RESUMO
The relationship between menopause and the development of metabolic diseases is well established. In postmenopause women, there is an expansion of visceral white adipose tissue (WATv), which highly contributes to the rise of circulating lipids. Meanwhile, muscle glucose uptake decreases and hepatic glucose production increases. Consequently, in the pancreas, lipotoxicity and glycotoxicity lead to deficient insulin production. These factors initiate an energy imbalance and enhance the probability of developing cardiovascular and metabolic diseases. Although the activation of estradiol receptors (ER) has been shown to be beneficial for the WAT stock pattern, leading to the insulin-sensitive phenotype, authors have described the risk of these receptors' activation, contributing to neoplasia development. The selective activation of beta-type ER (ERß) seems to be a promising strategy in the treatment of energy imbalance, acting on several tissues of metabolic importance and allowing an intervention with less risk for the development of estrogen-dependent neoplasia. However, the literature on the risks and benefits of selective ERß activation still needs to increase. In this review, several aspects related to ERß were considered, such as its physiological role in tissues of energy importance, beneficial effects, and risks of its stimulation during menopause. PubMed, SciELO, Cochrane, and Medline/Bireme databases were used in this study.
Assuntos
Biomarcadores , Pós-Menopausa/metabolismo , Receptores de Estradiol/metabolismo , Tecido Adiposo/metabolismo , Suscetibilidade a Doenças , Estrogênios/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/metabolismo , Especificidade de Órgãos , Receptores de Estradiol/genética , Receptores de Estrogênio/metabolismo , Transdução de SinaisRESUMO
Biotin deficiency and biotin excess have both been found to affect reproduction and cause teratogenic effects. In the reproductive tract, however, the effects of biotin have not been well established yet. We investigated the effects of varying biotin content diets on the oestrus cycle, ovarian morphology, estradiol and progesterone serum levels, and the uterine mRNA abundance of their nuclear receptors, as well as on the activity of the estradiol-degrading group of enzymes cytochrome P450 (CYP) in the liver. Three-week-old female BALB/cAnN Hsd mice were fed a biotin-deficient, a biotin-control, or a biotin-supplemented diet (0, 7.2 or 400 micromol of free biotin/kg diet, respectively) over a period of nine weeks. Striking effects were observed in the biotin-deficient group: mice showed arrested estrous cycle on the day of diestrus and changes in ovary morphology. Estradiol serum concentration increased 49.2% in biotin-deficient mice compared to the control group, while the enzymatic activities of CYP1A2 and CYP2B2 increased (P<0.05). The mRNA abundance of nuclear estrogen and progesterone receptors decreased in the biotin-deficient mice. In the biotin-supplemented group we found that, in spite of a significant (P<0.05) decrease in the number of primary and Graafian follicles and in CYP1A2 activities, mice exhibited 105.4% higher serum estradiol concentration than the control group. No changes in the expression of the nuclear receptors were observed. No significant differences were observed in serum progesterone among the groups. Our results indicate that both the deficiency and the excess of biotin have significant effects on the female mouse reproductive system.
Assuntos
Biotina/deficiência , Biotina/farmacologia , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Animais , Biotina/administração & dosagem , Biotina/sangue , Peso Corporal/efeitos dos fármacos , Dieta , Estradiol/sangue , Ciclo Estral/efeitos dos fármacos , Feminino , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos BALB C , Tamanho do Órgão/efeitos dos fármacos , Ovário/anatomia & histologia , Ovário/efeitos dos fármacos , Progesterona/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Estradiol/genética , Receptores de Progesterona/genética , Útero/efeitos dos fármacos , Útero/metabolismoRESUMO
The objective of this comparative study was to determine the influence of changes in estradiol and progesterone during ovulatory vs. anovulatory cycles on levels of estradiol receptor (ER) and progesterone receptor (PgR) in endometrium. Thirty women (range age 20-35 years) were divided into three groups: women with a history of habitual abortion, obese women with menstrual disorders, and women with regular ovulatory cycles as well as proven fertility. A single venous blood sample and an endometrial sample were simultaneously obtained during the secretory phase of the menstrual cycle, in order to measure estradiol and progesterone levels and ER and PgR concentrations in cytosol and salt-extracted nucleosol. Plasma estradiol levels were not different between groups. Plasma progesterone was two times higher in fertile women than in habitual aborters. In endometrial tissue, progesterone content was 200 times higher in fertile women than in habitual aborters. ER and PgR were lower in the cytosol than in the nuclear fraction in fertile and obese women. Both receptors were at their lowest level in the cytosol and nuclear compartment of women with recurrent miscarriage. Fluctuations mainly in the sex hormone progesterone, in plasma and endometrium tissue, could interfere with ER and PgR levels.