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[Value of serum progesterone for ectopic pregnancy in therapeutic effect monitoring]

[Article in Chinese]

Fan JT, Long FY.

Department of Gynecology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.

OBJECTIVE: To study the value of serum progesterone in selecting the candidate patients with ectopic pregnancy (EP) for methotrexate (MTX) treatment and in monitoring the effect of the treatment. METHODS: Thirty-seven EP patients who were given single-dose intramuscular injection with 50 mg/m2 MTX were divided into success and failure groups according to the effect of the treatment. The serum progesterone concentrations in these patients were measured and compared between the 2 groups, and the receiver-operator curves (ROC) were used to determine the critical serum progesterone levels for assessing the effect of MTX treatment. The time consumed respectively by serum progesterone and beta-human chorionic gonadotrophin (beta-hCG) decreasing to below normal level was also compared. RESULTS: The serum progesterone concentrations of the success group (7.93+/-2.02 ng/ml) were significantly lower than those of the failure group (14.53+/-1.72 ng/ml, P<0.05). The recommended critical level for assessing the effect of MTX treatment for EP patients was 11 ng/ml according to the ROC, and the time for serum progesterone decreasing to below normal level was significantly less than that for beta-hCG. CONCLUSION: Serum progesterone can be used as an index for selecting candidate EP patients for MTX treatment, and also as a good indicator for assessing the therapeutic effect after treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12581973&dopt=Abstract progesterone, progesterone cream



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The transfection-induced overexpression of IGF-binding protein-4 affects the secretory activity of porcine ovarian granulosa cells and their response to hormones and IGF-I.

Sirotkin AV, Makarevich AV, Corkins MR, Kotwica J, Bulla J.

Research Institute of Animal Production, 949 92 Nitra, Slovakia. sirotkin vuzv.sk

The aim of our studies was to examine whether IGF-binding protein (IGFBP)-4 is involved in the control of the secretion of various ovarian substances and also the mediation of the effects of several hormones and growth factors on this secretion. For this purpose, we carried out the transfection of porcine granulosa cells with a cDNA sense construct, increasing IGFBP-4 synthesis. We then compared the release of IGFBP-3, progesterone, oxytocin and IGF-I by control and transfected cells cultured with and without porcine LH (100 ng/ml), porcine GH (100 ng/ml), IGF-I (10 ng/ml), oxytocin (10 ng/ml) and estradiol-17beta (100 ng/ml). The concentration of IGFBP-4 produced was assessed using ligand blotting, and the release of progesterone, oxytocin, IGF-I and IGFBP-3 was evaluated using RIA/IRMA techniques. It was observed that GH, IGF-I, estradiol, LH and oxytocin alter the progesterone, oxytocin, IGF-I and IGFBP-3 release by porcine ovarian granulosa cells. Transfection of these cells with an IBFBP-4 cDNA expression construct significantly increased the IGFBP-4 accumulation in cell-conditioned medium. Furthermore, this transfection significantly reduced progesterone, oxytocin and IGFBP-3 release, and increased IGF-I output in cells cultured in the absence or presence of GH, IGF-I, estradiol and LH. The addition of oxytocin, but not of other tested substances, fully or partially prevented the effects of IGFBP-4 overexpression on IGFBP-3, IGF-I, but not on progesterone release. The present results suggested that IGFBP-4, as well as GH, IGF-I, estradiol, LH and oxytocin, is a potent regulator of porcine ovarian steroid (progesterone), nonapeptide hormone (oxytocin), growth factor (IGF-I) and growth factor-binding protein (IGFBP-3) release. IGFBP-4 is an inhibitor of basal progesterone, oxytocin and IGFBP-3 release and a stimulator of IGF-I output by porcine ovarian cells. The action of IGFBP-4 on the ovary can be mediated by (1) inhibition of oxytocin release, (2) suppression of receptor/postreceptor events induced by other hormones and IGF-I and (3) stimulation of IGF-I release.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11357060&dopt=Abstract progesterone, progesterone cream



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Microbial transformations of steroids--XII. Progesterone hydroxylation profiles are modulated by post-translational modification of an electron transfer protein in Streptomyces roseochromogenes.

Berrie JR, Williams RA, Smith KE.

Molecular and Cellular Biology, Division of Biomedical Sciences, Queen Mary and Westfield College Medical School, University of London, Mile End Road, London E1 4NS, UK.

