Role of testosterone synthesized by skin melanocytes in preventing malignant transformation of nevi.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21066-e21066
Author(s):  
Elena Mikhaylovna Frantsiyants ◽  
Valeria Bandovkina ◽  
Yulia A. Pogorelova ◽  
Irina V. Kaplieva ◽  
Natalia D. Cheryarina ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Cutaneous Melanoma ◽  
Free Testosterone ◽  
Aromatase Activity ◽  
Genotoxic Effects ◽  
Dysplastic Nevi ◽  
Estrogen Synthesis ◽  
Steroid Binding ◽  
Pigmented Nevi

e21066 Background: Melanocytes are involved into the synthesis and metabolism of steroid hormones in the skin. Cutaneous melanoma in 75% of cases occurs in congenital or acquired pigmented nevi. There are no studies comparing local hormonogenesis in nevi and melanomas. The purpose of the study was a comparative analysis of hormone levels in tissues of dysplastic nevi and cutaneous melanoma (pТ1-2N0M0). Methods: Levels of prolactin (PRL), progesterone (P4), total and free testosterone (T and fT), estrone (E1) and estriol (E3) and sex steroid-binding globulin (SSBG) were studied by ELISA in 17 samples of рТ1-2N0M0 melanoma and in 23 samples of dysplastic nevi. Intact tissues (n = 15) obtained from non-cancer patients during surgical treatment was used as the control. Results: Levels of T in nevi, compared to intact tissues, were 1.4 times higher, fT – 8.7 times higher, while SSBG content was 1.9 times lower; E3 was 1.6 times higher, PRL – 1.4 times lower, and levels of E1 in nevi were similar to the values in intact tissues. рТ1-2N0M0 melanomas, compared to intact tissues, demonstrated local androgen imbalance: T levels were decreased by 1.8 times, while fT exceeded the norm by 1.8 times, and SSBG – by 6 times. E1 content increased by 1.6 times, E3 decreased by 2.8 times. The E1/E3 ratio in nevi was reduced by 1.6 times, while in melanoma it was increased by 4.4 times. The T/E1 ratio in nevi was increased by 1.4 times, and in melanoma it was decreased by 2.8 times. Levels of PRL and P4 in melanomas, nevi and in intact tissues did not differ significantly. Conclusions: Melanoma was characterized by hyperestrogenia due to increased levels of E1 and low E3 concentrations which caused malignant transformation of melanocytes. Most likely, in melanoma spent SVT estrone synthesis, as evidenced by increase in the E1 / E3 and decrease T / E1.Apparently, fT in melanoma is used for estrogen synthesis, as indicated by the E1/E3 increase and decrease in the T/E1 ratio. Increased E1 synthesis can contribute to the realization of estrogen genotoxic effects. These mechanisms are absent in tissues of nevi. Hyperandrogenism in nevi probably prevents malignant transformation due to low aromatase activity.

scholarly journals Aromatase expression in Xenopus oocytes: a three cell-type model for the ovarian estradiol synthesis

2011 ◽  
Vol 47 (2) ◽  
pp. 241-250 ◽  
Author(s):  
M Gohin ◽  
P Bodinier ◽  
A Fostier ◽  
J Bobe ◽  
F Chesnel
Keyword(s):  
Classical Model ◽  
Biological Significance ◽  
Type Model ◽  
Aromatase Activity ◽  
Steroid Synthesis ◽  
Aromatase Expression ◽  
Androgen Synthesis ◽  
Estrogen Synthesis ◽  
Estradiol Synthesis

In contrast to the classical model describing the synthesis of androgens and estrogens as restricted to somatic cells, a previous study demonstrated that Xenopus laevis oocytes participate in androgen synthesis. The objective of our study was to determine whether Xenopus oocytes are also involved in estrogen synthesis. More precisely, we analyzed aromatase expression by in situ hybridization and RT-QPCR and measured aromatase activity. Aromatase, the enzyme responsible for estrogen synthesis, appears to be expressed and active not only in the follicular cells but also in the vitellogenic oocytes. During late oogenesis, aromatase oocyte expression and activity decreased concomitantly with the trend observed in surrounding follicular layers. In order to investigate the role of estradiol-17β (E2), we studied its effect on oocyte meiotic resumption. It appears that, as in Rana pipiens, E2 inhibited the follicle-enclosed maturation of Xenopus oocytes, likely through inhibition of LH-induced maturation-inducing steroid synthesis. In addition, E2 exerted a slight enhancing action on denuded oocyte maturation whose biological significance remains unclear. Together, our results demonstrate that Xenopus oocyte significantly participates in ovarian E2 synthesis and this may be a common feature of vitellogenic vertebrates.

scholarly journals Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer

2021 ◽  
Vol 22 (1) ◽  
pp. 438
Author(s):  
Yunho Jin ◽  
Yoo Jin Choi ◽  
Kyu Heo ◽  
Seong Joon Park
Keyword(s):  
Breast Cancer ◽  
Developmental Stages ◽  
Therapeutic Option ◽  
Chemotherapeutic Agents ◽  
Common Type ◽  
Aromatase Activity ◽  
Estrogen Synthesis ◽  
Radiation Induced ◽  
Estrogen Biosynthesis

