Effects of progesterone, levonorgestrel and medroxyprogesterone acetate on apoptosis in human endometrial endothelial cells

Choksuchat, Chainarong; Zhao, Shumei; Deutch, T.D.; Kimble, Thomas; Archer, David F.

doi:10.1016/j.contraception.2008.08.008

Cited by 10 publications

(8 citation statements)

References 37 publications

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“…However, the same strategy of progesterone supplementation, when used in endometrial explants, does not affect apoptosis, despite effectively maintaining the histological integrity of explanted tissue (Li et al, 2005). In isolated endometrial cells in culture, progesterone actually induces apoptosis (Li et al, 2001;Choksuchat et al, 2009;Tang et al, 2009), an effect that may be consistent with reports of antiapoptotic actions of mifepristone in endometrial biopsies from progestogen users (Jain et al, 2006). Furthermore, progesterone physiologically down-regulates endometrial Bcl-2 expression, which decreases at the early secretory phase (von Rango et al, 1998) and increases upon mifepristone administration (Critchley et al, 1999;Fig.…”

Section: Sex Steroid Hormones and Apoptosismentioning

confidence: 99%

Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis

Reis

Petraglia

Taylor

2013

Human Reproduction Update

220

172

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Estrogens and progestogens modulate chemotaxis and apoptosis in human endometrium and endometriotic cells and tissues. These endocrine and paracrine pathways are perturbed in women with endometriosis, contributing to inflammatory responses, abnormal tissue remodeling, therapeutic refractoriness and disease persistence. Ultimately, they promote adhesion formation and the clinical symptoms of pelvic pain and infertility. A more detailed understanding of the molecular mechanisms involved will offer new opportunities for novel pharmacological strategies to diagnose and treat endometriosis.

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Section: Sex Steroid Hormones and Apoptosismentioning

confidence: 99%

Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis

Reis

Petraglia

Taylor

2013

Human Reproduction Update

220

172

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“…Progesterone is well documented to be protective in many different experimental models of disease and neurodegeneration (Gonzalez Deniselle et al ., ,b; Gonzalez et al ., ; Compagnone, ; Espinosa‐García et al ., ; Yousuf et al ., ; Qin et al ., ). Affecting several different cellular processes, it can effectively inhibit apoptosis and inflammation (Roglio et al ., ; Choksuchat et al ., ; Yu et al ., ), fundamental in its potential as a treatment of RP. Despite this, the mechanism by which progesterone works in the CNS and specifically in the retina remains unclear.…”

Section: Introductionmentioning

confidence: 98%

The synthetic progesterone Norgestrel is neuroprotective in stressed photoreceptor‐like cells and retinal explants, mediating its effects via basic fibroblast growth factor, protein kinase A and glycogen synthase kinase 3β signalling

Jackson

Cotter

2016

Eur J of Neuroscience

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The synthetic progesterone Norgestrel has been shown to have proven neuroprotective efficacy in two distinct models of retinitis pigmentosa: the rd10/rd10 (B6.CXBI-Pde6b(rd10)/J) mouse model and the Balb/c light-damage model. However, the cellular mechanism underlying this neuroprotection is still largely unknown. Therefore, this study aimed to examine the downstream signalling pathways associated with Norgestrel both in vitro and ex vivo. In this work, we identify the potential of Norgestrel to rescue stressed 661W photoreceptor-like cells and ex vivo retinal explants from cell death over 24 h. Norgestel is thought to work through an upregulation of neuroprotective basic fibroblast growth factor (bFGF). Analysis of 661W cells in vitro by real-time polymerase chain reaction (rt-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting revealed an upregulation of bFGF in response to Norgestrel over 6 h. Specific siRNA knockdown of bFGF abrogated the protective properties of Norgestrel on damaged photoreceptors, thus highlighting the crucial importance of bFGF in Norgestrel-mediated protection. Furthermore, Norgestrel initiated a bFGF-dependent inactivation of glycogen synthase kinase 3β (GSK3β) through phosphorylation at serine 9. The effects of Norgestrel on GSK3β were dependent on protein kinase A (PKA) pathway activation. Specific inhibition of both the PKA and GSK3β pathways prevented Norgestrel-mediated neuroprotection of stressed photoreceptor cells in vitro. Involvement of the PKA pathway following Norgestrel treatment was also confirmed ex vivo. Therefore, these results indicate that the protective efficacy of Norgestrel is, at least in part, due to the bFGF-mediated activation of the PKA pathway, with subsequent inactivation of GSK3β.

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“…Similarly to many other drugs, MPA elicits side effects: several studies have found it associated with a variable increase in insulin levels, particularly in diabetic or obese women; it reduces high-density lipoproteins and changes the elasticity of the arterial endothelium; and, through its hypoestrogenic affect it causes imbalance between bone resorption and formation which results in bone-mineral density decline (for review see [17]). A recent study demonstrated that use of MPA results in impairment of endometrial capillary integrity, because of its apoptotic effect on endometrial endothelial cells [18]; MPA also has been known for many years as an inducer of mammary cancer (for review see [19]). The adverse health effects of MPA, the obvious effect it has on women's fertility, and the prohibitions that have been issued by the European Commission, China, and other countries on its use as an anabolic steroid in veterinary medicine, all indicate the need to maintain accurate identification and monitoring of small amounts of MPA in environmental, water, and food samples, in order to prevent exposure of "non-target" populations to the drug.…”

Section: Introductionmentioning

confidence: 99%

Development of Immunochemical Methods for Purification and Detection of the Steroid Drug Medroxyprogesterone Acetate

Bronshtein¹,

Krol²,

Schlesinger³

et al. 2012

JEP

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An immunochemical sol-gel-based immunoaffinity purification (IAP) method for purification and detection of the progestin drug medroxyprogesterone acetate (MPA) was developed. A polyclonal antibody (Ab) for MPA was generated, and two competitive (indirect and direct) sensitive enzyme-linked immunosorbent assays (ELISAs) for its detection were developed and implemented to determine the recovery and efficiency of the sol-gel based IAP method. The detection limits of the assays were 1.4 ± 0.2 ng·mL^-1 (n = 4) and 4.0 ± 0.4 ng·mL^-1 (n = 25) for the indirect and direct ELISAs, respectively. The Abs did not exhibit cross-reactivity with any other progestin or steroid hormone, with the exception of megestrol acetate, with which the Ab exhibited 76% cross-reactivity. The sol-gel IAP method successfully eliminated serum interference to a degree that enabled ELISA analysis of spiked serum samples. This method was also found fully compatible with subsequent chemical analytical methods, such as liquid chromatography followed by mass spectrometry (LC-MS/MS). The approaches developed in this study form a basis for analysis of MPA in biological samples and may be further used to study population exposure to MPA and to monitor MPA contamination in water samples

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Effects of progesterone, levonorgestrel and medroxyprogesterone acetate on apoptosis in human endometrial endothelial cells

Cited by 10 publications

References 37 publications

Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis

Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis

The synthetic progesterone Norgestrel is neuroprotective in stressed photoreceptor‐like cells and retinal explants, mediating its effects via basic fibroblast growth factor, protein kinase A and glycogen synthase kinase 3β signalling

Development of Immunochemical Methods for Purification and Detection of the Steroid Drug Medroxyprogesterone Acetate

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