Ability of lymphocytes infiltrating breast-cancer tissue to convert androstenedione

Berstein, Lev M.; Порошина, Т. Е.; Zimarina, T. S.; Larionov, Alexey; Коваленко, И. Г.; Uporov, A. V.

doi:10.1002/(sici)1097-0215(19980812)77:4<485::aid-ijc1>3.0.co;2-q

Cited by 6 publications

(6 citation statements)

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“…For example, previous studies in mesenchymal stem cells (MSCs) isolated from post-menopausal women have shown leptin and vitamin D induced aromatase expression and activity [ 32 ]. Several cell types of hematopoietic origin express aromatase including T lymphocytes [ 12 ], B lymphocytes [ 13 , 14 ], and macrophages [ 15 ]—the latter of which also express estrogen receptors [ 17 , 33 ]. Each of these cell types can indirectly regulate the formation and activity of osteoclasts and osteoblasts through the release of soluble factors such as TNFα and RANKL [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mature cells of myeloid lineage include erythrocytes and immune cells such as monocytes, macrophages, neutrophils, basophils, eosinophils, and dendritic cells [ 11 ], while T cells, B cells, and natural killer cells are derived from lymphoid precursors. A number of HSC descendants from both human and murine cells express aromatase, including T lymphocytes [ 12 ], B lymphocytes [ 13 , 14 ], and macrophages [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients

Rubitschung,

Sherwood,

Kapadia

et al. 2024

PLoS ONE

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Estradiol is an important regulator of bone accumulation and maintenance. Circulating estrogens are primarily produced by the gonads. Aromatase, the enzyme responsible for the conversion of androgens to estrogen, is expressed by bone marrow cells (BMCs) of both hematopoietic and nonhematopoietic origin. While the significance of gonad-derived estradiol to bone health has been investigated, there is limited understanding regarding the relative contribution of BMC derived estrogens to bone metabolism. To elucidate the role of BMC derived estrogens in male bone, irradiated wild-type C57BL/6J mice received bone marrow cells transplanted from either WT (WT(WT)) or aromatase-deficient (WT(ArKO)) mice. MicroCT was acquired on lumbar vertebra to assess bone quantity and quality. WT(ArKO) animals had greater trabecular bone volume (BV/TV p = 0.002), with a higher trabecular number (p = 0.008), connectivity density (p = 0.017), and bone mineral content (p = 0.004). In cortical bone, WT(ArKO) animals exhibited smaller cortical pores and lower cortical porosity (p = 0.02). Static histomorphometry revealed fewer osteoclasts per bone surface (Oc.S/BS%), osteoclasts on the erosion surface (ES(Oc+)/BS, p = 0.04) and low number of osteoclasts per bone perimeter (N.Oc/B.Pm, p = 0.01) in WT(ArKO). Osteoblast-associated parameters in WT(ArKO) were lower but not statistically different from WT(WT). Dynamic histomorphometry suggested similar bone formation indices’ patterns with lower mean values in mineral apposition rate, label separation, and BFR/BS in WT(ArKO) animals. Ex vivo bone cell differentiation assays demonstrated relative decreased osteoblast differentiation and ability to form mineralized nodules. This study demonstrates a role of local 17β-estradiol production by BMCs for regulating the quantity and quality of bone in male mice. Underlying in vivo cellular and molecular mechanisms require further study.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients

Rubitschung,

Sherwood,

Kapadia

et al. 2024

PLoS ONE

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“…Part of the samples (non-cultivated cells) went directly through a total RNA isolation procedure (see below) while another part was cultivated for 48 h at 37°C in RPMI-1640 containing 10% fetal calf serum (Gibco), penicillin (100 U/ml), and streptomycin (100 lg/ml). Tumor tissue obtained from 11 breastcancer patients (aged from 42 years to 72 years; nine patients were in the postmenopausal period) was immediately transported on ice to the laboratory and used for lymphocyte isolation (Belldegrun et al 1989;Berstein et al 1998). The majority of collected lymphocyte-containing samples were subjected to immunophenotyping with DAKO antibodies to CD45 and to cytokeratin (the latter was done to discover the possible proportion of tumor epithelial cells in the material; this value was never above 8-10%).…”

Section: Methodsmentioning

confidence: 99%

Aromatase (CYP19) expression in tumor-infiltrating lymphocytes and blood mononuclears

Larionov

et al. 2002

Journal of Cancer Research and Clinical Oncology

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“…Murine splenic T lymphocytes exhibited 5α-reductase, aromatase, 3βHSD, and 17βHSD activity, whereas lower rates of steroid synthesis and no evidence of 17βHSD activity were found in B lymphocytes [73] . Aromatase-dependent conversion of androstenedione further has been shown in infiltrating lymphocytes in breast cancer [99] . Steroidogenic enzyme activity in macrophages and lymphocytes has not been compared directly, although aromatase expression was found to be substantially higher in macrophages than T lymphocytes [100] .…”

Section: Steroidogenic Capacity Of Immune Cellsmentioning

confidence: 99%

An intracrine view of sex steroids, immunity, and metabolic regulation

Rubinow

2018

Molecular Metabolism

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BackgroundOver the past two decades, parallel recognition has grown of the importance of both sex steroids and immune activity in metabolic regulation. More recently, these discrete areas have been integrated in studies examining the metabolic effects of sex steroid immunomodulation. Implicit in these studies has been a traditional, endocrine model of sex steroid delivery from the gonads to target cells, including immune cells. Thus, research to date has focused on the metabolic effects of sex steroid receptor signaling in immune cells. This endocrine model, however, overlooks the extensive capacity of immune cells to generate and metabolize sex steroids, enabling the production of sex steroids for intracrine signaling – that is, sex steroid production for signaling within the cell of origin. Intracrine function allows highly cell-autonomous regulation of sex steroid exposure, and sex steroid secretion by immune cells could confer paracrine signaling effects in neighboring cells within metabolic tissues. In this review, immune cell intracrinology will denote sex steroid production within immune cells for either intracrine or paracrine signaling. This intracrine capacity of immune cells has been well established, and prior work has supported its importance in autoimmune disorders, trauma, and cancer. The potential relevance of immune cell intracrine function to the regulation of energy balance, body weight, body composition, and insulin sensitivity has yet to be explored.Scope of reviewThe following review will detail findings to date regarding the steroidogenic and steroid metabolizing capacity of immune cells, the regulation of immune cell intracrine function, and the biological effects of immune-derived sex steroids, including the clinical relevance of immune cell intracrinology in fields other than metabolism. These findings will serve as the basis for a proposed model of immune cell intracrinology constituting a new frontier in metabolism research.Major conclusionsThe development of highly sensitive mass spectrometric methods for sex steroid measurement and quantitation of metabolic flux now allows unprecedented ability to interrogate sex steroid production, metabolism and secretion by immune cells. Immune cell intracrinology could reveal key mechanisms underlying immune cell-mediated metabolic regulation.

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Ability of lymphocytes infiltrating breast-cancer tissue to convert androstenedione

Cited by 6 publications

References 12 publications

Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients

Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients

Aromatase (CYP19) expression in tumor-infiltrating lymphocytes and blood mononuclears

An intracrine view of sex steroids, immunity, and metabolic regulation

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