progesterone cream
Sufficient Progesterone-priming Prior to Estradiol Stimulation Is Required for Optimal Induction of the Cervical Prostaglandin System in Pregnant Sheep at 0.7 Gestations.

Wu WX, Coksaygan T, Chakrabarty K, Collins V, Rose JC, Nathanielsz PW.

The purposes of this study were to determine the separate and interactive functions of progesterone and estradiol in regulating the cervical prostaglandin (PG) system in pregnant sheep at 0.7 gestations. At 106-108 days of gestational age (dGA), ewes were treated with vehicle for 14 days (n=5), or vehicle for 12 days followed by estradiol 5 mg twice a day, intramuscularly for 2 days (n=5) or progesterone 100 mg, twice a day, intramuscularly for 14 days (n=5) or progesterone 100 mg twice a day, intramuscularly for 10 days and then 2 days vehicle followed by estradiol 5 mg twice a day intramuscularly for 2 days (n=5). At 121-123 dGA cervical tissues were obtained under halothane anesthesia. Cervical RNA and protein were extracted and analyzed for prostaglandin-endoperoxide synthase 2 (COX2), two PGE2 receptors, PTGER2 and PTGER4, and estrogen receptor alpha (ESR1) by Northern and Western blot analysis. Immunocytochemistry and in situ hybridization were applied to localize cellular distribution of COX2, PTGER2 and PTGER4 in the cervix. Data were analyzed by Anova. COX2 and PTGER4 mRNAs and proteins were increased (P<0.05) in ewes treated with combined estradiol and progesterone, but not in ewes treated with estradiol or progesterone alone compared with controls. ESR1 mRNA was increased in ewes treated with progesterone and estradiol plus progesterone. In contrast, PTGER2 mRNA and protein remained the same after all treatments. COX2 mRNA and protein were only localized in cervical glandular epithelial cells, whereas PTGER2 and PTGER4 were localized in both cervical glandular epithelial and smooth muscle cells. In conclusions: These data suggest that additional progesterone priming at 0.7 gestations synergizes with estradiol to induce cervical COX2, PTGER4 and ESR1 and support our hypothesis that stimulation of the cervical PG system by estradiol is optimized by sufficient progesterone priming in the pregnant sheep cervix.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15829624&dopt=Abstract progesterone, progesterone cream



progesterone cream
Regulation of progesterone production in human term trophoblasts in vitro by CRH, ACTH and cortisol (prednisolone).

Jeschke U, Mylonas I, Richter DU, Hocker I, Briese V, Makrigiannakis A, Friese K.

1st Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University of Munich, Maistrasse 11, 80337, Munich, Germany, udo.jeschke med.uni-muenchen.de.

Background: In most mammals, onset of labor is accompanied with progesterone withdrawal. In humans, cortisol blockade of progesterone is a possible mechanism involved in the initiation of labor. Therefore, aim of the study was to clarify the effect of CRH, ACTH and cortisol (prednisolone) on the release of progesterone by term trophoblast cells in vitro. Methods: Cytotrophoblast cells were prepared from human term placentas by standard dispersion of villous tissue followed by a percoll gradient centrifugation step. Trophoblasts were incubated with CRH, ACTH as well as with prednisolone Results: The release of progesterone is decreased in CRH- and ACTH-treated trophoblast cell cultures compared to untreated trophoblast cells. Addition of prednisolone in varying concentrations leads to an increase of trophoblast progesterone production. Conclusions: The results suggest that CRH and ACTH directly modulate the endocrine function of trophoblasts in culture by downregulating progesterone production. Prednisolone on the other hand showed a stimulating effect on progesterone production in term trophoblast cells in vitro. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that CRH and ACTH are directly involved in the auto- or paracrine regulation of this procedure.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15834733&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone represses interleukin-8 and cyclo-oxygenase-2 in human lower segment fibroblast cells and amnion epithelial cells.

Loudon JA, Elliott CL, Hills F, Bennett PR.

