Oestrogen formation from androstenedione in human bone

Schweikert, Hans-Udo; Wolf, Lutz; Romalo, G.

doi:10.1111/j.1365-2265.1995.tb01890.x

Cited by 65 publications

(17 citation statements)

References 34 publications

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“…This is in part explained by the direct effect of oestrogen on the cell fate of MSCs towards either osteoblasts or adipocytes [101,102]. Of note, regulation of aromatase activity may provide another level of regulation of bone mass by marrow adipocyets because aromatase is highly expressed in bone marrow stromal cells [103][104][105][106][107][108]. Hence, it is possible that locally produced androgens and oestrogens in marrow adipocytes can exert regulatory actions on bone marrow cells including osteogenic cells.…”

Section: Marrow Fat and Osteoporosismentioning

confidence: 99%

New insights into osteoporosis: the bone–fat connection

Kawai

Paula

Rosen

2012

Journal of Internal Medicine

235

179

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Osteoporosis and obesity are chronic disorders that are increasing in prevalence. The pathophysiology of these diseases is multifactorial and includes genetic, environmental and hormonal determinants. Long considered as distinct disorders that rarely are found in the same individual, emerging evidence from basic and clinical studies support an important interaction between adipose tissue and the skeleton. Adiposity can influence bone remodeling through three possible mechanisms including secretion of cytokines that directly target bone, adipokines that influence the central nervous system thereby changing sympathetic impulses to bone, and paracrine influences on adjacent skeletal cells. This review will focus on our current understanding of bone-fat interactions and the clinical implications of recent studies linking obesity to osteoporosis.

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Section: Marrow Fat and Osteoporosismentioning

confidence: 99%

New insights into osteoporosis: the bone–fat connection

Kawai

Paula

Rosen

2012

Journal of Internal Medicine

235

179

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“…Frisch et al reported the production of estrogens from androgens in fatty marrow extracts isolated from femoral heads and iliac crests obtained from female subjects undergoing orthopaedic surgery [ 35 ]. Schweikert and Romalo demonstrated aromatase enzymatic activity and estrogen production in extracts prepared from ground trabecular bone tissues isolated from specimens obtained following hip replacement surgeries in male and female patients, and reported that the addition of aromatase inhibitors to these extracts inhibited estrogen production [ 36 ]. Sasano et al evaluated aromatase immunoreactivity and RNA expression via in situ hybridization and RT-PCR in bone tissue specimens including ribs, vertebrae and femurs from a series of 28 male and female patients undergoing orthopaedic surgery [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells

et al. 2017

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BackgroundApproximately 70% of all breast cancers express the estrogen receptor, and are regulated by estrogen. While the ovaries are the primary source of estrogen in premenopausal women, most breast cancer is diagnosed following menopause, when systemic levels of this hormone decline. Estrogen production from androgen precursors is catalyzed by the aromatase enzyme. Although aromatase expression and local estrogen production in breast adipose tissue have been implicated in the development of primary breast cancer, the source of estrogen involved in the regulation of estrogen receptor-positive (ER+) metastatic breast cancer progression is less clear.MethodsBone is the most common distant site of breast cancer metastasis, particularly for ER+ breast cancers. We employed a co-culture model using trabecular bone tissues obtained from total hip replacement (THR) surgery specimens to study ER+ and estrogen receptor-negative (ER-) breast cancer cells within the human bone microenvironment. Luciferase-expressing ER+ (MCF-7, T-47D, ZR-75) and ER- (SK-BR-3, MDA-MB-231, MCF-10A) breast cancer cells were cultured directly on bone tissue fragments or in bone tissue-conditioned media, and monitored over time with bioluminescence imaging (BLI). Bone tissue-conditioned media were generated in the presence vs. absence of aromatase inhibitors, and testosterone. Bone tissue fragments were analyzed for aromatase expression by immunohistochemistry.ResultsER+ breast cancer cells were preferentially sustained in co-cultures with bone tissues and bone tissue-conditioned media relative to ER- cells. Bone fragments analyzed by immunohistochemistry revealed expression of the aromatase enzyme. Bone tissue-conditioned media generated in the presence of testosterone had increased estrogen levels and heightened capacity to stimulate ER+ breast cancer cell proliferation. Pretreatment of cultured bone tissues with aromatase inhibitors, which inhibited estrogen production, reduced the capacity of conditioned media to stimulate ER+ cell proliferation.ConclusionsThese results suggest that a local estrogen signaling axis regulates ER+ breast cancer cell viability and proliferation within the bone metastatic niche, and that aromatase inhibitors modulate this axis. Although endocrine therapies are highly effective in the treatment of ER+ breast cancer, resistance to these treatments reduces their efficacy. Characterization of estrogen signaling networks within the bone microenvironment will identify new strategies for combating metastatic progression and endocrine resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0910-x) contains supplementary material, which is available to authorized users.

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“…E2 increases through aromatization of T during T replacement . Aromatase has been demonstrated in the testes, brain , adipose tissue , muscle , hair , bone , and vascular tissue . Eighty percent of circulating E2 is derived from peripheral aromatization of testicular or adrenal androgens.…”

Section: Discussionmentioning

confidence: 99%

Coadministration of Anastrozole Sustains Therapeutic Testosterone Levels in Hypogonadal Men Undergoing Testosterone Pellet Insertion

Mechlin

Frankel

McCullough

2014

The Journal of Sexual Medicine

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Introduction Current U.S. Food and Drug Administration–approved therapies for hypogonadism involve testosterone (T) replacement. Testosterone pellets (TP) require a minor office procedure every 3 to 4 months. The need for repeated insertions increases the likelihood of a complication. Anastrozole (AZ) is an aromatase inhibitor that has been used off-label for the treatment of male hypogonadism. AZ increases T levels by lowering serum estradiol (E2) levels and increasing gonadotropin (GTP) levels. Aim We hypothesized that the concomitant use of AZ with TP insertions would sustain therapeutic T levels and increase the interval between TP insertions. Methods Men treated with TP for hypogonadism at an academic center were offered AZ (1 mg/day) at the time of TP reinsertion as a way of potentially decreasing the frequency of TP insertions. Total T (TT), free T (FT), sex hormone binding globulin, E2, luteinizing hormone (LH), and follicle-stimulating hormone FSH levels were obtained prior to T replacement and at 6 and 15 weeks from TP insertion. Men were re-implanted at 16 weeks if their TT levels were less than 350 ng/dL and their symptoms recurred. We retrospectively reviewed our records of men who underwent TP, TP, and AZ from 2011 to 2012. Demographics, TT, FT, LH, FSH, and E2 levels were recorded. Data were analyzed with anova and a Tukey's test. Main Outcome Measure TT level at 6, 15, or >15 weeks from TP insertion. Results Thirty-eight men with 65 insertions were analyzed. The TP AZ group had significantly higher TT and FT levels than the TP group at >120 days (P < 0.05). The TP group had significantly higher E2 levels at all time points (P < 0.01). GTP levels remained stable in the TP AZ group. Average time to reinsertion in TP AZ was 198 days vs. 128 days in the TP group. Conclusion Men on TP AZ maintain therapeutic T levels longer than men on TP alone and have significantly less GTP suppression.

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Oestrogen formation from androstenedione in human bone

Abstract: Oestrogens formed in human bone may play a physiological role in steroid hormone action in this tissue.

Cited by 65 publications

References 34 publications

New insights into osteoporosis: the bone–fat connection

New insights into osteoporosis: the bone–fat connection

Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells

Coadministration of Anastrozole Sustains Therapeutic Testosterone Levels in Hypogonadal Men Undergoing Testosterone Pellet Insertion

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