Cell Proliferation of Estrogen-Sensitive Cells: The Case for Negative Control*

Soto, Ana M.; Sonnenschein, Carlos

doi:10.1210/edrv-8-1-44

Cited by 135 publications

(46 citation statements)

References 64 publications

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“…But at high 10 μM concentration, AD was not able to suppress adipogenesis and adipocyte numbers were back to the control level, showing a biphasic dose-response. This type of biphasic regulation by a sex steroid (androstenedione) was not unusual, as biphasic regulation of cell proliferation had already been reported for estrogen in MCF-7 breast cancer cell line [24] and for androgen in LNCaP prostate cancer cell line [25] [26]. When adipogenic experiments were repeated in the presence of AR antagonist bicalutamide, there was a decrease in myogenesis and increase in adipogenesis in a dose-dependent manner, indicating that AD action was mediated through AR.…”

Section: Discussionsupporting

confidence: 72%

Effect of Androstenedione on Adipogenesis in Murine C3H10T1/2 Mesenchymal Cells

Ramaraj

Artaza²,

Sinha‐Hikim³

et al. 2015

OJEMD

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Clinical trials of weak androgen androstenedione (AD) administered at a high concentration, showed an increase in muscle mass in men like strong androgens testosterone (T) and dihydrotestosterone (DHT), but did not show any inhibitory effect on fat mass unlike strong androgens. This observation prompted us to check the in-vitro effect of AD on adipogenesis using mouse mesenchymal multipotent cells (C3H10T1/2), which can differentiate into both myoblasts and adipocytes. Results indicated that AD inhibited adipogenesis at 10 nM, 100 nM and 1 μM concentrations, but not at 10 μM concentration. AD did not inhibit adipogenesis at 10 μM concentration and also did not inhibitmyogenesis at 10 μM concentration. Addition of bicalutamide, an androgen receptor (AR) antagonist decreased myogenesis and increased adipogenesis, indicating that the effect of AD was mediated through AR. Another weak androgen dehydroepiandrosterone (DHEA) also showed the same pattern of adipogenesis in 10T1/2 cells. AD also showed a similar pattern of adipogenesis in 3T3-L1 preadipocyte cells. Thus, the in-vitro results of AD on adipogenesis correlated with the in-vivo results of AD on fat-mass from clinical trials and suggested a possible difference in biological action between weak androgens (AD, DHEA) and strong androgens (T, DHT) on adipogenesis. Since the biological action of AD was mediated through AR, this physiological difference onadipogenesis could be due to the nature (partial agonist/antagonist) of AD binding to AR.

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Section: Discussionsupporting

confidence: 72%

Effect of Androstenedione on Adipogenesis in Murine C3H10T1/2 Mesenchymal Cells

Ramaraj

Artaza²,

Sinha‐Hikim³

et al. 2015

OJEMD

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“…A major unanswered question is whether estrogen action on bone in vivo is direct or indirect (4,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). It has been suggested that in vivo estrogen promotes the systemic production of growth factors, so-called estromedins, or the removal of growth inhibitors, estrocolyons, elsewhere in the body (42). However, the findings presented here strongly' suggest that estrogen acts directly on bone.…”

Section: Discussionmentioning

confidence: 77%

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

Takano‐Yamamoto

Rodan

1990

Proc. Natl. Acad. Sci. U.S.A.

