RESUMEN
BACKGROUND: Uterine leiomyoma is the most widespread benign tumor affecting women of childbearing age. There are still gaps in the understanding of its pathogenesis. Telocytes are unique cells found in more than 50 different locations inside the human body. The functional relationship between cells could clarify the pathogenesis of leiomyomata. Examination of membrane receptors on telocytes could explain their role in fibrosis, oxidative stress, and myometrial contractility. AIM: This research was conducted to assess the density of telocytes in terms of their putative role in leiomyoma formation by focusing on their correlation with the expression of estrogen and progesterone receptors. METHODS: For gross evaluation of uterine tissue samples from leiomyoma, routine histology of adjacent and unaffected myometrium was performed. Immunohistochemical analysis of c-kit, tryptase, CD34, PDGFRα (telocyte-specific), and ER and PRs (estrogen and progesterone receptors) was performed to examine uterine telocytes and the expression of sex steroid receptors. RESULTS: The decline in telocyte density in leiomyoma foci was correlated with high progesterone expression and low estrogen receptor expression. The unchanged myometrium showed the opposite correlation and balance between both steroid hormone receptors. The difference in sex steroid receptor expression is correlated with the density of uterine telocytes, which emphasizes their conductor function. CONCLUSIONS: A reduction in telocyte density and the changes in examined marker expression demonstrate the involvement of telocytes in local homeostasis. The expression of membrane receptors explicitly indicates their functional potential in the human myometrium, focusing attention on contractility and local homeostasis.
Asunto(s)
Congéneres del Estradiol/farmacocinética , Leiomioma/diagnóstico por imagen , Leiomioma/patología , Progesterona/farmacocinética , Telocitos/efectos de los fármacos , Telocitos/fisiología , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/patología , Adulto , Anciano , Congéneres del Estradiol/fisiología , Femenino , Humanos , Persona de Mediana Edad , Polonia , Progesterona/fisiologíaRESUMEN
Fluctuations in the levels of sex steroid hormones begin at menarche and end with menopause in the human female. The association between gingivitis and increases in systemic sex steroids has been extensively reported and the biological mechanisms underlying this florid inflammatory state have been examined over several decades. The purpose of this review is to critically examine the evidence in the literature on the effect of female sex steroids on oral bacterial communities.
Asunto(s)
Congéneres del Estradiol/fisiología , Microbiota/fisiología , Periodoncio/microbiología , Congéneres de la Progesterona/fisiología , Biopelículas , Femenino , Humanos , Menarquia/fisiología , Menopausia/fisiología , Ciclo Menstrual/fisiología , Embarazo/fisiología , Pubertad/fisiologíaRESUMEN
Hypothesizing that rapid estrogen signaling could be modulated from different estrogen receptors with unique localization patterns, a number of groups have attempted to design drug conjugates that target or restrict compounds to specific subcellular compartments. This article will briefly discuss the history of using conjugates to dissect rapid estrogen signaling and different strategies to attempt to target estrogens and antiestrogens to different locations. It will also detail some of the potential issues that can arise with different types of conjugates, using examples drawn from the authors' own work.
Asunto(s)
Congéneres del Estradiol/farmacología , Estrógenos/farmacología , Receptores de Estrógenos/metabolismo , Animales , Congéneres del Estradiol/metabolismo , Congéneres del Estradiol/fisiología , Moduladores de los Receptores de Estrógeno/metabolismo , Moduladores de los Receptores de Estrógeno/farmacología , Estrógenos/metabolismo , Estrógenos/fisiología , Humanos , Receptores de Estrógenos/agonistas , Receptores de Estrógenos/antagonistas & inhibidores , Transducción de SeñalRESUMEN
In experimental autoimmune encephalomyelitis (EAE) and other neurodegenerative diseases, astrocytes play an important role in promoting or attenuating the inflammatory response through induction of different cytokines and growth factors. HuR plays a major role in regulating many of these factors by modulating RNA stability and translational efficiency. Here, we engineered transgenic mice to express HuR in astrocytes using the human glial fibrillary acidic protein promoter and found that female transgenic mice had significantly less clinical disability and histopathological changes in the spinal cord. Ovariectomy prior to EAE induction abrogated the protective effect. Our findings support a role for the astrocyte and posttranscriptional regulation in hormonally-mediated attenuation of EAE.
