A radioimmunoassay for serum medroxyprogesterone acetate

Shrimanker, K.; Saxena, B.N.; Fotherby, K.

doi:10.1016/0022-4731(78)90631-3

Cited by 54 publications

(15 citation statements)

References 15 publications

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“…The pysiological concentration detected in serum ranges from 0.1-10 nM in women using HRT [8,20,21]. We treated the cells with two different concentrations of progesterone/progestins reflecting the serum levels detected after HRT use.…”

Section: Discussionmentioning

confidence: 99%

Progesterone and levonorgestrel regulate expression of 17βHSD-enzymes in progesterone receptor positive breast cancer cell line T47D

Sivik

Jansson

2012

Biochemical and Biophysical Research Communications

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The use of combined hormone replacement therapy (HRT) with oestrogens and progestins in postmenopausal women has been associated with an increased risk for developing breast cancer. The reasons are not fully understood, but influence of HRT on endogenous conversion of female sex hormones may be involved. The expression of 17 beta hydroxysteroid dehydrogenases (17βHSD), which are enzymes catalysing the conversion between more or less potent oestrogens, may partly be regulated by progestins. The breast cancer cell lines T47D, MCF-7 and ZR75-1 were treated with progesterone, medroxyprogesterone acetate (MPA) or levonorgestrel for 48 and 72 hours at 10 -7 M and 10 -9 M to investigate influence on 17βHSD1, 17βHSD2 and 17βHSD5 mRNA expression measured by real time PCR. The expression of 17βHSD1 increased in progesterone and levonorgestrel treated T47D cells (48h 10 -7 M P=0.002; P<0.001) and 17βHSD5 increased after progesterone treatment (48 h 10 -7 M P=0.003), whereas the expression of 17βHSD2 decreased after the (48 h 10 -7 M P=0.003; P<0.001). Similar, but less prominent effects were seen in MCF7 and ZR75-1. The progestin effects on 17βHSD-expression were lost when T47D-cells were co-treated with progestins and the progesterone receptor (PgR) inhibitor mifprestone. We show that both reductive (17βHSD1 and 17βHSD5) and oxidative (17βHSD2) members of the 17βHSD-family are under control of progesterone and progestins in breast cancer cell lines. This is most clear in T47D cells which have high PgR expression. 17βHSD enzymes are important players in the regulation of sex steroids locally in breast tumours and tumoural expression of various 17βHSD-enzymes have prognostic and treatment predictive relevance. We propose a mechanism for increased breast cancer risk after HRT in which hormone replacement affects the expression of 17βHSD-enzymes, favouring the expression of reductive enzymes, which in turn could increase levels of bioactive and mitogenic estrogens in local tissue, e.g. breast tissue.

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Section: Discussionmentioning

confidence: 99%

Progesterone and levonorgestrel regulate expression of 17βHSD-enzymes in progesterone receptor positive breast cancer cell line T47D

Sivik

Jansson

2012

Biochemical and Biophysical Research Communications

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“…Assay methods Serum levels of MPA were measured by radioimmunoassay largely according to the method described by Shrimanker et al (1978), using antiserum (kindly donated by Dr K. Fotherby) which was characterised in detail in that report. In brief, 50p!…”

Section: Methodsmentioning

confidence: 99%

The pharmacokinetics of medroxyprogesterone acetate following two different loading dose schedules in advanced carcinoma of the breast

Canney

Dowsett²,

Priestman³

1988

Br J Cancer

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Summary A loading dose of MPA employing a regimen of 1,000mg six hourly for 8 doses can achieve plateau levels above 100 ng ml -1 within the first 36 h of treatment, without any untoward toxicity. This raises the possibility of shortening the time to response for this agent. The additional factor of the time required to achieve adequate serum levels may explain the apparent contradictions between reports correlating response rates and dose and those correlating serum level and response.

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“…Medroxyprogesterone acetate levels were measured in the serum samples by radioimmunoassay (Shrimanker et al, 1978), blood being taken before treatment, weekly during induction and monthly thereafter. Following venepuncture the blood was allowed to clot and the serum separated and stored at -20°until analysed.…”

Section: Methodsmentioning

confidence: 99%

An evaluation of high-dose medroxyprogesterone acetate (MPA) therapy in women with advanced breast cancer

Johnson¹,

Priestman²,

Fotherby³

et al. 1984

Br J Cancer

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Summary The efficacy of high-dose intramuscular MPA therapy in controlling progressive measurable metastatic breast carcinoma was assessed in 32 women. In addition serial measurements of MPA blood levels were carried out in 20 of the patients and subjective effects of treatment were monitored in detail in 18 of the women. Overall 6 patients (19%) gained an objective response and a further 7 (22%) experienced disease stasis from 4-17 months whilst on treatment. Significant differences in serum MPA levels were seen between responders and non-responders, objective tumour shrinkage only being seen in those patients who rapidly attained, and sustained, blood levels in excess of 100ngml-1. Subjective assessment showed no evidence of a euphoriant effect of MPA therapy in the non-responders group.Reports of high-dose Medroxyprogesterone acetate (MPA) administration in the treatment of advanced breast cancer began to appear in the mid 1970s and in 1979 a review of the published data concluded that an objective remission rate of 40% was seen in women who had not previously received cytotoxic therapy (Ganzina, 1979). In addition to objective benefit the relative lack of toxicity of MPA combined with its ability to relieve pain (Pannuti et al., 1979), improve performance status (Ganzia, 1979), and increase appetite and body weight (Cavalli et al., 1983) led to the view that treatment carried a significant subjective benefit. Clinical trials showed that daily intramuscular doses of MPA of 500 mg or more were necessary for a significant incidence of response (Ganzina, 1979), but pharmacokinetic studies have indicated considerable differences in bioavailability between patients (Salimtschik et al., 1980). The present study set out across the objective response to high-dose MPA in women with advanced breast cancer and also to monitor both serum MPA levels and subjective effects of treatment in order to identify any correlations between these three parameters. Materials and methodsThe study was designed as an open, single group assessment and women with evaluable, progressing, locally recurrent or metastatic carcinoma of the breast which had failed to respond to, or relapsed after, conventional therapy were enrolled. Objectives response was assessed at monthly intervals and UICC criteria were adopted (Hayward et al., 1977

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A radioimmunoassay for serum medroxyprogesterone acetate

Cited by 54 publications

References 15 publications

Progesterone and levonorgestrel regulate expression of 17βHSD-enzymes in progesterone receptor positive breast cancer cell line T47D

Progesterone and levonorgestrel regulate expression of 17βHSD-enzymes in progesterone receptor positive breast cancer cell line T47D

The pharmacokinetics of medroxyprogesterone acetate following two different loading dose schedules in advanced carcinoma of the breast

An evaluation of high-dose medroxyprogesterone acetate (MPA) therapy in women with advanced breast cancer

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