Estrogens as arbiters of sex-specific and reproductive cycle-dependent opioid analgesic mechanisms

Gintzler, Alan R.; Storman, Emiliya M.; Liu, Nai-Jiang

doi:10.1016/bs.vh.2019.06.002

Cited by 4 publications

(2 citation statements)

References 111 publications

(123 reference statements)

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“…IL-6 can also promote osteoclastic activity and bone loss by activating the osteoprotegerin/receptor activator of nuclear factor kappa B ligand/ receptor activator of the nuclear factor kappa B (OPG/ RANKL/RANK) system, leading to osteoporosis [23]. In several animal models of chronic inflammation, estrogen can inhibit bone resorption and inflammation, reducing inflammation-mediated pain responses and the occurrence of neuroinflammatory diseases [24]. Our present findings are compatible with those of previous studies.…”

Section: Discussionsupporting

confidence: 91%

Circulating IGFBP-3 and Interleukin 6 as Predictors of Osteoporosis in Postmenopausal Women: A Cross-Sectional Study

Shi

Jiang

Rao

et al. 2023

Mediators of Inflammation

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Objective. To explore the relationship between circulating IGFBP-3, IL-6, and bone mineral density and the potential diagnostic role of circulating IGFBP-3 and IL-6 in postmenopausal women with osteoporosis. Methods. Eighty-five postmenopausal women at Soochow University’s First Affiliated Hospital, Osteoporosis and Menopause Clinics, were recruited. Forty-five of 85 women were diagnosed with osteoporosis. Circulating IL-6, PTH, 1,25(OH)2D3, osteocalcin (OST), IGF-1, IGFBP-3, and bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) were measured in 40 ordinary and 45 osteoporotic women. A simple regression analysis calculated the correlation between age, BMD, IL-6, and IGFBP-3. Multiple stepwise regression analyses were conducted to determine which variables were independently related to BMD. The potential role of IGFBP-3 and IL-6 in the diagnosis of postmenopausal osteoporosis was predicted using the area under the receiver operating characteristic curve (ROC, AUC). Results. Age, years since menopause, and circulating IL-6, PTH, and IGFBP-3 were significantly higher in the osteoporosis group compared to the normal group. Osteoporotic women had substantially lower BMDs of the LS and FN than normal women. Age-related increases were found for IGFBP-3 and IL-6, whereas age-related decreases were observed for LS/FN BMD. IGFBP-3 and IL-6 were both negatively correlated with LS and FN BMD. Stepwise multiple regression analysis showed that IGFBP-3 and IL-6 were strong predictors of BMD in postmenopausal women. AUC cut-off values (IGFBP-3: 3.65, IL-6: 0.205) were best evaluated for the diagnosis of postmenopausal women with osteoporosis, and the AUC for circulating IGFBP-3 and IL-6 were 0.706 (95% CI 0.594–0.818) and 0.685 (95% CI 0.571–0.798), respectively. Conclusion. In this cross-sectional study of postmenopausal women, IGFBP-3 and IL-6 were negatively related to BMD. Circulating IGFBP-3 and IL-6 might be essential predictors of postmenopausal osteoporosis and can help predict osteoporotic fracture.

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Section: Discussionsupporting

confidence: 91%

Circulating IGFBP-3 and Interleukin 6 as Predictors of Osteoporosis in Postmenopausal Women: A Cross-Sectional Study

Shi

Jiang

Rao

et al. 2023

Mediators of Inflammation

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“…This may lessen pain responses that are triggered by inflammation and prevent the development of neuroinflammatory diseases. However, the exact mechanism is not fully understood [7].…”

Section: Effect Of Oestrogen On Postmenopausal Osteoporosismentioning

confidence: 99%

The effectiveness of estrogen therapy and aerobic exercise combined with resistance training therapy in postmenopausal womens osteoporosis

Hu,

Xiang,

Zhang

2023

TNS

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Postmenopausal osteoporosis (PMOP) usually happens five to ten years following a womans menopause, and some women over 50 in China suffer from PMOP. Hormone replacement therapy (HRT) and aerobics combined with resistance training are the two promising osteoporosis interventions, but few studies have compared their efficacy. The mechanisms by which exercise treatment and hormone replacement therapy affect bone mineral density (BMD) are examined in this review and other health parameters in postmenopausal osteoporosis patients. As studied in this paper, estrogen improves osteoporosis. However, risks such as venous thromboembolism limit the long-term use of HRT. In terms of exercise therapy, a direct comparison of aerobic exercise combined with resistance exercise and HRT showed that supervised exercise improved BMD more than HRT and that exercise also boosted metabolism and avoided the risks of HRT. In conclusion, aerobic and resistance training provides a safer alternative to HRT for managing postmenopausal osteoporosis, and further studies should optimize exercise regimens.

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Aging is associated with sex-specific alteration in the expression of genes encoding for neuroestradiol synthesis and signaling proteins in the mouse trigeminal somatosensory input

Bautista-Abad,

García-Magro,

Pinto-Benito

et al. 2024

GeroScience

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Pain perception is influenced by sex and aging, with previous studies indicating the involvement of aromatase, the estradiol synthase enzyme, in regulating pain perception. Previous research has established the presence of aromatase in dorsal root ganglia sensory neurons and its role in modulating pain perception. The present study aims to explore the implications of aging and sex on the expression of aromatase and estrogen receptors in the trigeminal ganglion. The study examined mRNA levels of aromatase, ERs, and the androgen receptor (AR) in the trigeminal ganglion of 3-month-old and 27-month-old male and female mice, as well as 3-month-old mice from the four-core genotype (FCG) transgenic model. The latter facilitates the assessment of gonadal hormone and sex chromosome implications for sex-specific traits. Aromatase localization in the ganglion was further assessed through immunohistochemistry. Aromatase immunoreactivity was observed for the first time in sensory neurons within the trigeminal ganglion. Trigeminal ganglion gene expressions were detected for aromatase, ERs, and AR in both sexes. Aromatase, ERβ, and GPER gene expressions were higher in young males versus young females. Analyses of the FCG model indicated that sex differences depended solely on gonadal sex. The aging process induced an enhancement in the expression of aromatase, ERs, and AR genes across both sexes, culminating in a reversal of the previously observed gender-based differences. the potential impact of estrogen synthesis and signaling in the trigeminal ganglion on age and sex differences warrants consideration, particularly in relation to trigeminal sensory functions and pain perception. Graphical abstract Age and gonadal sex influence ERs, AR, and ARO levels in the trigeminal ganglion. Although somatosensory perception shows a decline in the elderly, the incidence of trigeminal neuralgia intensifies in aged adults and is predominantly prevalent in women relative to men. The increased expression of aromatase and estrogen receptors in aged female animals suggests that the modulatory influence that neuroestradiol exerts over the trigeminal somatosensory input, inclusive of pain, undergoes changes in elderly male and female individuals in a sex-specific manner.

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Estrogens as arbiters of sex-specific and reproductive cycle-dependent opioid analgesic mechanisms

Cited by 4 publications

References 111 publications

Circulating IGFBP-3 and Interleukin 6 as Predictors of Osteoporosis in Postmenopausal Women: A Cross-Sectional Study

Circulating IGFBP-3 and Interleukin 6 as Predictors of Osteoporosis in Postmenopausal Women: A Cross-Sectional Study

The effectiveness of estrogen therapy and aerobic exercise combined with resistance training therapy in postmenopausal womens osteoporosis

Aging is associated with sex-specific alteration in the expression of genes encoding for neuroestradiol synthesis and signaling proteins in the mouse trigeminal somatosensory input

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