163

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High-affinity nuclear binding sites for 17 (3-estradiol (17(3E2) were recently found in bone cells; however, the mechanism by which estrogen exerts its effect on bone in vivo is still unknown. To study if estrogen acts on bone directly, we used an experimental model in which test substances are infused locally into rat femur trabecular bone. SpragueDawley rats weighing 150-160 g were ovariectomized (OVX) and 14 days later a polyethylene tube (1 mm in diameter) connected to an Alzet osmotic minipump was implanted into the distal femur 9 mm from the joint. 17fiE2 (24 pl/day at 0.01-1 nM), 17a-estradiol (17aE2) (24 pl/day at 1 nM), or phosphatebuffered saline (NaCl, 8 g/liter; KCI, 0.2 g/liter; KH2PO4, 0.2 g/liter; Na2HPO4-7H2O, 2.16 g/liter) was infused for 8 days.The contralateral limb remained intact. Animals were sacrificed and bones were examined by histomorphometry. Ovariectomy caused a 50% loss in trabecular bone volume (TBV) in the secondary spongiosa (from 20.3% ± 1.7% to 9.6% + 1.1%; mean ± SEM), a 2-fold increase in osteoclast number (to 4.0 ± 0.4 per mm), a 3-fold increase in relative resorption surfaces (to 24.8% ± 2.9%), a 9-fold increase in osteoblast number (to 11.3 ± 2.1 per mm), and an 8-fold increase in relative osteoid surface (to 9.6% ± 1.7%). The local infusion of 17fiE2 for 8 days into OVX rats (t) restored the TBV dose dependently to 75% and 85% of control (non-OVX) levels, at 0.1 nM and 1 nM 17(3E2, respectively; (it) decreased osteoclast number and the relative resorption surface to control (non-OVX) levels; and (iii) further increased osteoblast number and the relative osteoid surface dose dependently (by 5-fold at 1 nM 173E2). Phosphate-buffered saline infusion was without effect.Infusion of 17ciE2 had no effect on TBV, osteoclast number, or resorption surface but increased slightly the osteoblast number and the osteoid surface. Its potency was 1/100 that of 1713E2. The local infusion of 17fiE2 or 17aE2 had no effect on body or uterine weight. We conclude from these rmdings that estrogen delivered directly to the bone of OVX rats in vivo at 2.4 and 24 fmol/day acted locally to inhibit bone resorption and stimulate bone formation.About 50 years ago, Albright et al.(1) suggested a link between postmenopausal osteoporosis and estrogen deficiency. The lack of estrogen is associated with increased bone remodeling rates, accelerated bone loss, and a negative calcium balance (2). Estrogen replacement therapy decreases bone turnover and the rate ofbone resorption and reduces the occurrence of fractures in postmenopausal osteoporosis. However, the mechanism by which estrogen exerts its effects on bone is still unknown (3,4 2172The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…In addition to cell proliferation, other markers of estrogenic activity, such as the PgR assay and pS2 assay in MCF-7 cells, are adequate for assessing estrogenicity in humans. Cell proliferation assays are more sensitive than those that induce gene products (1,(29)(30)(31) Figure 3). The analysis of the interaction of E-SCREEN xenoestrogens in the mixtures of three and ididate for four chemicals indicates that the effect of indard of the mixture is 2-to 3-fold higher than the ells at the expected effect, assuming simple additivity.…”

Section: Discussionmentioning

confidence: 99%

Developing a marker of exposure to xenoestrogen mixtures in human serum.

Soto

Fernández

Luizzi

et al. 1997

Environ Health Perspect

103

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It has been hypothesized that environmental estrogens may play a role in the increasing incidence of breast cancer, testicular cancer, and other problems of the reproductive system. While a single causal agent can be identified in cases in which humans have had occupational exposures, wildlife showing signs of reproductive damage have usually been exposed to a combination of endocrine disruptors that may act cumulatively. The development of appropriate biomarkers of cumulative exposure, and their measurement at developmental points where exposure is critical, are required to test the environmental estrogen hypothesis. Measuring levels of each of the xenoestrogens in blood is a better approximation of real exposure at the target organ level than inferring cumulative exposure by estimating from mass balance of dietary levels. However, the cumulative estrogenicity of mixtures cannot be directly concluded from individual xenoestrogen plasma levels. Two approaches may be used to assess total load: a) the development of methods to study mixtures of these xenoestrogens, to quantify their cumulative effects, and to begin to understand their interactions (i.e., additivity, synergy, antagonism, or independent action), so that plasma concentrations may be translated into units of activity such as "estradiol equivalents"; and b) the development of methods to separate xenoestrogens from ovarian estrogens in blood and to directly measure the estrogenic activity of the xenoestrogen extract using a bioassay. The cumulative activity may be used as a marker of exposure to xenoestrogens. This article reports the development of a method to extract and separate xenoestrogens from ovarian estrogens using human serum as a source, followed by using a bioassay for determination of the cumulative xenoestrogen load as "estradiol equivalents."

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Cell Proliferation of Estrogen-Sensitive Cells: The Case for Negative Control*

Cited by 135 publications

References 64 publications

Effect of Androstenedione on Adipogenesis in Murine C3H10T1/2 Mesenchymal Cells

Effect of Androstenedione on Adipogenesis in Murine C3H10T1/2 Mesenchymal Cells

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

Developing a marker of exposure to xenoestrogen mixtures in human serum.

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