When Streptomyces roseochromogenes strain 10984 was incubated with exogenous progesterone for 25 h the major monohydroxylated metabolite, 16alpha-hydroxyprogesterone was produced in 3.6 fold excess to the minor metabolite 2beta,16alpha-dihydroxyprogesterone. In a reconstituted system containing highly purified progesterone 16alpha-hydroxylase cytochrome P-450, and electron transfer proteins ferredoxin-like redoxin (roseoredoxin) and redoxin reductase (roseoredoxin reductase), both metabolites were produced but in a 10:1 ratio. When S. roseochromogenes was pre-incubated for 8 h with 0.32 mM progesterone and the purified components of the hydroxylase system incubated as before, the ratio of 16alpha-hydroxyprogesterone to 2beta,16alpha-dihydroxyprogesterone produced decreased to 2.8:1, virtually identical to the ratio in whole cell transformations. Reconstitution assays containing all combinations of hydroxylase proteins purified from progesterone pre-incubated and control cells showed that the roseoredoxin was solely responsible for the observed changes in in vitro metabolite ratios. The fact that the lower 16alpha-hydroxyprogesterone to 2beta,16alpha-dihydroxyprogesterone ratio was also obtained when S. roseochromogenes was exposed to 0.335 mM cycloheximide for 8 h prior to the progesterone pre-incubation, pointed to post-translation modification of the roseoredoxin. Separation of two isoforms of roseoredoxin by isoelectric focusing supported this proposition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11358678&dopt=Abstract progesterone, progesterone cream



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Increased depot medroxyprogesterone acetate use increases family planning program pharmaceutical supply costs.

Margulies R, Miller L.

University of Washington School of Medicine, Seattle, WA, USA.

To measure the use rates of depot medroxyprogesterone acetate and oral contraceptives and compare the costs between the two methods to see whether these trends had impacted the pharmaceutical acquisition costs for a family planning program, we compared vendor invoice costs over three time periods, 1992, 1994, and 1999. Visit types and client demographic statistics were tabulated from existing encounter record data sources. A local pharmaceutical chain was queried about their acquisition costs for similar products. Since 1992, depot medroxyprogesterone acetate use has increased from 3 to 17% while oral contraceptive use has decreased from 45 to 40% of contraceptive clients. The cost to our program for depot medroxyprogesterone acetate is $4.75 for 28 days and the average pill package is purchased for $1.35. The cost to our program is 4 times greater for the injection contraceptive user than for the oral contraceptive user. Approximately 80% of our clients have household incomes less than 200% of the poverty level and obtain their services from our program for free. This combination of increasing popularity and the high cost of depot medroxyprogesterone acetate has resulted in a great increase in the pharmacy acquisition cost. The oral contraceptive manufacturers make their products available at large discounts (20-fold reduction), but depot medroxyprogesterone acetate is not provided at a similar discount (2.8-fold reduction). We believe this is because there is no generic or competing product. The high cost of depot medroxyprogesterone acetate could jeopardize our ability to offer this highly effective method of birth control to all women.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11368987&dopt=Abstract progesterone, progesterone cream



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Progesterone stimulates Krox-20 gene expression in Schwann cells.

Guennoun R, Benmessahel Y, Delespierre B, Gouezou M, Rajkowski KM, Baulieu EE, Schumacher M.

INSERM U488, 80, rue du General Leclerc, 94276, Bicetre, France. guennoun kb.inserm.fr

The gene of the zinc finger transcription factor Krox-20 (Egr-2) is expressed in Schwann cells and plays an important role in myelination of peripheral nerves. We have shown that progesterone promotes myelination in the regenerating sciatic nerve and in cocultures of Schwann cells and sensory neurones. To determine whether progesterone regulates Krox-20 expression, we measured its effects on Krox-20 mRNA levels in the MSC80 mouse Schwann cell line by semi-quantitative RT-PCR. Although low levels of Krox-20 mRNA are detectable in MSC80 cells cultured in defined medium, treatment with 10(-6) M progesterone induces a rapid (15 min) and transient increase in the levels of Krox-20 mRNA. Lower doses of progesterone (10(-9), 10(-8) and 10(-7) M) are also effective in increasing Krox-20 mRNA. Other steroids including testosterone, dexamethasone, and estradiol are ineffective when added to the culture medium at 10(-6) M for 1 h. The induction of Krox-20 mRNA was also observed with the selective progesterone agonist Organon 2058 and was abolished by treating the MSC80 Schwann cells with the progesterone antagonist RU486, indicating that progesterone induces Krox-20 mRNA expression by binding to its intracellular receptor. The induction of Krox-20 by progesterone was also demonstrated in primary cultures of Schwann cells isolated from neonatal rat sciatic nerves, at the mRNA level by RT-PCR and at the protein level by immunohistochemistry. As Krox-20 is a necessary step for the initiation of myelin formation in peripheral nerves, its stimulation by progesterone suggests an important signalling function for this steroid in myelination.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11376858&dopt=Abstract progesterone, progesterone cream



