Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The estrogenic effects of MER-25, an antiestrogen, on eating and body weight were studied in rats. As evidenced by its failure to cause an habitual aversion to saccharin and failure to alter spontaneous activity, MER-25 inhibited weight gain and eating. Estradiol benzoate (EB) and MER-25 both had similar effects in gonadectomized rats, and produced a transient decrease in food consumption and a permanent decrease in body weight. Progesterone ameliorated the effect of both agents on eating and body weight. MER-25 and EB were both more active in females than males. MER-25 did not markedly alter the effects of EB on body weight and eating, but did antagonize the effects of EB on the uterus, vagina, and sex behavior. The results indicate biochemical differences between the effects of estrogens on eating and body weight and other estrogen-dependent processes.
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PMID:Estrogenic effects of an antiestrogen, MER-25, on eating and body weight in rats. 94 84

Progesterone priming of the ovariectomized rat, followed by a single injection of estradiol-17beta (10 mug) is followed by an increased uterine synthesis of both PGF and PGE. The administration of an estrogen antagonist (MER-25; 10 mg) concomitantly with estradiol had no effect on uterine prostaglandin synthesis. Similarly, the administration of either Actinomycin D or cycloheximide, antibiotics demonstrated to inhibit mRNA and protein synthesis, respectively, is without effect on estrogen-stimulated uterine prostaglandin synthesis. These results are considered with regard to the classic receptor theory of estrogen action and are a preliminary indication that estrogen-stimulated uterine prostaglandin synthesis may not require those receptor mediated events.
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PMID:Considerations into the mechanism of estrogen-stimulated uterine prostaglandin synthesis. 95 89

Clam oocytes are arrested naturally at the G2/M border in meiosis and contain an inactive 42 kDa ERK/MAP kinase, p42MAPK. Following fertilization, p42MAPK is rapidly phosphorylated on tyrosine residues and concomitantly activated. Both tyrosine phosphorylation and activation of p42MAPK begin within 2-3 min of fertilization, peak at approximately 15 min, then rapidly decline and disappear around the end of meiosis I. Neither the tyrosine phosphorylated form of p42MAPK nor p42MAPK activity reappears during meiosis II or the succeeding mitotic cell cycles. High doses of molybdate, a potent PTPase inhibitor, block the phosphorylation of p42MAPK and entry into the cell cycle. Lower doses of molybdate delay both p42MAPK phosphorylation and the release from cell cycle arrest, but once cells have re-entered the cell cycle, they continue with near-normal timing. These results argue that the transient activation of p42MAPK at fertilization is a one-time event linked to release from cell cycle arrest. In trying to reconcile this one-time activation of p42MAPK in clam embryos with the recurring, M-phase specific activation of MBP/MAP kinases reported in other systems, we show that cdc2 kinase contributes a major portion of the MBP kinase activity in mitotic extracts. Furthermore, a small fraction of p42MAPK and other related kinases are present in p13suc1-bound material, cautioning against the use of p13suc1 beads for experiments where, in addition to cdc2, the unaccounted presence of other kinase activities could be misleading.
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PMID:Activation of p42 MAP kinase and the release of oocytes from cell cycle arrest. 132 52