Asunto(s)
Astrocitos/metabolismo , Proteínas ELAV/biosíntesis , Proteínas ELAV/genética , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/patología , Congéneres del Estradiol/fisiología , Regulación de la Expresión Génica/inmunología , Animales , Astrocitos/inmunología , Astrocitos/patología , Proteínas ELAV/fisiología , Encefalomielitis Autoinmune Experimental/metabolismo , Femenino , Humanos , Ratones , Ratones Transgénicos , Médula Espinal/inmunología , Médula Espinal/metabolismo , Médula Espinal/patologíaRESUMEN
The present study aimed to investigate the changes in the mechanical properties of human muscle and tendon during the menstrual cycle in vivo. The subjects were young healthy women (n=8, age 22.5+/-0.9 years) with a normal menstrual cycle. Cycle phases were divided into the menstrual (when estradiol and progesterone concentrations were low), ovulatory (when estradiol was elevated and progesterone was low), and luteal (when progesterone was elevated). Measurements included maximal isometric voluntary contraction (MVC), muscle activation level (using interpolated twitch method), and tendon properties (using ultrasonography) in knee extensors and plantar flexors. No significant changes in MVC and muscle activation level were found during the menstrual cycle. Similarly, there were no significant differences in the maximal elongation and stiffness of tendons among the three phases. These results suggested that the changes in female steroid hormones during the menstrual cycle did not affect the mechanical properties of human muscle and tendon.
Asunto(s)
Congéneres del Estradiol/fisiología , Contracción Isométrica/fisiología , Ciclo Menstrual/fisiología , Fuerza Muscular/fisiología , Músculo Esquelético/fisiología , Congéneres de la Progesterona/fisiología , Tendones/fisiología , Adulto , Femenino , HumanosRESUMEN
Estrogen has demonstrated neuroprotective properties, which may underlie the observed preventive effect of estrogen-based hormone therapy (HT) against the development of neurodegenerative disorders such as Alzheimer's disease. Deleterious side effects of HT have increased efforts to develop safer compounds that selectively reproduce beneficial estrogen actions. Recently, 4-estren-3 alpha,17 beta-diol (estren) was identified as having estrogen agonist properties in bone, without significantly stimulating growth of reproductive tissues. Here, we examined whether estren parallels the neuroprotective actions of estrogen against beta-amyloid (A beta) in cultured cerebrocortical neurons. Estren increased neuronal viability to a similar extent to that observed with 17 beta-estradiol (E2) and 17 alpha-estradiol. As we previously reported for E2, estren rapidly increased PKC activity, and PKC inhibition prevented estren neuroprotection. In contrast, the estrogen receptor antagonist ICI 182,780 blocked E2, but not estren neuroprotection. Our results indicate that estren-induced activation of rapid cell signaling pathways protects cultured neurons from A beta toxicity.
Asunto(s)
Congéneres del Estradiol/fisiología , Estrenos/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , RatasRESUMEN
The ongoing development and gradual availability of the new anti-androgens hold exciting clinical implications for the future. The biosynthesis and interchangeability of the sex steroids, the roles of the ovaries and adrenals and the value and interpretation of biochemical assays in clinical practice are briefly discussed. Because the anti-androgens are used primarily for seborrhoea/acne/hirsutism/oligomenorrhoea, the pathophysiological basis of this socially debilitating syndrome is discussed. The classification of the anti-androgens, their indications, side-effects, dosage schemes and results of treatment are reviewed. Finally, a summary of a possible clinical management regimen is presented.