Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The benefits of estrogen replacement therapy in postmenopausal women include increased quality of life, relief from specific symptoms, and the prevention of osteoporosis, genitourinary atrophy, and cardiovascular diseases. Despite these advantages, this therapy has been reported to be associated with an increased frequency of endometrial hyperplasia and adenocarcinoma. In order to evaluate a possible relationship between the histological findings and stroma-derived growth regulators, 19 endometrial samples obtained from women undergoing both percutaneous (n = 11) and oral (n = 8) steroid replacement therapy were processed for histological and immunocytochemical evaluation of estrogen receptor (Er), progesterone receptor (Pr), and epidermal growth factor receptor (EGFr). Transdermal estradiol was given for 21 days and 10 mg medroxyprogesterone acetate (MAP) were added to the last 12 days; conjugated equine estrogens were given for 21 days and 10 mg MAP added to the last 12 days. Endometrial samples were obtained between days 17-18 of the sixth month of therapy. Proliferative and hyperplastic endometria showed immunoreactivity against Er, Pr, and EGFr. Atrophic endometria were always negative by immunocytochemistry. Our results suggest: 1) a relationship between histological findings and the receptor examined; 2) a crucial role for EGF in the regulation of endometrial proliferation.
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PMID:Steroid therapy and the endometrium: biological and clinical implications. 206 90

Various aspects of the binding of the synthetic progesteongens, cronolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-acetoxypregn-4-ene-3,20-dione) and medroxyprogesterone acetate (6 alpha-methyl-17 alpha-acetoxypregn-4-ene-3,20-dione, MAP) to uterine cytosol progesterone receptors of the sheep, rabbit and mouse were studied, in an attempt to explain interesting species differences in the biological activity of these steroids. For the sheep, data for binding-site concentration, relative binding affinity (RBA), dissociation constant (Kd) and rates of association and dissociation indicate specific binding of cronolone to the progesterone receptor and these would seem to explain in part the high progestational activity of cronolone in this species. By contrast, with the mouse, there was only a low level of specific binding of cronolone and this appears to explain its inability to maintain pregnancy in this species. Results for the binding activity of cronolone in rabbit uterus were similar to those for the sheep and thus inability of cronolone to maintain pregnancy in the rabbit is not explained by a failure to bind the progesterone receptor. Species differences in binding to the progesterone receptor were also seen with MAP where the RBA, with respect to progesterone, was high in the sheep and rabbit and lower in the mouse. The results, however, do not relate directly to the progestational activity of MAP in these species. Overall, the data indicate that species differences in the binding activity of steroid receptors constitute one factor that causes species-dependent variation in biological responses to progestogens.
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PMID:In vitro binding of progesterone, cronolone and medroxyprogesterone acetate to uterine progesterone receptors of sheep, rabbit and mouse. 247 58

The anti-tumor activities of steroid compounds on endometrical cancer (Ishikawa cell line) were examined in vitro by human tumor clonogenic assay (HT CA). Clinically effective progestational compounds including medroxyprogesterone acetate (MAP), and 17 alpha hydroxy-progesterone caproate were effective. Norethindrone (ENT), which is also a potent progestational compound, and RU486, which is known to be a progesterone antagonist were ineffective in this in vitro system, neither having any influence on the effect of MAP. These results indicated that the anti-tumor activity of MAP did not proceed via the so-called progesterone receptor system. Morphological changes induced by MAP in undifferentiated endometrial cancer, the effectiveness of tamoxifen, hormonochemotherapy, and the use of MAP for adjuvant therapy and prophylaxis were also discussed.
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PMID:[Hormone dependency and progestogen therapy in the treatment of endometrial cancer]. 295 4