Weight gain and psychomotor development of breastfed infants of Egyptian mothers using Norplant, Cu T-380A IUDs, norethisterone enanthate injectables (NET-EN), Depo Provera and a levonorgestrel minipill were compared in 2 trials. First, groups of 120 women using Norplant and NET-EN were compared to a control group using IUDs, beginning 5-7 weeks postpartum. There were no differences in infant weight gain, mid-arm circumference, triceps-skin-fold thickness, or timing of motor milestones. The mean growth curve of all 3 groups were close to that of the 50th percentile for Egyptian infants. While timing of initiation of supplements was similar in the 3 groups, complete weaning occurred first in the IUD group, second in the Norplant group, and last in the NET-EN users. A second trail compared progesterone implants injected with a trocar that resulted in a blood level of 3 ng/ml for 5 months, with Population Council vaginal rings releasing 10 progesterone/24 hours, and CuT-380A IUDs. Serum progesterone in the ring users averaged 5.2 ng/ml for the 1st 2 weeks, then leveled off at about 4 ng/ml for about 2 months, falling to about 3 ng/ml for the last 3 weeks of use. Each women used 4 rings per year. Evidence of ovulation by ultrasonic vaginal probe and assay of estradiol and progesterone was apparent in 25% of vaginal ring users, compared to 55.9% of controls in the 2nd 6 months postpartum. There was 1 pregnancy in a ring users. The continuation rates were 66.6% for rings and 85.5% for IUDs. The reasons for discontinuation in vaginal ring continuation were logistical problems and unfamiliarity.
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PMID:Contraception with progestogens and progesterone during lactation. 183 50

A survey of recent trials of new injectable hormonal contraceptives, progestogen-only, levonorgestrel esters, and once monthly injectables, follows a brief review of all the experimental long-acting contraceptive modalities, injectables, implants, vaginal rings, and hormone-releasing IUDs. Currently medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) are being used by 7 million women. WHO is conducting dose reduction trials and studies of bioavailability in various national populations. Even though a dose of 100 mg DMPA every 3 months has been satisfactory for contraception, 150 mg is still recommended until further pharmacodynamic data are available. Some populations, notably Thais and Mexican women, have higher peaks and more rapid elimination rates of DMPA, while Chinese women show slower elimination and higher blood levels of NET-EN. Extensive studies of new synthetic esters of levonorgestrel have proceeded to Phase II clinical trials with levonorgestrel butanoate. This ester is an effective contraceptive for 3 months at 12.5 mg, or 5-6 months at a dose of 25 or 50 mg. Trials of combined estrogen and progestogen injectables once-monthly have been ongoing for 10 years. The ratio of the 2 components is as important as the amounts. 2328 women from 12 countries participated in trials of DMPA 25 mg-estradiol cypionate 5 mg, and NET-EN 50 mg-estradiol valerate 5 mg. The continuation rate was better than that for 3-monthly progestogen-only injectables, because of less irregular bleeding. A combined injectable called Cyclofem, DMPA 25 mg-estradiol cypionate is being introduced in several countries. The steadily increasing demand for long-acting injectables prompts development of better formulations.
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PMID:Long-acting hormonal contraceptives for women. 195 67

Several processes participate in the clearance of atrial natriuretic peptide (ANP) from the circulation, one of which is enzymatic degradation. Endoprotease EC 3.4.24.11 (NEP 24.11), present within the kidney in high concentration, has been shown in vitro to degrade ANP. Phosphoramidon and thiorphan, two potent NEP 24.11 inhibitors, have been shown to prevent the enzymatic degradation of ANP. The purpose of the present study was to determine if phosphoramidon or thiorphan would alter the in vivo time course of the pharmacologic effects of ANP. The magnitude and duration of the ANP-induced increase in urine output and sodium and cyclic GMP excretion were examined with and without either thiorphan or phosphoramidon. Six separate groups of anesthetized rats received either a low, medium, or high infusion rate of thiorphan or phosphoramidon. Renal responses to ANP were potentiated and prolonged during the low phosphoramidon infusion (3 Ki) and the medium thiorphan infusion (150 Ki). At high inhibitor infusion rates in the anesthetized rat, ANP elicited a marked depressor response. In the conscious spontaneously hypertensive rat (SHR), a 15-min intravenous (i.v.) infusion of ANP (1 microgram/kg/min) lowered mean arterial pressure (MAP 23 +/- 6 mm Hg), with an approximately 35-min duration of action. A simultaneous i.v. infusion of phosphoramidon (high dose) produced both a potentiation (33 +/- 3 mm Hg) and a prolongation (greater than 65 min to return to baseline) of the depressor response. These data lend support to the hypothesis that enzymatic breakdown of ANP may play an important role in regulating the actions of atrial natriuretic peptide.
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PMID:Degradation of atrial natriuretic peptide: pharmacologic effects of protease EC 24.11 inhibition. 247 3

