progesterone cream
Nitric oxide induces extensive apoptosis in endometrial epithelial cells in the presence of progesterone: involvement of mitogen-activated protein kinase pathways.

Li HY, Chang SP, Yuan CC, Chao HT, Ng HT, Sung YJ.

Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.

During trophoblast invasion, luminal and glandular endometrial epithelial cells (EEC) have been found to undergo apoptosis through undetermined mechanisms. We postulate that nitric oxide (NO) and progesterone may mediate apoptosis in EEC because they are produced by trophoblasts at concentrations that can cause apoptosis in non-uterine cells. Using a cultured EEC line, RL95-2, we found that sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP), two commonly used NO-releasing agents, caused the death of EEC in a dose-dependent manner and progesterone markedly enhanced NO-induced cytotoxicity. Cells treated with NO/progesterone showed a significant increase in the percentage of condensed nuclei, as detected by DAPI staining, and in caspase-3 activity, indicating that these cells underwent apoptosis. Immunoblot analysis revealed that SNP/NO could activate extracellular signal-regulated kinase (ERK) and, to a lesser extent, p38 mitogen-activated protein kinase (MAPK). While pretreatment with PD98059 (an ERK inhibitor) did not prevent cell death, the addition of SB203580 (a p38 MAPK inhibitor) effectively rescued the cells from NO/progesterone treatment. Moreover, SNP/NO-induced p38 MAPK activation was significantly up-regulated by progesterone. Our results demonstrate that NO and progesterone may synergistically activate p38 MAPK to induce apoptosis in EEC, a process that may facilitate implantation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11470863&dopt=Abstract progesterone, progesterone cream



progesterone cream
Production and localisation of angiotensin II in the bovine early corpus luteum: a possible interaction with luteal angiogenic factors and prostaglandin F2 alpha.

Kobayashi S, Berisha B, Amselgruber WM, Schams D, Miyamoto A.

Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.

The newly formed corpus luteum (CL) rapidly develops after ovulation and has the features of active vascularisation and mitosis of steroidogenic cells. These stage-specific mechanisms also may contribute to gain the function of prostaglandin F2 alpha (PGF2 alpha)-resistant CL at this stage. Recent studies suggest that the vasoactive peptide angiotensin II (Ang II) regulates luteal function. Thus, this study aimed to investigate (i) the expression of angiotensin-converting enzyme (ACE) mRNA by RT-PCR and the ACE protein expression by immunohistochemistry, (ii) the effects of angiogenic growth factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), on the secretion of Ang II, PGF2 alpha, progesterone and oxytocin (OT), and (iii) the effects of luteal vasoactive peptides (Ang II and endothelin-1 (ET-1)) or OT on the secretion of PGF2 alpha, progesterone and OT from bovine early CL (days 3--4 of the oestrous cycle), and evaluate a possible interaction of these substances with PGF2 alpha. The expression of mRNA for ACE was found in theca interna of mature follicle, early CL and endothelial cells from developing CL as well as pituitary and kidney, but granulosa cells of mature follicle were negative. The immunohistochemical analysis revealed that blood capillaries (endothelial cells) were stained for ACE, but luteal cells were negative in early CL. To examine the effects of substances on the secretory function of the CL, an in vitro microdialysis system was used as a model. The infusion of bFGF and VEGF stimulated Ang II and PGF2 alpha secretion as well as progesterone, but not OT secretion in early CL. The infusion of Ang II after PGF2 alpha infusion continued the stimulatory effect on progesterone and OT release within early CL until 3 h thereafter. However, the infusion of ET-1 alone had no effect on progesterone or OT release. The infusion of luteal peptides such as Ang II and OT stimulated PGF2 alpha secretion, whereas the infusion of ET-1 did not. In conclusion, the overall results of this study indicate that a functional angiotensin system exists on the endothelial cells of early CL, and that angiogenic factors bFGF and VEGF upregulate luteal Ang II and PGF2 alpha secretion, which fundamentally supports the mechanism of progesterone secretion in bovine early CL. This idea supports the concept that the local regulatory mechanism involved in active angiogenesis ensures the progesterone secretion in the developing CL in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11479133&dopt=Abstract progesterone, progesterone cream



progesterone cream
The classical progesterone receptor associates with p42 MAPK and is involved in phosphatidylinositol 3-kinase signaling in Xenopus oocytes.

