specimens. There was a small but significant increase in G-6-PD activity following MPA regardless of RP c content. RE c was decreased in some but not all RP c rich tumours following MPA and the trend was significant. The highly significant increase in CK activity confirms the apparent response of this enzyme to progesterone in normal human endometrium during the menstrual cycle.