Imperial College Parturition Research Group, Wolfson and Weston Centre for Family Health, Institute of Reproductive and Developmental Biology, London W12 0HN, United Kingdom. j.loudon ic.ac.uk

Labor is preceded by cervical ripening through upregulation of interleukin (IL)-1beta, IL-8, and increased prostaglandin synthesis via inducible type 2 cyclooxygenase (COX-2). Progesterone maintains myometrial quiescence during pregnancy. In this study, we examined the effects of IL-1beta and progesterone on IL-8 and prostaglandin E2 (PGE2) synthesis and IL-8 and COX-2 mRNA and promoter activity in amnion cells and lower segment fibroblast (LSF) cells. In both cell types, progesterone had no effect on basal IL-8 or PGE2 synthesis. In LSF cells, IL-1beta significantly increased IL-8 and PGE2 synthesis and COX-2 and IL-8 mRNA expression, but progesterone significantly attenuated these effects. In prelabor amnion cells, IL-1beta also increased IL-8 and PGE2 synthesis and both COX-2 and IL-8 mRNA and promoter expression; however, progesterone significantly attenuated these effects on IL-8 and PGE2 synthesis and COX-2 expression. In postlabor amnion cells, IL-1beta increased IL-8 and PGE2 synthesis and COX-2 expression, but progesterone did not attenuate the effect of IL-1beta upon IL-8 synthesis. Progesterone repression of IL-8 and COX-2 in LSF cells suggests that IL-8 and COX-2 have similar regulatory mechanisms in LSF cells and that progesterone may play a role in maintenance of cervical competence. The lack of effect of progesterone on IL-8 in postlabor cells may be the result of downregulation of the progesterone receptor during labor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12672669&dopt=Abstract progesterone, progesterone cream



progesterone cream
Withdrawal from progesterone increases expression of alpha4, beta1, and delta GABA(A) receptor subunits in neurons in the periaqueductal gray matter in female Wistar rats.

Griffiths J, Lovick T.

Department of Physiology, University of Birmingham, Birmingham B15 2TT, United Kingdom.

Premenstrual dysphoric disorder (PMDD) shows comorbidity with other psychiatric conditions such as panic disorder (PD). The symptoms of both conditions are exacerbated during the late luteal phase of the menstrual cycle, when progesterone levels fall sharply. The present study investigated the effect of withdrawal from progesterone (PWD) on expression of alpha4, beta1, and delta GABA(A) receptor subunits in neurons within the panic circuitry of the midbrain periaqueductal gray matter (PAG) in adult female Wistar rats. Immunostaining for alpha4, beta1, and delta GABA(A) receptor subunits was present in neurons throughout the PAG in vehicle-treated animals (VEH), in rats after 24 hours withdrawal from a progesterone dosing regime (PWD, 5 mg kg(-1) i.p. twice daily for 6 days), and in animals maintained on progesterone for 7 days (HP). Compared to HP and VEH animals, which did not differ significantly from each other, the number of immunostained neurons present in the PAG of PWD rats was significantly higher. The effect was most pronounced in the dorsolateral column of the PAG. The parallel changes in the three GABA(A) receptor subunits suggests that falling progesterone levels may be associated with expression of new receptors of the alpha4beta1delta subtype. This could lead to functional changes in GABAergic transmission within the PAG. We suggest that changes in GABA(A) receptor-mediated inhibitory tone in the PAG consequent to withdrawal from progesterone may contribute to the increased anxiety and susceptibility to panic seen during the late luteal phase of the menstrual cycle in PMDD and PD patients. J. Comp. Neurol. 486:89-97, 2005. (c) 2005 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15834956&dopt=Abstract progesterone, progesterone cream



progesterone cream
The neuroprotective effect of progesterone after traumatic brain injury in male mice is independent of both the inflammatory response and growth factor expression.

Jones NC, Constantin D, Prior MJ, Morris PG, Marsden CA, Murphy S.

Institute of Cell Signalling, University of Nottingham, Clifton Blvd., Nottingham NG7 2UH, UK.

Previous studies suggest that progesterone may possess neuroprotective properties after traumatic insult but, with the exception of reduced formation of cerebral oedema, limited experimental evidence has been presented to support this claim. In the present study we focused on the effect of progesterone treatment on structural and functional deficits in an experimental model of traumatic brain injury. Female mice exhibited significantly (P = 0.0445) reduced lesion volumes compared with males after aseptic cryogenic cerebral injury (ACI), suggesting that female sex steroids provide protection against this injury. In male mice, progesterone treatment after injury (three intraperitoneal doses of 8 mg/kg) reduced lesion volume (P = 0.0429) and improved performance in a spatial cognitive task (Morris water maze; P = 0.0014). However, progesterone had no demonstrable effect on the formation of oedema as measured using T2-weighted magnetic resonance imaging, nor did it affect brain water content. The pro-inflammatory cytokines TNF-alpha and IL-1beta, and growth factors BDNF and G-CSF, were all strongly transcriptionally activated after ACI. However, progesterone administration did not affect expression of these genes. This study provides strong evidence that progesterone possesses neuroprotective properties in a mouse model of traumatic brain injury, but suggests that the steroid achieves this effect through mechanism(s) independent of the inflammatory response or growth factor up-regulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15845082&dopt=Abstract progesterone, progesterone cream



progesterone cream
Immunoreactivity for c-kit and p63 as an adjunct in the diagnosis of adenoid cystic carcinoma of the breast.

Mastropasqua MG, Maiorano E, Pruneri G, Orvieto E, Mazzarol G, Vento AR, Viale G.

1Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan, School of Medicine, Milan, Italy.

Adenoid cystic carcinoma of the breast represents a unique clinicopathologic entity with a variable histological appearance and a relatively indolent clinical course in most of the cases. Adenoid cystic carcinoma may be difficult to differentiate from infiltrating duct carcinomas, and in particular from tubular and cribriform carcinomas, especially in core or vacuum-assisted biopsies. We evaluated the prevalence of c-kit, p63, and e-cadherin immunoreactivity in a series of 20 adenoid cystic carcinomas, comparing the results with those obtained in a series of infiltrating tubular carcinomas and infiltrating cribriform carcinomas. The hormone receptor status, proliferation labeling index, and HER/2 immunoreactivity had been previously investigated in all the cases. Three (15%) adenoid cystic carcinomas and all infiltrating tubular and cribriform carcinomas showed estrogen receptor and/or progesterone receptor immunoreactivity (P<0.00001 for estrogen and P=0.00002 for progesterone receptors). Adenoid cystic carcinomas consistently lacked any immunoreactivity for HER/2, whereas three (15%) infiltrating and cribriform carcinomas showed weak and incomplete membrane staining (P=0.23077). Membranous immunoreactivity for c-kit was found in all except one (predominantly basaloid) adenoid cystic carcinomas (95%), and in none of the infiltrating tubular and cribriform carcinomas (P<0.00001). Nuclear immunoreactivity for p63 was found in all except three (predominantly basaloid) adenoid cystic carcinomas (85%) and in none of the infiltrating tubular and cribriform carcinomas (P<0.00001). All infiltrating tubular and cribriform carcinomas and 18/20 (90%) adenoid cystic carcinomas showed immunoreactivity for e-cadherin (P=0.48718). In summary, adenoid cystic carcinomas showed the following phenotype: estrogen receptor(-)/progesterone receptor(-)/c-kit(+)/p63(+) (13 cases, 65%), estrogen receptor(-)/progesterone receptor/c-kit(+)/p63(-) (three cases, 15%), estrogen receptor(-)/progesterone receptor(-)/c-kit(-)/p63(+) (one case, 5%), estrogen receptor(+)/progesterone receptor(+)/c-kit(+)/p63(+) (two cases, 10%), and estrogen receptor(+)/progesterone receptor(-)/c-kit(+)/p63(+) (one case). By contrast, all the infiltrating tubular and cribriform carcinomas showed the estrogen receptor(+)/progesterone receptor(+)/c-kit(-)/p63(-) phenotype. Our data provide evidence that immunoreactivity for c-kit and/or p63 may be useful in differentiating adenoid cystic carcinomas from other types of breast cancer.Modern Pathology advance online publication, 22 April 2005; doi:10.1038/modpathol.3800423.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15846389&dopt=Abstract progesterone, progesterone cream



progesterone cream
Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro.

Coughlan T, Gibson C, Murphy S.

Institute of Cell Signalling, Queen's Medical Centre, University of Nottingham, UK.

Nitric oxide (NO) is produced in the CNS following injury-induced expression of inducible nitric oxide synthase (iNOS), yet its role as protective or damaging is unclear. Previous studies investigating the therapeutic potential of female sex steroids in stroke and trauma suggest that NO from this source is harmful, since oestradiol and progesterone decreased the level of iNOS expression in vitro and improved neurological outcome. We investigated the effects of progesterone on stroke-induced expression of iNOS in mice, as well as cytokine-induced expression of iNOS and its transcriptional activators in cells relevant to injury. We observed a significant reduction in stroke-induced iNOS transcript in progesterone-treated mice and in cultured macrophages. In contrast, progesterone significantly amplifed cytokine-induced iNOS mRNA in cultured primary astrocytes, although the expression of protein was decreased. We sequenced upstream of the 1.5 kb reported iNOS promoter region and identified a potential progesterone response element (PRE). Astrocytes transiently transfected with iNOS promoter/CAT reporter gene constructs containing the PRE displayed a significant increase in induction of CAT expression after progesterone treatment, and this was diminished in cells transfected with a construct containing a disrupted PRE. These observations suggest the involvement of iNOS in the neuroprotective effects of progesterone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15857396&dopt=Abstract progesterone, progesterone cream