Flaxseed Does Not Enhance the Estrogenic Effect of Low-Dose Estrogen Therapy on Markers of Uterine Health in Ovariectomized Rats

Sacco, Sandra M.; Jiang, Jessica M Y; Thompson, Lilian U.; Ward, Wendy E.

doi:10.1089/jmf.2011.0314

Cited by 8 publications

(3 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… ✓ Activity; – No Activity; [1] Rose and Connolly ( 1989 ); [2] Liu et al ( 2004 ); [3] Brooks et al ( 2004 ); [4] Colli et al ( 2012 ); [5] Sacco et al ( 2012 ) …”

Section: Comparison Of Mechanistic Potencies To Clinical Endpointsmentioning

confidence: 99%

Human-relevant potency threshold (HRPT) for ERα agonism

Borgert¹,

Matthews

Baker

2018

Arch Toxicol

View full text Add to dashboard Cite

The European Commission has recently proposed draft criteria for the identification of endocrine disrupting chemicals (EDCs) that pose a significant hazard to humans or the environment. Identifying and characterizing toxic hazards based on the manner by which adverse effects are produced rather than on the nature of those adverse effects departs from traditional practice and requires a proper interpretation of the evidence regarding the chemical’s ability to produce physiological effect(s) via a specific mode of action (MoA). The ability of any chemical to produce a physiological effect depends on its pharmacokinetics and the potency by which it acts via the various MoAs that can lead to the particular effect. A chemical’s potency for a specific MoA—its mechanistic potency—is determined by two properties: (1) its affinity for the functional components that comprise the MoA, i.e., its specific receptors, enzymes, transporters, transcriptional elements, etc., and (2) its ability to alter the functional state of those components (activity). Using the agonist MoA via estrogen receptor alpha, we illustrate an empirical method for determining a human-relevant potency threshold (HRPT), defined as the minimum level of mechanistic potency necessary for a chemical to be able to act via a particular MoA in humans. One important use for an HRPT is to distinguish between chemicals that may be capable of, versus those likely to be incapable of, producing adverse effects in humans via the specified MoA. The method involves comparing chemicals that have different ERα agonist potencies with the ability of those chemicals to produce ERα-mediated agonist responses in human clinical trials. Based on this approach, we propose an HRPT for ERα agonism of 1E-04 relative to the potency of the endogenous estrogenic hormone 17β-estradiol or the pharmaceutical estrogen, 17α-ethinylestradiol. This approach provides a practical way to address Hazard Identification according to the draft criteria for identification of EDCs recently proposed by the European Commission.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2186-z) contains supplementary material, which is available to authorized users.

show abstract

“… ✓ Activity; – No Activity; [1] Rose and Connolly ( 1989 ); [2] Liu et al ( 2004 ); [3] Brooks et al ( 2004 ); [4] Colli et al ( 2012 ); [5] Sacco et al ( 2012 ) …”

Section: Comparison Of Mechanistic Potencies To Clinical Endpointsmentioning

confidence: 99%

Human-relevant potency threshold (HRPT) for ERα agonism

Borgert¹,

Matthews

Baker

2018

Arch Toxicol

View full text Add to dashboard Cite

show abstract

“…There are only two reports concerning flaxseed influence on female reproductive organs besides the ovary. Sacco et al 46 observed the histomorphological changes in uteri of rats fed with flaxseed, similar to the changes induced by oestrogen, indicating uterine activation and growth. In the experiments of Vlckova et al 36 , the dietary flaxseed increased the thickness of the endometrium and myometrium in mice uteri.…”

Section: Effects On Female Reproductive Processesmentioning

confidence: 81%

Influence of Flaxseed (Linum usitatissimum) on Female Reproduction

Sirotkin

2023

Planta Med

View full text Add to dashboard Cite

This review describes the chemical composition of flaxseed (Linum usitatissimum) and its general health effects, as well as the currently available knowledge concerning its action on the female reproductive state, functions on the ovary and ovarian cells and reproductive hormones, as well as possible constituents and extra- and intracellular mediators mediating its effects on female reproductive processes. Flaxseed contains a number of biologically active molecules, which, acting through multiple signalling pathways, can determine numerous physiological, protective and therapeutic effects of flaxseed. The available publications demonstrate the action of flaxseed and its constituents on the female reproductive system – ovarian growth, follicle development, the resulting puberty and reproductive cycles, ovarian cell proliferation and apoptosis, oo- and embryogenesis, hormonal regulators of reproductive processes and their dysfunctions. These effects can be determined by flaxseed lignans, alpha-linolenic acid and their products. Their actions can be mediated by changes in general metabolism, metabolic and reproductive hormones, their binding proteins, receptors and several intracellular signalling pathways, including protein kinases, transcription factors regulating cell proliferation, apoptosis, angiogenesis and malignant transformation. Flaxseed and its active molecules are found potentially useful for improving farm animal reproductive efficiency and treatment of polycystic ovarian syndrome and ovarian cancer.

show abstract

“…observed in this study may be due to the timing of OVX. Although the time points in our study are similar to those commonly used in OVX rat studies of PUFA interventions and long bone health [63,64,65], OVX at three months of age causes a premature switch to bone remodeling from normal growth [66]. Therefore, for future study of the alveolar bone, OVX after three months of age may be necessary to limit the disruption to normal trabecular growth and development that may still be occurring at the mandible.…”

Section: Discussionmentioning

confidence: 99%

Providing Flaxseed Oil but Not Menhaden Oil Protects against OVX Induced Bone Loss in the Mandible of Sprague-Dawley Rats

Longo

Ward

2016

Nutrients

View full text Add to dashboard Cite

Higher intakes of polyunsaturated fatty acids (PUFA) are associated with benefits at several skeletal sites in postmenopausal women and in rodent models, but the effect of PUFA-containing oils on tooth-supporting alveolar bone of the mandible has not been studied. Moreover, direct comparison of the effect of flaxseed oil (a source of alpha-linolenic acid (ALA)) and menhaden oil (a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) is unknown. One-month old female Sprague-Dawley rats (n = 48) were randomized to and fed a diet containing flaxseed oil or menhaden oil from one to six months of age. At three months of age, rats were randomized to receive SHAM or ovariectomy (OVX) surgery (n = 12/diet). The inter-radicular septum below the first molar of the mandible was imaged at 6 months of age (study endpoint) using micro-computed tomography (μCT) at a resolution of 9 μm. As expected, OVX significantly reduced percent bone volume (BV/TV), connectivity density (Conn. D.), trabecular number (Tb. N.), and increased trabecular separation (Tb. Sp.) compared to SHAM rats (p < 0.001). However, post hoc analysis revealed these differences were present in rats fed menhaden oil but not those fed flaxseed oil. These results suggest that providing flaxseed oil, possibly through its high ALA content, provides protection against the OVX-induced alveolar bone loss in rats.

show abstract

Flaxseed Does Not Enhance the Estrogenic Effect of Low-Dose Estrogen Therapy on Markers of Uterine Health in Ovariectomized Rats

Cited by 8 publications

References 31 publications

Human-relevant potency threshold (HRPT) for ERα agonism

Human-relevant potency threshold (HRPT) for ERα agonism

Influence of Flaxseed (Linum usitatissimum) on Female Reproduction

Providing Flaxseed Oil but Not Menhaden Oil Protects against OVX Induced Bone Loss in the Mandible of Sprague-Dawley Rats

Contact Info

Product

Resources

About