Papel de los estrógenos en el sistema nervioso central y su implicancia en los trastornos psiquiátricos: segunda parte / Role of estrogens in the central nervous system and their Implication for psychiatric disorders: second part

En esta segunda parte del trabajo se focaliza en cómo los estrógenos, con sus diferentes concentraciones a lo largo de las distintas etapas de la vida, por su presencia o ausencia, vulnerabilizan a padecer determinadas patologías neuropsiquiátricas, así como también protegen de algunas otras. En este sentido, se considera que la patología de la mujer debería incluir profundos conocimientos sobre la implicancia que las hormonas sexuales tienen en el desarrollo de determinadas enfermedades neuropsiquiátricas. Se relevan también otros estudios sobre la administración de terapia hormonal de reemplazo, ya que son los procesos neurodegenerativos, como la enfermedad de Alzheimer, los que mayor lugar han tenido entre las investigaciones de las últimas décadas. Allí los resultados se vislumbran promisorios, pues la administración de estrógenos inmediatamente después de la menopausia revela tener efecto en la prevención del desarrollo de estos procesos, lo que no ocurre una vez iniciados los procesos neurodegenerativos. Se incluyen, a su vez, otros trabajos en otras patologías psiquiátricas, en donde se ha evaluado la eficacia de la prescripción de estrógenos, como ser en determinadas formas de depresión mayor (como coadyuvante), con buenos resultados. A pesar de los avances en el campo de la neurociencia y la influencia que ésta ha tenido en el conocimiento de las enfermedades psiquiátricas, es necesario proseguir con las investigaciones en donde se incluyan nuevos fármacos, como ser hormonas sexuales y SERMs, que seguramente traerán aportes promisorios en determinadas patologías neuropsiquiátricas.

The second part of the article focuses on estrogens, with their varying concentrations, throughout the different stages of life, which, whether by their presence or absence, predispose to suffering from certain neuropsychiatric diseases, just as they protect the individual from some others. In this sense, it is considered that female pathology should involve a deep knowledge on the impact that sexual hormones have on the development of certain neuropsychiatric diseases. The article also includes other studies on the administration of hormone replacement therapy, since it is neurodegenerative processes, such as Alzheimer's Disease, which occupied a leading place in investigations during the past decades. In such investigations, outcomes seem to be promising, since the administration of estrogens right after menopause demonstrates to have an impact on preventing the development of these processes, which does not occur once neurodegenerative processes have started. Also included are other investigations conducted on other psychiatric pathologies, in which the efficacy of prescribing estrogens, such as for certain forms of major depression (as adjunctive therapy) are evaluated, with positive results. Despite the advances in neuroscience and its influence on the knowledge of psychiatric diseases, it is necessary to continue preforming investigations that include new pharmacological drugs, such as sexual hormones and SERMs, which will possibly bring about promissory contributions to certain neuropsychiatric diseases.

Estrogen modulates bone marrow-derived DCs in SLE murine model-(NZB x NZW) F1 female mice.

Dendritic cells (DCs) in the patient and animal models of systemic lupus erythematosus (SLE) are abnormal, but the detailed mechanism is unclear. Estrogen can modulate DCs in biological condition and estrogen concentration is related to the onset and development of SLE. So the control of estrogen on DCs might lead to the disorder of DCs. To prove the hypothesis, we detected the effects of 17beta-estradiol (E2) on bone marrow (BM)-derived DCs in SLE murine model-(NZB x NZW) F1 (NZB/w F1) female mice before and after the disease onset. We found that E2 mainly enhanced the expression of surface molecule CD40, MHCII and the stimulation activity of immature DCs, but weakened the activity of mature DCs. E2 decreased the production of cytokines IL-6, IL-10, IL-12 and TNFalpha of DCs in young mice, but increased them in old mice. Tamoxifen could antagonize the E2 effect. E2 changed the expression of estrogen receptor-alpha (ER alpha) in DCs. The level of ER alpha in DCs of various old mice and the differentiation states varied. The results suggest that E2 can modulate the functions of BM-derived DCs in SLE pathology. The modulation is achieved by binding ER. The effects of E2 on DCs are different depending on the progression of SLE and cell differentiation status. This might be due to the difference of ER expression.

Estradiol regulates monocyte chemotactic protein-1 in human coronary artery smooth muscle cells: a mechanism for its antiatherogenic effect.

OBJECTIVE: The protective effect of estrogen against early atherosclerosis in animal models is well documented, but the mechanisms responsible for this effect are not well understood. The earliest recognizable event in the pathogenesis of atherosclerosis is an increased recruitment of macrophages into the arterial subendothelium. Macrophages first play a protective role by removing low-density lipoproteins, but when the cholesterol is in excess, macrophages are converted into foam cells and form atheromas. Recent human and animal data indicate that the recruitment of macrophages to the arterial wall is mediated by monocyte chemotactic protein-1 (MCP-1). We hypothesized that one of the mechanisms of estrogen's protective effect against atherosclerosis may be the down-regulation of MCP-1 expression in the arterial wall. DESIGN: Human coronary artery smooth muscle cells were replicated to confluence in smooth muscle cell basal medium supplemented with growth factors and 5% fetal bovine serum. Before each experiment, cells were incubated for 24 h with phenol red-free medium containing 5% charcoal-stripped calf serum, and then they were treated with various concentrations of 17beta-estradiol as well as selective estrogen receptor (ER) modulators, raloxifene and tamoxifen. MCP-1 messenger ribonucleic acid (mRNA) levels were quantified by Northern blots. MCP-1 protein was quantified using an enzyme-linked immunosorbent assay. ER expression was evaluated by reverse transcriptase-polymerase chain reaction. RESULTS: Human coronary artery smooth muscle cells expressed MCP-1 mRNA and produced MCP-1 protein. Estradiol induced up to 40% inhibition in mRNA expression at concentrations 10-9 M and higher. Raloxifene and tamoxifen also resulted in an inhibition, but the inhibition was less than when induced by estradiol. Estradiol also inhibited the MCP-1 protein production in a concentration-dependent manner (p < 0.05). Coronary smooth muscle cells expressed both ERalpha and ERbeta. CONCLUSION: Our findings suggest that one of the mechanisms by which estrogen prevents atherosclerosis is by down-regulating MCP-1 expression, thus decreasing macrophage recruitment to the arterial wall.