Effects of dydrogesterone and of its stable metabolite, 20-α-dihydrodydrogesterone, on nitric oxide synthesis in human endothelial cells  Tommaso Simoncini,

Slides:



Advertisements
Similar presentations
Raloxifene⁎ increases proliferation of human endothelial cells in association with increased gene expression of cyclins A and B1  Pilar J. Oviedo, B.Sc.,
Advertisements

Reduction of estrogen production by interleukin-6 in a human granulosa tumor cell line may have implications for endometriosis-associated infertility 
Volume 68, Issue 4, Pages (October 2005)
Iron overload–modulated nuclear factor kappa-B activation in human endometrial stromal cells as a mechanism postulated in endometriosis pathogenesis 
Shear stress-stimulated endothelial cells induce smooth muscle cell chemotaxis via platelet-derived growth factor-BB and interleukin-1α  Alan Dardik,
Cryoprotectants up-regulate expression of mouse oocyte AQP7, which facilitates water diffusion during cryopreservation  Ya-Jing Tan, M.Sci., Yun Xiong,
Adiponectin increases insulin-like growth factor I-induced progesterone and estradiol secretion in human granulosa cells  Christine Chabrolle, M.D., Lucie.
2-Methoxyestradiol causes functional repression of transforming growth factor β3 signaling by ameliorating Smad and non-Smad signaling pathways in immortalized.
Sphingosine-1-phosphate inhibits H2O2-induced granulosa cell apoptosis via the PI3K/Akt signaling pathway  Tatsuo Nakahara, M.D., Akira Iwase, M.D., Ph.D.,
Resistin decreases insulin-like growth factor I–induced steroid production and insulin- like growth factor I receptor signaling in human granulosa cells 
Fernando Zegers-Hochschild, M.D.  Fertility and Sterility 
Interleukin-25 induced by human chorionic gonadotropin promotes the proliferation of decidual stromal cells by activation of JNK and AKT signal pathways 
Arachidonic acid regulation of the cytosolic phospholipase A2α/cyclooxygenase-2 pathway in mouse endometrial stromal cells  Zhen-Ao Zhao, Ph.D., Zhi-Rong.
Michael M. Alper, M.D.  Fertility and Sterility 
Curcumin, a nutritional supplement with antineoplastic activity, enhances leiomyoma cell apoptosis and decreases fibronectin expression  Minnie Malik,
The selective progesterone receptor modulator CDB4124 inhibits proliferation and induces apoptosis in uterine leiomyoma cells  Xia Luo, Ph.D., Ping Yin,
Chakradhari Sharan, Ph. D. , Sunil K. Halder, Ph. D
Volume 63, Issue 2, Pages (February 2003)
Marina Ines Flamini, Ph. D. , Angel Matias Sanchez, Ph. D
Ovarian stimulation modulates steroid receptor expression and spheroid attachment in peri-implantation endometria: studies on natural and stimulated cycles 
Hypoxia inducible factor and microvessels in peri-implantation endometrium of women with recurrent miscarriage  Xiaoyan Chen, M.Phil., Lingming Jiang,
Hadas Bar-Joseph, Ph. D. , Ido Ben-Ami, M. D. , Ph. D
Translocation of protein kinase C isoforms is involved in propofol-induced endothelial nitric oxide synthase activation  L. Wang, B. Wu, Y. Sun, T. Xu,
Dienogest inhibits nerve growth factor expression induced by tumor necrosis factor-α or interleukin-1β  Shizuka Mita, M.S., Yutaka Shimizu, Ph.D., Ayumi.
The growth hormone–releasing hormone (GHRH) antagonist JV-1-36 inhibits proliferation and survival of human ectopic endometriotic stromal cells (ESCs)
In vitro effects of phthalate esters in human myometrial and leiomyoma cells and increased urinary level of phthalate metabolite in women with uterine.
Different effects of epidermal growth factor on smooth muscle cells derived from human myometrium and from leiomyoma  Yuanyuan Ren, M.Sc., Hao Yin, Ph.D.,
Ambient pressure upregulates nitric oxide synthase in a phosphorylated-extracellular regulated kinase– and protein kinase C–dependent manner  Angela G.
Transforming growth factor (TGF)-β1-induced human endometrial stromal cell decidualization through extracellular signal-regulated kinase and Smad activation.
Volume 56, Issue 4, Pages (October 1999)
Akio Horiguchi, Mototsugu Oya, Ken Marumo, Masaru Murai 
Association of a single dose of gonadotropin-releasing hormone antagonist with nitric oxide and embryo quality in in vitro fertilization cycles  Tsung-Hsien.
Oocyte cryopreservation
Growth hormone, insulin-like growth factor I, and leptin interaction in human cultured lutein granulosa cells steroidogenesis  Maria Karamouti, M.D, Panagoula.
