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Progesterone regulation of vascular thromboxane A(2) receptors in rhesus monkeys.

Minshall RD, Pavcnik D, Halushka PV, Hermsmeyer K.

Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA.

We hypothesized that progesterone regulates thromboxane A(2) receptor (TxA(2)R) density in primate vascular muscle and that TxA(2)R density correlates with coronary reactivity in vivo and in vitro. Reactivity to serotonin + U-46619 was determined by angiography in surgically postmenopausal [ovariectomized (Ovx)] rhesus monkeys without progesterone replacement and after 2-wk progesterone treatment (1-2 ng/ml). In untreated Ovx animals, 100 micromol/l serotonin + 1 micromol/l U-46619 (syringe concentrations) provoked vasospasm-like constrictions in six of six monkeys; zero of six progesterone-treated monkeys developed vasospasms. Sustained Ca(2+) responses in vascular muscle cells isolated from Ovx coronaries (208 +/- 63% of basal 20 min after stimulation) treated with serotonin + U-46619 contrasted with transient Ca(2+) responses (143 +/- 18% of basal and decreasing 5 min after stimulation) in progesterone-treated monkeys. The maximum density of [1S-(1I,2J(5Z),3I(1E,3R*),4I)]-7-[3-(3-hydroxy-4-(4'-[(125)I]iodophenoxy)- 1-butenyl)-7-oxabicyclo[2.2.1]heptan-2-yl]-5-heptenoic acid ([(125)I]-BOP) binding was greater (P < 0.01) in carotid arteries and aortic membranes from Ovx (109 +/- 11 fmol/mg) compared with progesterone-treated (43 +/- 15 fmol/mg) monkeys. TxA(2)R immunolabeling revealed greater coronary TxA(2)R labeling in Ovx compared with progesterone-treated monkeys. The results suggest that progesterone can decrease arterial TxA(2)R in Ovx monkeys.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11557538&dopt=Abstract progesterone, progesterone cream



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Progesterone-induced secretion of growth hormone, insulin-like growth factor I and prolactin by human breast cancer explants.

Gregoraszczuk EL, Milewicz T, Kolodziejczyk J, Krzysiek J, Basta A, Sztefko K, Kurek S, Stachura J.

Laboratory of Reproductive Physiology and Toxicology of Domestic Animals, Department of Physiology, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-060 Krakow, Poland.

The aim of the study was to evaluate the potential of human breast cancer tissue to secrete growth hormone (GH), insulin-like growth factor I (IGF-I) and prolactin in response to 10(-7) M progesterone stimulation. Explants were divided according to estrogen receptor (ER)/progesterone receptor (PR) phenotype (ER(-)PR(-); ER(+)PR(-); ER(+)PR(+); ER(-)PR(+)). Our results show distinct differences in cultured breast cancer tissue responses to progesterone stimulation with regard to secretion of proliferative agents such as GH, IGF-I and prolactin. All but ER(-)PR(-) breast cancer cell types responded in vitro to progesterone stimulation with an increase in local GH secretion, while in non-malignant tissue progesterone induced local GH secretion only in PR(+) cells. Moreover, only in PR(+) cells did progesterone stimulate local IGF-I and prolactin secretion, in both malignant and non-malignant tissue. This study provides evidence for the first time that in PR(+) breast cancer tissue, progesterone may increase GH, prolactin and IGF-I secretion in both malignant and surrounding non-malignant tissue. These hormones may act as local growth factors that stimulate the proliferation of mammary tumors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11560097&dopt=Abstract progesterone, progesterone cream



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Serum progesterone levels correlate with decreased cerebral edema after traumatic brain injury in male rats.

Wright DW, Bauer ME, Hoffman SW, Stein DG.

Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. dwwrigh emory.edu

Previous animal research suggests that progesterone may have powerful neuroprotective effects in traumatic brain injury (TBI). This experiment tested the hypothesis that progesterone levels correlate with decreased cerebral edema in male rats with bilateral medial frontal cortex injuries. Three groups of male Sprague-Dawley rats were used: injured given progesterone (4 mg/kg), injured given vehicle (oil), and uninjured controls given vehicle. Progesterone or vehicle was administered intraperitoneally at 1, 6, and 24 h postinjury. At 48 h postinjury, the rats were killed, brains extracted, and assayed for edema. Percent difference in water content of the area surrounding the lesion was compared to posterior cortex. A strong inverse relationship was found between serum progesterone levels and percent cerebral edema; the higher the progesterone levels, the lower the percent edema. Both progesterone and oil-treated animals had some edema compared to sham-operated controls. The brains of the injured animals given control solution were higher in water content than either the uninjured group or injured progesterone-treated rats 48 h postinjury. These findings confirm that progesterone significantly decreases cerebral edema after TBI in adult male subjects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11565602&dopt=Abstract progesterone, progesterone cream



progesterone cream
Luteal expression of cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase, and 20alpha-hydroxysteroid dehydrogenase genes in late pregnant rats: effect of luteinizing hormone and RU486.

Stocco CO, Chedrese J, Deis RP.

Laboratorio de Reproduccion y Lactancia, CONICET, 5500 Mendoza, Argentina. costocco uic.edu

A decrease in serum progesterone at the end of pregnancy is essential for the induction of parturition in rats. We have previously demonstrated that LH participates in this process through: 1) inhibiting 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity and 2) stimulating progesterone catabolism by inducing 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) activity. The objective of this investigation was to determine the effect of LH and progesterone on the luteal expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450(scc)), 3beta-HSD, and 20alpha-HSD genes. Gene expression was analyzed by Northern blot analysis 24 and 48 h after administration of LH or vehicle on Day 19 of pregnancy. StAR and 3beta-HSD mRNA levels were lower in LH-treated rats than in rats administered with vehicle at both time points studied. P450(scc) mRNA levels were unaffected by LH. The 20alpha-HSD mRNA levels were not different between LH and control rats 24 h after treatment; however, greater expression of 20alpha-HSD, with respect to controls, was observed in LH-treated rats 48 h after treatment. Luteal progesterone content dropped in LH-treated rats at both time points studied, whereas serum progesterone decreased after 48 h only. In a second set of experiments, the anti-progesterone RU486 was injected intrabursally on Day 20 of pregnancy. RU486 had no effect on 3beta-HSD or P450(scc) expression but increased 20alpha-HSD mRNA levels after 8 h treatment. In conclusion, the luteolytic effect of LH is mediated by a drop in StAR and 3beta-HSD expression without effect on P450(scc) expression. We also provide the first in vivo evidence indicating that a decrease in luteal progesterone content may be an essential step toward the induction of 20alpha-HSD expression at the end of pregnancy in rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11566732&dopt=Abstract progesterone, progesterone cream



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Reduced binding of progesterone receptor to its nuclear response element after human labor onset.

Henderson D, Wilson T.

Department of Obstetrics and Gynaecology, Dundee University and Medical School, Scotland.

OBJECTIVE: There is indirect evidence of decreased progesterone-activated transcription after human labor onset. Binding of the progesterone receptor to its response element is a prerequisite of progesterone-activated transcription. We established an assay to investigate whether there is reduced binding of progesterone receptor to its nuclear response element after, compared with before, labor onset. STUDY DESIGN: The binding of progesterone receptor from the decidua to its nuclear response element was measured in gel shift assays. Tissues from 52 patients who were term, preterm, in labor, and not in labor were compared. RESULTS: A 9-fold decrease in progesterone receptor binding to its response element was observed in tissues obtained after, compared with before, the onset of labor (P = .0008). In both preterm and term not-in-labor tissues, binding was higher than for in-labor tissues (P = .0172 for preterm; P = .0147 for term, Mann-Whitney U test). CONCLUSION: These findings provide a mechanism for the effective withdrawal of progesterone in human parturition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11568781&dopt=Abstract progesterone, progesterone cream



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Delayed effect of low progesterone concentrations on bovine uterine PGF(2alpha) secretion in the subsequent oestrous cycle.

