Aromatase and Leiomyoma of the Uterus

Shozu, Makio; Murakami, Kouich; Inoue, Masakí

doi:10.1055/s-2004-823027

Cited by 84 publications

(18 citation statements)

References 39 publications

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“…However, such low expression of FSH receptor reflected high plasma concentration of free FSH, noted in the early stage of the menopausal period and not the negative feedback reaction. The reports available [52] stress the importance of high expression of aromatase in the uterine myoma cells, accompanied by residual expression in normal tissues of the myometrium.…”

Section: Discussionmentioning

confidence: 99%

Receptors of Hypothalamic-Pituitary-Ovarian-Axis Hormone in Uterine Myomas

Plewka

Marczyński

Morek

et al. 2014

BioMed Research International

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In this study the expression of GnRH, FSH, LH, ER-α, ER-β, and PR receptors was examined in uterine myomas of women in reproductive and perimenopausal age. In cases of GnRH and tropic hormones a membranous and cytoplasmic immunohistochemical reaction was detected, in cases of ER-α and PR the reaction was located in cell nucleus, and in the case of ER-β it manifested also a cytoplasmic location. In some of the examined cases the expression was detected in endometrium, myocytes, and endothelium of blood vessels, in uterine glands and myoma cells. In myometrium the level of GnRH and LH receptors increases with age, whereas the level of progesterone and both estrogen receptors decreases. In myomas of women in reproductive age, independently of their size, expression of GnRH, FSH, and LH receptors was more pronounced than in myometrium. In women of perimenopausal age, independently of myoma size, expression of LH and estrogen α receptors was higher while expression of GnRH receptors was lower than in myometrium. FSH receptor expression was not observed. Expression of estrogen receptor β was not affected by age of the woman or size of myoma. Analysis of obtained results indicates on existing in small myomas local feedback axis between GnRH-LH-progesterone.

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Section: Discussionmentioning

confidence: 99%

Receptors of Hypothalamic-Pituitary-Ovarian-Axis Hormone in Uterine Myomas

Plewka

Marczyński

Morek

et al. 2014

BioMed Research International

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“…Of relevance to this investigation, it is interesting to note that genes associated with steroid hormone regulation, the TGFB pathway and genes involved in the RA pathway make up a significant portion of genes that are differentially expressed in fibroid tissue compared with myometrium (refer to Table 1 for a brief summary; Sadan et al 1987, Dou et al 1996, Tsibris et al 2002, Skubitz & Skubitz 2003, Weston et al 2003, Shozu et al 2004, Arslan et al 2005, Leppert et al 2006, Zaitseva et al 2006, Roth et al 2007, Litovkin et al 2008, Lee et al 2010, Moore et al 2010, Davis et al 2013, Yin et al 2013.…”

Section: Introductionmentioning

confidence: 99%

Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium

Holdsworth-Carson¹,

Zaitseva²,

Girling³

et al. 2014

Reproduction

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Uterine fibroids are a prevalent gynaecological condition in reproductive-aged women and are the commonest reason for hysterectomy. The cellular composition of clonal fibroids are heterogeneous, with phenotypically dissimilar cells that include smooth muscle cells (SMC), vascular SMC (VSMC) and fibroblasts. The aim of our study was to investigate genes that are commonly differentially expressed between fibroid and myometrial whole tissues in phenotypically different sub-populations of cells isolated from fibroid and myometrium. Genes to be investigated by fluorescence-activated cell sorting, quantitative real-time PCR and immunocytochemistry include transforming growth factor b (TGFB) and retinoic acid (RA) signalling families and steroid hormone receptors. We hypothesised that each cell population isolated from fibroid and myometrium would differ in the expression of fibroid-associated genes. We demonstrated that phenotypically different cellular constituents of uterine fibroids differentially express cellular RA-binding protein 2 (CRABP2), progesterone receptor B (PRB) and TGFB receptor 2 mRNA in fibroid-derived cells of VSMC and SMC phenotype. CRABP2 mRNA was also differentially expressed in fibroblasts and VSMC sub-populations from within clonal fibroid tumours. We conclude that differential regulation of RA, TGFB and PR pathway transcription occurs in fibroid-associated SMC and -fibroblasts and that investigation of paracrine interactions between different cell types within the fibroid microenvironment provides an important new paradigm for understanding the pathophysiology of this common disease.

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“…In situ estrogen secretion in these tissues possibly plays physiological roles on breast development and bone closure. More importantly, over- and/or dysregulated expression of in situ aromatase plays a role in the pathogenesis of various diseases, such as breast cancer, endometrial cancer, endometriosis and uterine fibroid development [16–19].…”

Section: Aromatase: Gene Structure Expression and Enzymatic Activitiesmentioning

confidence: 99%

Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis

Shozu

Fukami

Ogata

2014

Expert Review of Endocrinology & Metabolism

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CYP19A1Aromatase excess syndrome is characterized by pre- or peripubertal onset of gynecomastia due to estrogen excess because of a gain-of-function mutation in the aromatase gene (CYP19A1). Subchromosomal recombination events including duplication, deletion, and inversion has been identified. The latter two recombinations recruit novel promoters for CYP19A1 through a unique mechanism. Gynecomastia continues for life, and although the general condition is well preserved, it may cause psychological issues. Minor symptoms (variably advanced bone age and short adult height), if present, are exclusively because of estrogen excess. Serum estradiol levels are elevated in 48% of affected males, but are not necessarily useful for diagnosis. Molecular analysis of CYP19A1 mutations is mandatory to confirm aromatase excess syndrome diagnosis. Furthermore, the use of an aromatase inhibitor can ameliorate gynecomastia.

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Aromatase and Leiomyoma of the Uterus

Cited by 84 publications

References 39 publications

Receptors of Hypothalamic-Pituitary-Ovarian-Axis Hormone in Uterine Myomas

Receptors of Hypothalamic-Pituitary-Ovarian-Axis Hormone in Uterine Myomas

Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium

Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis

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