Breast cancer is the most common type of cancer. In the developmental stages of breast cancer, estrogens are strongly involved. As estrogen synthesis is regulated by the enzyme aromatase, targeting the activity of this enzyme represents a therapeutic option. The pineal hormone melatonin may exert a suppressive role on aromatase activity, leading to reduced estrogen biosynthesis. A melatonin-mediated decrease in the expression of aromatase promoters and associated genes would provide suitable evidence of this molecule’s efficacy as an aromatase inhibitor. Furthermore, melatonin intensifies radiation-induced anti-aromatase effects and counteracts the unwanted disadvantages of chemotherapeutic agents. In this manner, this review summarizes the inhibitory role of melatonin in aromatase action, suggesting its role as a possible oncostatic molecule in breast cancer.

A Two-Year Regional Program for the Early Detection of Cutaneous Melanoma

2003 ◽  
Vol 89 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Andrea Veronesi ◽  
Maria Antonietta Pizzichetta ◽  
Clelia De Giacomi ◽  
Alessandro Gatti ◽  
Giusto Trevisan ◽  
...  
Keyword(s):  
General Practitioner ◽  
Plastic Surgery ◽  
General Practitioners ◽  
Cutaneous Melanoma ◽  
Thickness Distribution ◽  
Skin Lesions ◽  
Dysplastic Nevi ◽  
Program Support ◽  
Friuli Venezia Giulia

Background A regional program for the early diagnosis of cutaneous melanoma involving general practitioners was effective in 1997–1998 in the Friuli Venezia Giulia region in Northern Italy. The aim of the 2-year program was to evaluate the role of a skin examination performed by general practitioners in people older than 18 years without known skin lesions and spontaneously presenting to their offices for any reason, with referral of suspect cases to a pre-identified regional dermatology or plastic surgery institution. Methods In the preparatory phase (late 1995 and 1996), all general practitioners operating in the Friuli Venezia Giulia region (n = 1,038) were asked to participate in the program. Support from all regional dermatology, pathology and plastic surgery institutions was obtained. Operational procedures for the management of referred people were defined, and educational meetings directed to general practitioners interested in the program were held. Skin examinations by general practitioners started at the end of 1996 and took place during 1997 and 1998. Subsequently, information was obtained from participating general practitioners and from pathology institutions about the number and thickness of diagnosed melanomas, as well as the number of diagnosed skin carcinomas and dysplastic nevi. In addition, the thickness distribution of all melanomas diagnosed in the Friuli Venezia Giulia region before and during the program was obtained. Results A total of 153 general practitioners participated in the program, but only 74 were active and assessable. A total of 11,040 skin examinations was performed by these 74 general practitioners (median, 75 per general practitioner). In all, 820 people (7.4%) were referred for dermatological evaluation (median, 8 per general practitioner). Among these 820 people, at least 38 melanomas (4.6% of referred cases) were detected (18 ≤1.5 mm, 11 >1.5 mm thick, unknown in 9). The dermatological examinations/diagnosed melanomas ratio was 21. In addition, 94 skin carcinomas and 50 dysplastic nevi were detected. At the regional level, the percentage of thin melanomas rose from 65.3% in 1995–96 to 72.2% in 1997–98 (P = 0.04), whereas the number of thick melanomas declined. Conclusions In our study, only a few general practitioners chose, in the absence of incentives, to participate in the study. However, the yield of melanomas, most of which were thin, was considerably high and the workload was acceptable. This compares favorably to experiences where dermatologists were involved directly without a filter work by general practitioners.

Monosodium Glutamate Toxicity and the Possible Protective Role of L–Carnitine

2018 ◽  
Vol 6 (1) ◽  
pp. 45-56
Author(s):  
Lalrinzuali Sailo ◽  
◽  
Meesala Krishna Murthy ◽  
Khandayataray Pratima ◽  
Vikas Kumar Roy ◽  
...  
Keyword(s):  
Human Subjects ◽  
Monosodium Glutamate ◽  
Essential Amino Acids ◽  
Protective Role ◽  
Glutamate Toxicity ◽  
Common Salt ◽  
Genotoxic Effects ◽  
Naturally Occurring ◽  
Flavour Enhancer