Bagowski CP, Myers JW, Ferrell JE Jr.

Division of Chemical Biology, Stanford University, Stanford, California 94305-5174, USA.

The induction of Xenopus laevis oocyte maturation by progesterone is a striking example of a steroid hormone-mediated event that does not require transcription. Here we have investigated the role of the classical progesterone receptor in this nongenomic signaling. The Xenopus progesterone receptor (XPR) was predominantly cytoplasmic; however, a significant fraction ( approximately 5%) of one form of the receptor (p82 XPR) was associated with the plasma membrane-containing P-10,000 fraction, compatible with the observation that membrane-impermeant derivatives of progesterone can induce maturation. XPR co-precipitated with active phosphatidylinositol 3-kinase. The phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin delayed progesterone-induced maturation and completely blocked the insulin-dependent maturation, indicating that the association of XPR with PI3-K could be functionally important. We also examined whether the nongenomic signaling properties of XPR can account for the ability of glucocorticoids and the progesterone antagonist RU486 to induce maturation. We found that none of these steroids cause XPR to become associated with active PI3-K; thus, association of XPR with active PI3-K is progesterone-specific. Finally, we showed that p42 mitogen-activated protein kinase (MAPK) associates with XPR after progesterone-induced germinal vesicle breakdown and that active recombinant MAPK is able to phosphorylate p110 XPR in vitro. These findings demonstrate that the classical progesterone receptor is involved in progesterone-induced nongenomic signaling in Xenopus oocytes and provide evidence that p42 MAPK and PI3-K activity are directly associated with the classical progesterone receptor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11479298&dopt=Abstract progesterone, progesterone cream



progesterone cream
Diabetes and depot medroxyprogesterone contraception in Navajo women.

Kim C, Seidel KW, Begier EA, Kwok YS.

Robert Wood Johnson Clinical Scholars Program, Box 357183, University of Washington, Seattle, WA 98195-7183, USA. cathykim u.washington.edu

BACKGROUND: Depot medroxyprogesterone acetate contraception is widely used in Navajo women, a high-risk population for diabetes mellitus. However, depot medroxyprogesterone may lead to weight gain and independently decrease insulin sensitivity. We studied the association between depot medroxyprogesterone and development of diabetes in Navajo women. METHODS: We studied Navajo women aged 18 to 50 years who had seen a health care provider at a Navajo Area Indian Health Service clinic at least once in 1998. Diabetic cases (n = 284) and nondiabetic controls (n = 570) were matched by age. Medical records were reviewed to determine contraception use before the diagnosis date of diabetes. RESULTS: Users of depot medroxyprogesterone were more likely to develop diabetes than patients who had used combination estrogen-progestin oral contraception only (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.8-7.9). The excess risk persisted after adjustment for body mass index (OR, 3.6; 95% CI, 1.6-7.9). Longer use was associated with greater risk of diabetes. Users of depot medroxyprogesterone were also more likely to develop diabetes than patients who had never used hormonal contraception, although excess risk was smaller (OR, 2.4; 95% CI, 1.4-3.6). CONCLUSIONS: Depot medroxyprogesterone contraception was associated with a greater risk of diabetes compared with combination oral contraceptive use only. Risk was associated with length of use and persisted after adjustment for body mass index. Additional research is needed for confirmation, but this risk should be considered in contraceptive choice for women at high risk for diabetes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11485510&dopt=Abstract progesterone, progesterone cream



progesterone cream
Effects of progesterone synthesized de novo in the developing Purkinje cell on its dendritic growth and synaptogenesis.

Sakamoto H, Ukena K, Tsutsui K.

Laboratory of Brain Science, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.