Leukemia inhibitory factor increases the invasiveness of trophoblastic cells through integrated increase in the expression of adhesion molecules and pappalysin.
Volume 68, Issue 4, Pages (October 2005)
Sphingosine-1-phosphate–induced smooth muscle cell migration involves the mammalian target of rapamycin  William J. Tanski, MD, Suzanne M. Nicholl, PhD,
Estrogen receptor β agonist diarylpropionitrile inhibits lipopolysaccharide-induced regulated on activation normal T cell expressed and secreted (RANTES)
Gabriele Di Luozzo, MD, Jaya Bhargava, PhD, Richard J. Powell, MD 
Heparin inhibits interferon-γ signaling in human endometrial stromal cells by interference with the cellular binding of interferon-γ  Herbert Fluhr, M.D.,
Estrogens and androgens affect human luteal cell function
Volume 62, Issue 2, Pages (August 2002)
Role of glucocorticoid receptor in the inhibitory effect of medroxyprogesterone acetate on the estrogen-induced endothelial nitric oxide synthase phosphorylation.
Endocannabinoid system regulates migration of endometrial stromal cells via cannabinoid receptor 1 through the activation of PI3K and ERK1/2 pathways 
Chi-Hyun Park, Youngji Moon, Chung Min Shin, Jin Ho Chung 
Volume 65, Issue 5, Pages (May 2004)
Testosterone dependent androgen receptor stabilization and activation of cell proliferation in primary human myometrial microvascular endothelial cells 
Mevastatin inhibits proliferation of rat ovarian theca–interstitial cells by blocking the mitogen-activated protein kinase pathway  Jakub Kwintkiewicz,
Requirement of heart and neural crest derivatives–expressed transcript 2 during decidualization of human endometrial stromal cells in vitro  Hisayuu Shindoh,
Clomiphene citrate at 50: the dawning of assisted reproduction
Volume 127, Issue 4, Pages (October 2004)
Introduction Fertility and Sterility
Nitric oxide metabolite production in the human preimplantation embryo and successful blastocyst formation  Christopher W. Lipari, M.D., Jairo E. Garcia,
Volume 70, Issue 5, Pages (September 2006)
Prasun K. Datta, Elias A. Lianos  Kidney International 
Matthew A. Will, M. D. , Murugesan Palaniappan, Ph. D
Androgen signaling in decidualizing human endometrial stromal cells enhances resistance to oxidative stress  Takeshi Kajihara, M.D., Ph.D., Hideno Tochigi,
Histone deacetylase inhibitors down-regulate G-protein-coupled estrogen receptor and the GPER-antagonist G-15 inhibits proliferation in endometriotic.
Effects of mifepristone on expression of endothelial nitric oxide synthase in human endometrium during the implantation phase  Xiaoxi Sun, M.D., Xiaoyan.
Impairment of male reproductive function after sleep deprivation
Fertility and Sterility: an evaluation
Effect of ovarian steroids on gene expression profile in human uterine microvascular endothelial cells  Tadahiro Yasuo, M.D., Kotaro Kitaya, M.D.  Fertility.
The selective progesterone receptor modulator CDB4124 inhibits proliferation and induces apoptosis in uterine leiomyoma cells  Xia Luo, Ph.D., Ping Yin,
Lipopolysaccharide-promoted proliferation of endometriotic stromal cells via induction of tumor necrosis factor α and interleukin-8 expression  Yumiko.
Deon G. Uffort, Elizabeth A. Grimm, Julie A. Ellerhorst 
Differential effects of simvastatin on mesangial cells
In vitro sildenafil citrate use as a sperm motility stimulant
IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways  M. Zhang, Ph.D., Q. Zhou, M.D.,
Umber Agarwal, M. R. C. O. G. , Soha El Sheikh, F. R. C. Path. , Ph. D
Effects of visfatin on the cell proliferation and phosphorylation of ERK, Akt, and GSK-3β proteins in HCC cells. Effects of visfatin on the cell proliferation.