Monosodium glutamate is naturally available non-essential amino acids, which found in naturally occurring foods and used as flavour enhancer worldwide. Monosodium glutamate is believed to be linked with diverse health problems. The aim of the study was toxic effects of monosodium glutamate (MSG) and the protective role of L-carnitine, light on the available literature from last 25 years about diverse toxicity studies which had been carried out on animal and human models. Google scholar, NCBI, PUBMED, EMBASE, Wangfang databases, and Web of Science databases were used to retrieve the available studies. MSG was linked with deleterious effects particularly in animals including induction of obesity, diabetes, hepatotoxic, neurotoxic and genotoxic effects showed in Literature. Few reports revealed increased hunger, food intake, and obesity in human subjects due to MSG consumption. Hepatotoxic, neurotoxic, and genotoxic effects of monosodium glutamate on humans carried out very limitedly. High consumption of monosodium glutamate may be linked with harmful health effects showed in available literatures. So, it is recommended to use common salt instead of MSG. Furthermore, intensive research is required to explore monosodium glutamate–related molecular and metabolic mechanisms. L-carnitine can protect from Hepatotoxic, neurotoxic, renal impairment and genotoxic effects functionally, biochemically and histopathologically with a corresponding reduction of oxidative stress.

scholarly journals The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage

1999 ◽  
Vol 27 (16) ◽  
pp. 3276-3282 ◽  
Author(s):  
P. P. H. Van Sloun ◽  
J. G. Jansen ◽  
G. Weeda ◽  
L. H. F. Mullenders ◽  
A. A. van Zeeland ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Embryonic Stem Cells ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Embryonic Stem ◽  
Genotoxic Effects ◽  
Nucleotide Excision

scholarly journals A Potential Role and Contribution of Androgens in Placental Development and Pregnancy

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 644
Author(s):  
Agata M. Parsons ◽  
Gerrit J. Bouma
Keyword(s):  
Fetal Development ◽  
Fetal Loss ◽  
Membrane Receptors ◽  
Placental Development ◽  
Placental Function ◽  
Fetal Physiology ◽  
Estrogen Synthesis ◽  
And Function ◽  
Pregnancy Disorders

Successful pregnancy requires the establishment of a highly regulated maternal–fetal environment. This is achieved through the harmonious regulation of steroid hormones, which modulate both maternal and fetal physiology, and are critical for pregnancy maintenance. Defects in steroidogenesis and steroid signaling can lead to pregnancy disorders or even fetal loss. The placenta is a multifunctional, transitory organ which develops at the maternal–fetal interface, and supports fetal development through endocrine signaling, the transport of nutrients and gas exchange. The placenta has the ability to adapt to adverse environments, including hormonal variations, trying to support fetal development. However, if placental function is impaired, or its capacity to adapt is exceeded, fetal development will be compromised. The goal of this review is to explore the relevance of androgens and androgen signaling during pregnancy, specifically in placental development and function. Often considered a mere precursor to placental estrogen synthesis, the placenta in fact secretes androgens throughout pregnancy, and not only contains the androgen steroid nuclear receptor, but also non-genomic membrane receptors for androgens, suggesting a role of androgen signaling in placental function. Moreover, a number of pregnancy disorders, including pre-eclampsia, gestational diabetes, intrauterine growth restriction, and polycystic ovarian syndrome, are associated with abnormal androgen levels and androgen signaling. Understanding the role of androgens in the placenta will provide a greater understanding of the pathophysiology of pregnancy disorders associated with androgen elevation and its consequences.

scholarly journals The pleiotropic role of circular and long non‐coding RNAs in cutaneous melanoma

2021 ◽  
Author(s):  
Barbara Montico ◽  
Giorgio Giurato ◽  
Giovanni Pecoraro ◽  
Annamaria Salvati ◽  
Alessia Covre ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Non Coding Rnas

scholarly journals Mass Spectrometry-Based Proteomic Characterization of Cutaneous Melanoma Ectosomes Reveals the Presence of Cancer-Related Molecules

2020 ◽  
Vol 21 (8) ◽  
pp. 2934 ◽  
Author(s):  
Magdalena Surman ◽  
Sylwia Kędracka-Krok ◽  
Dorota Hoja-Łukowicz ◽  
Urszula Jankowska ◽  
Anna Drożdż ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Content ◽  
Cell Lines ◽  
Cutaneous Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Starting Point ◽  
Novel Biomarkers

Cutaneous melanoma (CM) is an aggressive type of skin cancer for which effective biomarkers are still needed. Recently, the protein content of extracellular vesicles (ectosomes and exosomes) became increasingly investigated in terms of its functional role in CM and as a source of novel biomarkers; however, the data concerning the proteome of CM-derived ectosomes is very limited. We used the shotgun nanoLC–MS/MS approach to the profile protein content of ectosomes from primary (WM115, WM793) and metastatic (WM266-4, WM1205Lu) CM cell lines. Additionally, the effect exerted by CM ectosomes on recipient cells was assessed in terms of cell proliferation (Alamar Blue assay) and migratory properties (wound healing assay). All cell lines secreted heterogeneous populations of ectosomes enriched in the common set of proteins. A total of 1507 unique proteins were identified, with many of them involved in cancer cell proliferation, migration, escape from apoptosis, epithelial–mesenchymal transition and angiogenesis. Isolated ectosomes increased proliferation and motility of recipient cells, likely due to the ectosomal transfer of different cancer-promoting molecules. Taken together, these results confirm the significant role of ectosomes in several biological processes leading to CM development and progression, and might be used as a starting point for further studies exploring their diagnostic and prognostic potential.

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