Shaham-Albalancy A, Folman Y, Kaim M, Rosenberg M, Wolfenson D.

Department of Animal Science, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel.

Low progesterone concentrations during the bovine oestrous cycle induce enhanced responsiveness to oxytocin challenge late in the luteal phase of the same cycle. The delayed effect of low progesterone concentrations during one oestrous cycle on uterine PGF(2alpha) secretion after oxytocin challenge on day 15 or 16 of the subsequent cycle was studied by measuring the concentrations of the major PGF(2alpha) metabolite (13,14-dihydro-15-keto PGF(2alpha); PGFM) in plasma. Two experiments were conducted, differing in the type of progesterone treatment and in the shape of the low progesterone concentration curves. In Expt 1, progesterone supplementation with intravaginal progesterone inserts, with or without an active corpus luteum, was used to obtain high, or low and constant plasma progesterone concentrations, respectively. In Expt 2, untreated cows, representing high progesterone treatment, were compared with cows that had low but increasing plasma progesterone concentrations that were achieved by manipulating endogenous progesterone secretion of the corpus luteum. Neither experiment revealed any differences in plasma progesterone concentrations between the high and low progesterone groups in the subsequent oestrous cycle. In both experiments, both groups had similar basal concentrations of PGFM on day 15 (Expt 1) or 16 (Expt 2) of the subsequent oestrous cycle, 18 days after progesterone treatments had ended. In both experiments, the increases in PGFM concentrations in the low progesterone groups after an oxytocin challenge were markedly higher than in the high progesterone groups. These results indicate that low progesterone concentrations during an oestrous cycle have a delayed stimulatory effect on uterine responsiveness to oxytocin during the late luteal phase of the subsequent cycle. This resulting increase in PGF(2alpha) secretion may interfere with luteal maintenance during the early stages of pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11570971&dopt=Abstract progesterone, progesterone cream



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Different role of endothelium/nitric oxide in 17beta-estradiol- and progesterone-induced relaxation in rat arteries.

Chan HY, Yao X, Tsang SY, Chan FL, Lau CW, Huang Y.

Department of Physiology, Chinese University of Hong Kong, People's Republic of China.

The present study was aimed to examine the different role of endothelium/nitric oxide in relaxation induced by two female sex hormones, 17beta-estradiol and progesterone in rat isolated aortas and mesenteric arteries. The isometric force of each ring was measured with Grass force-displacement transducers in the organ bathes. 17beta-Estradiol induced both endothelium-dependent and -independent relaxation in the rat aortas but only the endothelium-independent relaxation in the rat mesenteric arteries. In contrast. progesterone induced both endothelium-dependent and -independent relaxation in the rat mesenteric arteries but only endothelium-independent relaxation in rat aortas. N(G)-Nitro-L-arginine methyl ester and methylene blue attenuated the relaxant response to 17beta-estradiol in the aortic rings or to progesterone in the mesenteric arteries. Pretreatment with L-arginine antagonized the effect of N(G)-nitro-L-arginine methyl ester on sex hormone-induced relaxation. The endothelium contribution to relaxation seems to only relate to lower concentrations of 17beta-estradiol and progesterone. In summary, the present results clearly demonstrate a different role of the functional endothelium in the relaxant response to 17beta-estradiol or progesterone in the conduit vessel (aorta) and the resistance vessels (mesenteric artery). Nitric oxide contributes largely to the endothelium-dependent relaxation induced by 17beta-estradiol in the isolated aortas or by progesterone in the mesenteric arteries.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11589501&dopt=Abstract progesterone, progesterone cream