Effects of long-term tibolone treatment on nuclear sex steroid hormone receptors and G-protein–coupled estrogen receptor-1 expression in the macaque uterus

Hulchiy, Mariana; Zhang, H; Jm, Cline; Al, Hirschberg; Sahlin, Lena

doi:10.1097/gme.0b013e318230f3be

Cited by 7 publications

(2 citation statements)

References 28 publications

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“…In a study by Coyoy‐Salgado et al, 57 tibolone showed no effect on ERα, although it reduced ERβ in the cortex and hypothalamus but not hippocampus of rats fed a high‐fat diet. In the breast, both receptor types are not modified by tibolone, 58 whereas this compound increases ERα in the uterus 59 . Thus, although tibolone binds to ER, effects on receptor expression may be tissue‐, time‐ or dose‐dependent.…”

Section: Discussionmentioning

confidence: 98%

Tibolone restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis

Mancino

Lima

Roig

et al. 2021

J Neuroendocrinology

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Multiple sclerosis (MS) is an immune‐mediated and degenerating disease in which myelin sheaths are damaged as a result of chronic progressive inflammation of the central nervous system. Tibolone [(7α,17α)‐17‐hydroxy‐7‐methyl‐19‐norpregn‐5(10)‐en‐20‐in‐3‐one], a synthetic estrogenic compound with tissue‐specific actions and used for menopausal hormone therapy, shows neuroprotective and antioxidant properties both in vivo and in vitro. In the present study, we analyzed whether tibolone plays a therapeutic role in experimental autoimmune encephalomyelitis (EAE) mice, a commonly used model of MS. Female C57BL/6 mice were induced with the myelin oligodendrocyte glycoprotein MOG35–55 and received s.c. tibolone (0.08 mg kg–1) injection every other day from the day of induction until death on the acute phase of the disease. Reactive gliosis, Toll like receptor 4 (TLR4), high mobility group box protein 1 (HMGB1), inflammasome parameters, activated Akt levels and myelin were assessed by a real‐time polymerase chain reaction, immunohistochemistry, and western blot analysis. Our findings indicated that, in the EAE spinal cord, tibolone reversed the astrocytic and microglial reaction, and reduced the hyperexpression of TLR4 and HMGB1, as well as NLR family pyrin domain containing 3‐caspase 1‐interleukin‐1β inflammasome activation. At the same time, tibolone attenuated the Akt/nuclear factor kappa B pathway and limited the white matter demyelination area. Estrogen receptor expression was unaltered with tibolone treatment. Clinically, tibolone improved neurological symptoms without uterine compromise. Overall, our data suggest that tibolone may serve as a promising agent for the attenuation of MS‐related inflammation.

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Section: Discussionmentioning

confidence: 98%

Tibolone restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis

Mancino

Lima

Roig

et al. 2021

J Neuroendocrinology

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“…To support this idea, it has been shown that: 1) estrogen receptor α predominates in the endometrium, whereas progesterone receptors A and B do in myometrium [ 20 ] ; 2) tibolone metabolite distribution varies among tissues, for example Δ 4 -tibolone (progestagenic/androgenic) is present in myometrium and vagina, and 3-α-hydroxytibolone (estrogenic) is found in serum from postmenopausal women treated with tibolone [ 21 ] ; and 3) within endometrium, depending on the cell type, tibolone may induce diff erent responses, such as the decrease of estrogen receptor-alpha mRNA and protein in stromal cells, and the induction of progesterone receptor mRNA in glandular cells [ 19 ] . Another plausible explanation to the lack of contractile response to serotonin in the uterine rings is that, besides 5-HTR 2A , tibolone may induce the expression of an inhibitory serotonin receptor subtype, which might counteract the 5-HTR 2A stimulatory eff ect.…”

mentioning

confidence: 88%

Tibolone Induces Serotonin, Estrogen, and Progesterone Receptor Expression but not Contractile Response to Serotonin in the Rat Uterus

et al. 2013

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Most studies on the effect of tibolone on the uterus have focused on the endometrium dismissing the importance of the myometrium. The aim of the present study was to investigate some estrogen-like actions of tibolone in the uterus assessed by: 1) the expression of estrogen, progesterone, and serotonin receptors, and 2) the myometrial contraction induced by serotonin. Estradiol (250 μg), progesterone (50 mg), or testosterone (25 mg) pellets were implanted to ovariectomized rats. Tibolone (0.5 mg/day) was orally administered. An implanted pellet containing vehicle or an equivalent volume of water p.o., were used as controls. Sixty days after beginning the treatments, rats were killed and uterus removed. One horn was processed to evaluate estrogen-alpha, progesterone A and B, and serotonin-2A receptors expression, and the other one was used for studying contraction to serotonin and 60 mM potassium solution. The present data showed that tibolone-induced expression of estrogen, progesterone, and serotonin receptors, but did not induce uterine contractile response to either serotonin or potassium solution. These findings suggest that, in the uterus, tibolone may exert molecular estrogenic actions such as the induction of receptor expression, but not a physiological response as the estrogen-dependent contraction to serotonin.

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Endometrial expression of anti-Müllerian hormone and its type II receptor in women with polycystic ovary syndrome

Paulson

Sahlin

Hirschberg

2020

Reproductive BioMedicine Online

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Effects of long-term tibolone treatment on nuclear sex steroid hormone receptors and G-protein–coupled estrogen receptor-1 expression in the macaque uterus

Cited by 7 publications

References 28 publications

Tibolone restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis

Tibolone restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis

Tibolone Induces Serotonin, Estrogen, and Progesterone Receptor Expression but not Contractile Response to Serotonin in the Rat Uterus

Endometrial expression of anti-Müllerian hormone and its type II receptor in women with polycystic ovary syndrome

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