Presentation transcript:

Effects of dydrogesterone and of its stable metabolite, 20-α-dihydrodydrogesterone, on nitric oxide synthesis in human endothelial cells  Tommaso Simoncini, M.D., Ph.D., Antonella Caruso, M.D., Maria Silvia Giretti, M.D., Camila Scorticati, Ph.D., Xiao-Dong Fu, M.D., Silvia Garibaldi, M.D., Chiara Baldacci, M.D., Paolo Mannella, M.D., Letizia Fornari, M.D., Andrea R. Genazzani, M.D., Ph.D.  Fertility and Sterility  Volume 86, Issue 4, Pages 1235-1242 (October 2006) DOI: 10.1016/j.fertnstert.2006.05.018 Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Divergent transcriptional regulation of eNOS expression by DYD, DHD, P, and MPA in human endothelial cells. Steroid-deprived HUVECs were treated for 48 hours with 10 nmol/L P, 10 nmol/L MPA, 10 nmol/L DYD, or 10 nmol/L DHD in the presence or absence of the PR and GR antagonist RU486 (RU, 1 μmol/L). Alternatively, HUVECs were treated for 48 hours with 1 nmol/L E2 in the presence or absence of the previous compounds. (A and C): Nitrites released in the cell culture medium were assayed (yellow bars), and eNOS activity was tested in whole cell lysates (blue bars). (B and D): Endothelial nitric oxide synthase (eNOS) and von Willebrand (as loading control [vWF]) protein amounts were tested on whole cell protein extracts. (A): *P<.05 versus control (CON). (C): *P<.05 versus E2 alone. The experiments were repeated three times in quadruplicate (nitrites measurement) or in triplicate (eNOS activity) with comparable results, Western blot analyses were repeated three times, and representative blots are shown. Simoncini. Endothelial effects of dydrogesterone. Fertil Steril 2006. Fertility and Sterility 2006 86, 1235-1242DOI: (10.1016/j.fertnstert.2006.05.018) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 Concentration and time dependency of eNOS induction by DHD. Steroid-deprived HUVECs were treated for 48 hours (A–C) with increasing concentrations of DYD or DHD. Steroid-deprived HUVECs were treated for different times with 10 nmol/L DHD (D–E). (A and D): Nitrites released in the cell culture medium were assayed (yellow bars), and eNOS activity was tested in whole cell lysates (blue bars). (B, C, and E): Endothelial nitric oxide synthase (eNOS) and von Willebrand (as loading control [vWF]) protein amount were tested on whole cell protein extracts. *P<.05 versus control (CON). The experiments were repeated three times in quadruplicate (nitrites measurement) or in triplicate (eNOS activity) with comparable results, Western blot analyses were repeated three times, and representative blots are shown. Simoncini. Endothelial effects of dydrogesterone. Fertil Steril 2006. Fertility and Sterility 2006 86, 1235-1242DOI: (10.1016/j.fertnstert.2006.05.018) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Rapid eNOS activation by P and DHD (but not MPA) in endothelial cells. Steroid-deprived and serum-starved HUVECs were treated for 30 minutes with 10 nmol/L P, 10 nmol/L MPA, 10 nmol/L DYD, or 10 nmol/L DHD in the presence or absence of the PR and GR antagonist RU486 (RU, 1 μmol/L) (A–B). Steroid-deprived HUVECs were treated for 30 minutes with increasing concentrations of DHD (C). (A and C): Nitrites released in the cell culture medium were assayed (yellow bars) and eNOS activity was tested (blue bars) in whole cell lysates. (B): Endothelial nitric oxide synthase (eNOS) and von Willebrand (as loading control) (vWF) protein amounts were tested on whole cell protein extracts. *P<.05 versus control (CON). The experiments were repeated three times in quadruplicate (nitrites measurement) or in triplicate (eNOS activity) with comparable results, Western blot analyses were repeated three times, and representative blots are shown. Simoncini. Endothelial effects of dydrogesterone. Fertil Steril 2006. Fertility and Sterility 2006 86, 1235-1242DOI: (10.1016/j.fertnstert.2006.05.018) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 4 Differential recruitment of MAPK nongenomic signaling pathways by P, DYD, and DHD. Steroid-deprived and serum-starved HUVECs were treated for 30 minutes (A) or 5 minutes (B) with 10 nmol/L P, 10 nmol/L DYD, or 10 nmol/L DHD in the presence or absence of the MEK 1/2 inhibitor PD98059 (PD, 5 μmol/L) or of the PR and GR antagonist RU486 (RU, 1 μmol/L). Alternatively, HUVECs were treated for 30 minutes (A) or 5 minutes (B) with 1 nmol/L E2, in the presence or absence of the previous compounds. (A and C): Nitrites released in the cell culture medium were assayed (yellow bars) and eNOS activity was tested (blue bars) in whole cell lysates. (B and D): Wild-type or phosphorylated ERK 1/2 (P-ERK) was assayed. (A): *P<.05 versus control. (B): *P<.05 versus E2 alone. The experiments were repeated three times in quadruplicates (nitrites measurement) or in triplicates (eNOS activity) with comparable results, Western blot analyses were repeated three times, and representative blots are shown. Simoncini. Endothelial effects of dydrogesterone. Fertil Steril 2006. Fertility and Sterility 2006 86, 1235-1242DOI: (10.1016/j.fertnstert.2006.05.018) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions