Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells

Piccinato, Carla de Azevedo; Neme, R.M.; Torres, Natália; Sanches, Lívia Rentas; Derogis, Priscilla Bento Mattos Cruz; Brudniewski, H.F.; Silva, Júlio C. Rosa e; Ferriani, Rui Alberto

doi:10.1016/j.jsbmb.2015.12.025

Cited by 32 publications

(37 citation statements)

References 31 publications

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“…These are novel data that have not been described before, particularly because so far steroidogenesis and steroid metabolism have been mostly attributed to the epithelial compartment. Yet, data from previous study in our laboratory (Piccinato et al 2016) and the present work highlight the need of future studies regarding the impact of stromal cells on estradiol concentration in the endometrium and endometriotic lesions, as the role of different cellular compartments in the metabolism of estradiol has not been exploited.…”

Section: Discussionmentioning

confidence: 77%

“…The 17β-estradiol levels in the medium were determined using the LC-MS/MS method, as described for estradiol determination previously (Piccinato et al 2016). After protein precipitation, medium samples containing a deuterated internal standard (17-hydroxyprogesterone-d8, CDN Isotopes Inc., Pointe Claire, QC, Canada) were filtered and injected onto a Kinetex C18 HPLC column (Phenomenex, Torrance, CA, USA), using an Agilent 1260 LC system (Agilent Technologies).…”

Section: Measurements Of Estradiol In Cell Culture Medium By Liquid Cmentioning

confidence: 99%

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Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

Piccinato¹,

Neme²,

Torres³

et al. 2016

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Endometriosis is an estrogen-dependent disease affecting up to 10% of all premenopausal women. There is evidence that different endometriosis sites show distinct local estrogen concentration, which, in turn, might be due to a unique local estrogen metabolism. We aimed to investigate whether there was a site-specific regulation of selected enzymes responsible for the oxidative metabolism of estrogens in biopsy samples and endometrial and endometriotic stromal cells. Cytochrome P450 (CYP) 1A1 and CYP1B1 mRNA and protein expressions in deep-infiltrating (rectal, retossigmoidal, and uterossacral) lesions, superficial (ovarian and peritoneal) lesions, and eutopic and healthy (control) endometrium were evaluated by real-time PCR and western blot. Using a cross-sectional study design with 58 premenopausal women who were not under hormonal treatment, we were able to identify an overall increased CYP1A1 and CYP1B1 mRNA expression in superficial lesions compared with the healthy endometrium. CYP1A1 mRNA expression in superficial lesions was also greater than in the eutopic endometrium. Interestingly, we found a similar pattern of CYP1A1 and CYP1B1 expression in in vitro stromal cells isolated from ovarian lesions (n = 3) when compared with stromal cells isolated from either rectum lesions or eutopic endometrium. In contradiction, there was an increased half-life of estradiol (measured by HPLC-MS-MS) in ovarian endometriotic stromal cells compared with paired eutopic stromal endometrial cells. Our results indicate that there is a site-dependent regulation of CYP1A1 and CYP1B1 in ovarian/peritoneal lesions and ovarian endometriotic stromal cells, whereas a slower metabolism is taking place in these cells.

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Section: Discussionmentioning

confidence: 77%

Section: Measurements Of Estradiol In Cell Culture Medium By Liquid Cmentioning

confidence: 99%

Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

Piccinato¹,

Neme²,

Torres³

et al. 2016

Reproduction

Self Cite

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show abstract

“…Overall, most studies agree that there is a differential STS mRNA expression between eutopic and ectopic endometrium, in spite of conflicting results in regards of STS expression among endometriotic lesions. Data from our group show higher STS mRNA expression in deep-infiltrating and superficial lesions when compared to eutopic and normal endometrium, with neither differences between ectopic lesions, nor between eutopic and normal endometrium (Piccinato et al 2016a). Some authors have reported higher STS mRNA expression in ovarian lesions when compared to endometrium from patients with myoma (Smuc et al 2007(Smuc et al , Šmuc et al 2009, while others have not been able to detect differences between lesions, compared to the eutopic endometrium (Colette et al 2013, Huhtinen et al 2014.…”

Section: Steroid Sulphatasementioning

confidence: 50%

SULFATION PATHWAYS: Contribution of intracrine oestrogens to the aetiology of endometriosis

Piccinato

Malvezzi

Gibson

et al. 2018

Journal of Molecular Endocrinology

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Endometriosis is an incurable hormone-dependent inflammatory disease that causes chronic pelvic pain and infertility characterized by implantation and growth of endometrial tissue outside the uterine cavity. Symptoms have a major impact on the quality of life of patients resulting in socioeconomic, physical and psychological burdens. Although the immune system and environmental factors may play a role in the aetiology of endometriosis, oestrogen dependency is still considered a hallmark of the disorder. The impact of oestrogens such as oestrone and particularly, oestradiol, on the endometrium or endometriotic lesions may be mediated by steroids originating from ovarian steroidogenesis or local intra-tissue production (intracrinology) dependent upon the expression and activity of enzymes that regulate oestrogen biosynthesis and metabolism. Two key pathways have been implicated: while there is contradictory data on the participation of the aromatase enzyme (encoded by ), there is increasing evidence that the steroid sulphatase pathway plays a role in both the aetiology and pathology of endometriosis. In this review, we consider the evidence related to the pathways leading to oestrogen accumulation in endometriotic lesions and how this might inform the development of new therapeutic strategies to treat endometriosis without causing the undesirable side effects of current regimes that suppress ovarian hormone production.

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“…As early as in 1962, steroid disulfates (also referred to as bis-sulfates) were described as a constituent of human urine (Pasqualini & Jayle 1962). Falany and coworkers established for 24-hydroxycholesterol-3,24-disulfate that double sulfation leads to a terminal product that is resistant to reactivation by STS (Cook et al 2009).…”

Section: Steroid Disulfatesmentioning

confidence: 99%

“…Along with new evidence suggesting the importance of STS and SULT1E1 expression in endometriosis (Piccinato et al 2016), there are new insights into how desulfation impacts endometrial (Sinreih et al 2017) and ovarian (Ren et al 2015, Mungenast et al 2017 cancers. This work represents a growing interest in local estrogen metabolism and action in gynecological conditions (Rizner 2016.…”

Section: Gynecological Cancersmentioning

confidence: 99%

SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways

Foster

Mueller

2018

Journal of Molecular Endocrinology

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Sulfation and desulfation pathways represent highly dynamic ways of shuttling, repressing and re-activating steroid hormones, thus controlling their immense biological potency at the very heart of endocrinology. This theme currently experiences growing research interest from various sides, including, but not limited to, novel insights about phospho-adenosine-5'-phosphosulfate synthase and sulfotransferase function and regulation, novel analytics for steroid conjugate detection and quantification. Within this review, we will also define how sulfation pathways are ripe for drug development strategies, which have translational potential to treat a number of conditions, including chronic inflammatory diseases and steroid-dependent cancers.

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Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells

Cited by 32 publications

References 31 publications

Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

SULFATION PATHWAYS: Contribution of intracrine oestrogens to the aetiology of endometriosis

SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways

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