De novo steroidogenesis from cholesterol is a conserved property of vertebrate brains, and such steroids synthesized de novo in the brain are called neurosteroids. The identification of neurosteroidogenic cells is essential to the understanding of the physiological role of neurosteroids in the brain. We have demonstrated recently that neuronal neurosteroidogenesis occurs in the brain and indicated that the Purkinje cell actively synthesizes several neurosteroids de novo from cholesterol in vertebrates. Interestingly, in the rat, this neuron actively synthesizes progesterone de novo from cholesterol only during neonatal life, when cerebellar cortical formation occurs most markedly. Therefore, in this study, the possible organizing actions of progesterone during cerebellar development have been examined. In vitro studies using cerebellar slice cultures from newborn rats showed that progesterone promotes dose-dependent dendritic outgrowth of Purkinje cells but dose not affect their somata. This effect was blocked by the anti-progestin RU 486 [mifepristone; 17beta-hydroxy-11beta-(4-methylaminophenyl)-17alpha-(1-propynyl) estra-4,9-dien-3 one-6-7]. In vivo administration of progesterone to pups further revealed an increase in the density of Purkinje spine synapses electron microscopically. In contrast to progesterone, there was no significant effect of 3alpha,5alpha-tetrahydroprogesterone, a progesterone metabolite, on Purkinje cell development. Reverse transcription-PCR-Southern and immunocytochemical analyses showed that intranuclear progesterone receptors were expressed in Purkinje cells. These results suggest that progesterone promotes both dendritic outgrowth and synaptogenesis in Purkinje cells through intranuclear receptor-mediated mechanisms during cerebellar development. Such organizing actions may contribute to the formation of the cerebellar neuronal circuit.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11487645&dopt=Abstract progesterone, progesterone cream



progesterone cream
Phenanthrenequinone disrupts progesterone production in rat luteal cells.

Nykamp JA, Bols NC, Carlson JC.

Biology Department, University of Waterloo, N2L 3G1, Waterloo, Ontario, Canada.

The ability of the environmental contaminant phenanthrene (PH) and its photooxidized product phenanthrenequinone (PHQ) to disrupt progesterone secretion was examined in a model system of in vitro suspensions of luteal cells from the rat. Treatment with PHQ dramatically inhibited luteinizing hormone (LH) stimulated progesterone secretion. PHQ also generated a significant increase in reactive oxygen species (ROS). In the absence of LH, however, PHQ stimulated a small increase in basal progesterone secretion. The parent compound, PH, did not alter progesterone or ROS release. Since there is evidence that PHQ lowers the activity of nitric oxide synthase (NOS) and that nitric oxide (NO) affects progesterone production, we examined the response to the NOS inhibitors N-monomethyl-L-arginine, Zn protoporphyrin-9, and aminoguanidine in luteal cells. However, there was no effect of these agents on LH stimulated progesterone secretion. These results indicated that PHQ is a potent disrupter of progesterone secretion and should perhaps be considered in assessing the risk of PH to humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11489595&dopt=Abstract progesterone, progesterone cream



progesterone cream
Reconstituted normal human breast in nude mice: estrogen and progesterone receptors regulation.

Yang J, Guzman R, Nandi S.

Cancer Research Laboratory and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.

Actions of estrogen and progesterone on normal human breast are mediated by their respective receptors. Since receptor regulation studies in humans are difficult to perform, we have utilized our model system of reconstituted normal human breast in nude mice to determine expression of estrogen and progesterone receptors in response to exogenous estrogen and progesterone. In normal human breast in situ, only a subset of epithelial cells (about 10%) are positive for estrogen receptor. These cells which remain positive after transplantation into nude mice can be completely downregulated by administration of exogenous estrogen resulting in all transplanted human breast epithelial cells now being negative for estrogen receptor. Exogenous estrogen also upregulates the progesterone receptor in a subset of human breast epithelial cells rather than in all cells. Exogenous progesterone, alone or in combination with estrogen, did not affect the estrogen or progesterone receptors. Double immunofluorescent labelings for a proliferation marker and progesterone receptor in both surgical specimens and nude mice transplants demonstrate that proliferation and progesterone receptor expression do not take place in the same cell. Our in vivo model system enables studies on the biology of primary normal human breast epithelial cells which otherwise are difficult to perform in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11491019&dopt=Abstract progesterone, progesterone cream