Based upon preliminary observations that tumor response to MPA was correlated to cortisol suppression 42 patients were treated with MPA at different dose levels. 1500 mg MPA p.o. almost completely suppressed endogenous cortisol production in 23 out of 23 patients. Consequently, 51 patients with advanced stage metastatic breast cancer were treated with Medroxyprogesteroneacetate (HD-MAP) at a dosage of 1500 mg p.o. daily or 500 mg i.m. on 5 days per week. There were 5 complete and 7 partical remissions, 23 patients with no change and 10 with progressive disease. 7 patients were not evaluable. Clinical results correlated to plasma cortisol and prolactin blood levels bot not to LH, FSH, TSH, TBI, T3, T4, ACTH and aldosterone measurements. There was no patient with relapse and suppressed cortisol or normal prolactin measurements. The development of pituituary resistance to MPA is suggested. HD-MPA was equally effective in estrogen and/or progesterone receptor positive as in receptor negative patients. It is proposed that cortisol and prolactin determinations are useful to monitor for effective MPA treatment and the early detection of MPA resistance.
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PMID:[High dose medroxyprogesteroneacetate in metastasizing breast cancer: correlations between course of the disease and hormone profiles]. 622 46

A method for determining cytoplasmic progesterone receptor was standardized in normal human endometrium comparing two different tracers, 3H-progesterone (3H-P) and 3H-medroxyprogesterone acetate (3H-MAP), a synthetic progestin which does not bind to Corticosteroid Binding Globulin (CBG). Receptor assays were performed as previously reported for 17beta-estradiol receptor, with slight modifications: incubation lasted 1 hr at 0 degree C, followed by 5 min DCC exposure under the same conditions. When 3H-P was employed as tracer, blanks performed with cold MAP gave similar results as using cortisol in incubation tubes and progesterone and cortisol in blanks. 3H-MAP was a good tracer for progesterone receptor because it neither bound to CBG nor to androgen or cortisol receptors; it had very high affinity and specificity for P-R; it was not metabolized by cytosol at 0 degree C and, finally, it detected receptor amounts quite comparable to those obtained using 3H-P.
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PMID:[Determination of cytoplasmic receptors for specific steroid hormones. III) Progestin receptor]. 1795 34

In vitro maturation of oocytes is a crucial step in assisted reproductive technologies in cattle; however, the molecular mechanisms of cumulus contribution to oocyte developmental potential require more investigation. Based on transcriptomic data, we studied by using real-time RT-PCR and western blot in bovine cumulus cells, the kinetics of expression of several candidate genes involved in oxidative stress response, apoptosis, steroid metabolism and signal transmission throughout IVM. Phosphorylations of the components of the main signaling pathways were also analyzed. In addition, IVM was performed in different maturation mediums which influenced the cumulus apoptosis, progesterone secretion and oocyte developmental competence. Glutathione-S-transferase A1 (GSTA1) transcript and protein abundance significantly decreased throughout IVM progression. Similarly, transcript levels of FSH receptor and aromatase (CYP19A1) and protein levels of three steroidogenic enzymes (steroidogenic acute regulatory protein, cytochrome P450scc and 3-beta-hydroxysteroid dehydrogenase) decreased along with progression of maturation and especially since 10 hours of IVM. Expression of progesterone receptor (PGR) and clusterin (CLU) mRNA and phosphorylations of protein kinases AKT, MAPK P38 and SMAD2 were particularly increased at 10 hours of IVM. This expression pattern supposed the role of these factors during oocyte metaphase-I check point of meiosis. Levels of CLU, GSTA1 and FSHR transcripts were higher in 199 basic hormone-free medium as compared to the medium 199EM, enriched in gonadotropins and growth factors, in which we recorded the higher developmental rate and progesterone secretion. Higher phosphorylation levels of SMAD2, AKT and MAP kinase JNK1, but not of MAP kinases ERK1/ERK2 or P38, was positively correlated with oocyte developmental competence and progesterone secretion and negatively correlated with cumulus apoptosis rate. These factors and signaling pathways in cumulus cells are potentially involved in controlling different stages of oocyte nuclear maturation and acquirement of its developmental potential.
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PMID:Kinetics of gene expression and signaling in bovine cumulus cells throughout IVM in different mediums in relation to oocyte developmental competence, cumulus apoptosis and progesterone secretion. 2096 3