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Effect of exogenous ovine placental lactogen on basal and prostaglandin-stimulated progesterone production by porcine luteal cells.

Gregoraszczuk EL, Gertler A, Futoma E.

Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-060 Cracow, Poland. greg zuk.iz.uj.edu.pl

The ability of ovine placental lactogen (oPL) to stimulate progesterone secretion of porcine luteal cells isolated from ovaries in different stages of the oestrous cycle and to support the luteotropic action of PGE2 or to protect the corpus luteum (CL) against the luteolytic action of PGF2 alpha was investigated. oPL in all doses used had no effect on progesterone production of cells isolated from early developing corpora lutea while in doses of 1 and 10 ng/ml it increased oestradiol secretion by this type of cells. In doses of 1, 10 and 100 ng/ml it also increased progesterone secretion of cells isolated from mature corpora lutea in a dose-dependent manner. No influence on progesterone production of cells isolated from regressing corpora lutea was observed. oPL added to the culture media had no effect on PGE2-stimulated progesterone production by cells isolated from mature corpora lutea. However, it exerted a protective effect against the luteolytic action of PGF2 alpha observed in cultures treated with PGF2 alpha alone or in combination with PGE2 in a ratio of 4:1. These studies provide evidence that oPL is luteotropic and supports progesterone production in swine. The fact that oPL acted directly on ovarian steroidogenesis suggests that it may also play some role under non-pregnant physiological conditions. Future studies of structural and functional proteins secreted by the porcine conceptus will help resolve this uncertainty.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11402703&dopt=Abstract progesterone, progesterone cream



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Progesterone treatment that either blocks or augments the estradiol-induced gonadotropin-releasing hormone surge is associated with different patterns of hypothalamic neural activation.

Richter TA, Robinson JE, Evans NP.

Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, UK.

Progesterone can either augment or inhibit the surge of gonadotropin-releasing hormone (GnRH) that drives the preovulatory luteinizing hormone (LH) surge. This study investigated the central mechanisms through which progesterone might achieve these divergent effects by examining the effects of exogenous steroids on the activation of GnRH neurons and non-GnRH-immunopositive cells in the preoptic area/anterior hypothalamus of steroid-treated ovariectomized ewes. Fos expression (an index of cellular activation) was examined during the estradiol-induced GnRH surge in ewes treated with progesterone using regimes that have been reported to either augment (progesterone pretreatment) or inhibit (progesterone treatment at the time of the surge-inducing estradiol increment) the GnRH surge. Control groups received either no progesterone pretreatment or no surge-inducing estradiol increment. Induction of an LH surge was associated with a significant (p < 0.0001) increase in the proportion of activated GnRH neurons, irrespective of whether ewes received progesterone pretreatment. However, the number of non-GnRH-immunopositive cells activated during the surge was significantly (p < 0.0001) increased in ewes that received the progesterone pretreatment. By contrast, the proportion of GnRH neurons and non-GnRH-immunopositive cells that expressed Fos was significantly (p < 0.0001) reduced in ewes in which the surge was inhibited by progesterone compared to ewes in which a surge was stimulated. These data indicate that (1) progesterone pretreatment increases the activation of non-GnRH cells during the estradiol-induced surge, but does not affect the proportion of GnRH neurons activated and (2) when administered concurrently with a surge-inducing estradiol increment, progesterone prevents the activation of GnRH neurons and non-GnRH cells that is normally associated with the estradiol-induced surge. Therefore, progesterone does not appear to augment the GnRH surge by increasing the proportion of GnRH neurons that are activated by estradiol, whereas inhibition of the GnRH surge involves prevention of the activation of GnRH neurons. Thus, the augmentation and inhibition of the GnRH surge by progesterone appear to be regulated via different effects on the GnRH neurosecretory system.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11408779&dopt=Abstract progesterone, progesterone cream