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.
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PMID:Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin. 252 62

The most effective, convenient, reversible method of birth control is considered to be long-acting progestogen injections. Used by over 90 countries, Depot medroxy-progesterone acetate (DMPA, Depo-Provera, Upjohn) has yet to be approved by the U.S. Food and Drug Administration. The reluctance of the FDA to approve DMPA and much of the controversy surrounding this method revolve around the results of testing done on animals who were given large doses of the progestogen over a long period of time and developed tumors. However, the large body of research and records on this method that have been compiled over the past 30 years is positive. The injectable method works like oral contraceptives, inhibiting ovulation. Changes in menstruation have been the chief complaint of women who use this method; however, the duration and frequency of spotting and bleeding diminish over time. Other side effects of DMPA and Norethindrone enanthate (NET EN, Noristerat, Schering) are discussed. Also discussed is the history of development and testing for the 2 methods and subdermal implants, specifically Norplant.
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PMID:Injectable contraception. 252 77

The aim of this study was to investigate the effects of estradiol and tamoxifen (TAM) on the growth of human endometrial carcinomas in athymic mice. Tissues from primary tumors were implanted into estradiol-treated mice. In passage 2, animals were treated with (a) placebo, (b) estradiol, (c) estradiol plus TAM, and (d) TAM alone. The size of the tumors was measured weekly. Estrogen receptors (ER) were determined with the dextran-coated charcoal method and/or ER enzyme-linked immunoassay. Progesterone receptors were measured with the dextran-coated charcoal technique. Of 16 primary tumors, 2 grew in the athymic mice and were studied further. Tumor EL was positive for ER (145 fmol/mg protein) and progesterone receptors (993 fmol/mg protein). Tumor EL in passage 2 was not significantly stimulated by estradiol, but was stimulated by a combination of estradiol and TAM. Treatments (estradiol, estradiol plus TAM, or TAM) all increased tumor growth in passage 3. Tumor BR and a metastasis BR-MET were ER and progesterone receptor negative, applying dextran-coated charcoal, ER enzyme-linked immunoassay, and immunocytochemistry. The BR and BR-MET cells contain the complete ER gene but do not express any measurable amounts of ER mRNA as quantitated by Northern blot analysis, using a complete ER complementary DNA probe. In all animal passages the growth rate was significantly higher in estradiol-treated mice compared with the control. TAM alone had some growth stimulatory effect, but much smaller than observed in the estradiol group. TAM inhibited estradiol-stimulated growth. These results suggest that estradiol and possibly TAM are capable of stimulating tumor growth in the athymic mice independently from ER, potentially through a host-mediated mechanism.
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PMID:Enhanced growth of an estrogen receptor-negative endometrial adenocarcinoma by estradiol in athymic mice. 275 9

The site of gonadotrophin inhibition in long-term users of injectable contraceptives is still debatable. The pituitary response to LHRH (50 micrograms, I.V.) was assessed in 32 women. Sixteen cases were using either medroxyprogesterone acetate (DMPA; n = 8 150 mg I.M. every three months) or norethisterone enanthate (NET-EN; n = 8, 200 mg every 2 months) for at least 18 months. The remaining cases (n = 16) were normal fertile females not using any hormonal contraceptive (control group). The pituitary response to LHRH injection in both injectable subgroups was nearly identical to that in the control group. Neither the basal levels nor the net increase in gonadotrophins following LHRH injection were significantly different in the study groups from those of the control group. Long-term use of DMPA or NET-EN does not affect the pituitary responsiveness to LHRH injection and the pituitary is not a primary site for ovulation inhibition in these cases.
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PMID:Pituitary response to LHRH in long-term users of injectable contraceptives. 295 67


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