Effects of post-ovariectomy time frame and age on the antidepressant-like actions of estradiol and prolame in female rats.

Estrogen replacement therapy (ERT) is an effective treatment for symptoms associated with climacteric and depression some women experience during perimenopause and menopause. The antidepressant-like effects of ERT may depend on the type of estrogen, age, and time when restitution is initiated after hormonal decline. Prolame is a synthetic steroid with estrogenic and antidepressant-like effects that may produce fewer adverse effects. We hypothesize that such actions of prolame on females depend on age and the duration of hormone deprivation period. We assessed the antidepressant-like effects of 17ß-estradiol (E2) and prolame in young and middle-aged rats across different post-ovariectomy (Ovx) time frames. Independent groups of young adults and middle-aged female rats were tested in the forced swimming test (FST) at 3, 8, 16, and 24 weeks post-Ovx. Prolame and E2 were administered in a sub-chronic schedule consisting of three injections before the FST. Likewise, the utero-trophic effects of these hormones were analyzed. We found that E2 and prolame reduced immobility in young rats 3 and 8 weeks after Ovx; in contrast, only prolame produced this effect in middle-aged rats three weeks post-Ovx. E2 and prolame increased the animals' utero-somatic index at all post-Ovx times, but the action of E2 and prolame produced a greater response in young adult rats. Our findings showed that the antidepressant-like effects of E2 and prolame depend on the post-Ovx time frame, age, and estrogen type. Interestingly, our results indicate that, in contrast to E2, prolame maintained its antidepressant effect in middle-aged rats.

Antidepressant-like effects of acupuncture via modulation of corticosterone, sex hormones, and hippocampal BDNF expression in male rats.

BACKGROUND: Post-weaning social isolated rodents exhibit pathophysiological changes associated with depression including adrenal axis hyperactivity, gonadal hormone level disturbances, molecular alterations in hippocampus, and immobility behavior in the forced swimming test (FST). Although acupuncture by absorbable thread implantation (acu-catgut, AC) elicits antidepressant-like effects in social isolated rats, AC effects on neuroendocrine and hippocampal molecular alterations have been less characterized. OBJECTIVE: To investigate the participation of gonadal hormones, corticosterone, and brain-derived neurotrophic factor (BDNF) hippocampal expression, on the AC antidepressant-like effects in social isolated male rats. METHODS: Sprague-Dawley male rats were raised in social isolation (SI) or standard conditions, for 11 weeks. AC (on Baihui (Du20), Yintang (E X-HN3), Shenshu (BL 23), Pishu (BL 20), Ganshu (BL 18), Xinshu (BL 15) and Guanyuan (Ren 4)), or Sham-AC (puncturing of acupoints without embedding the thread), was applied during the last three weeks of isolation period. Rats were evaluated in the FST; hormones plasmatic levels and hippocampal BDNF content were quantified by ELISA and Western blotting, respectively. RESULTS: Social isolated rats showed more immobility in the FST and had lower testosterone and estradiol levels, higher corticosterone levels, and reduced hippocampal BDNF content than controls. BDNF level in hippocampus inversely correlated to depression-like behavior. AC but not sham-AC normalized immobility behavior, steroid hormone levels, and BDNF content, as in rats raised in a social environment. CONCLUSIONS: AC antidepressant effect could be related to an improvement of hippocampal BDNF protein expression, as well as corticosterone and sex hormones disturbances associated with prolonged exposure to stress caused by social isolation. Present findings have implications for depression treatment in individuals early exposed to stress.

Influence of the type of childhood violence on cannabis abuse and dependence among adolescents: a systematic review and meta-analysis. / Tipos de violencia en la infancia que inciden en el abuso y dependencia de cannabis entre adolescentes: una revisión sistemática y metaanálisis.

The use of cannabis for recreational purposes has increased worldwide, and the proportion of cannabis users in the adolescent population is high. Susceptibility to cannabis use involves various factors, including childhood adversity; however, the effects of different types of violence on cannabis use have not been evaluated. The aim of this review was to analyze the effects of different types of violence on cannabis use in adolescence. We searched electronic databases (PubMed, Science Direct, Web of Science, Ovid and CONRICyT) using the following algorithm: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considering all articles published up to November 3th, 2017. Odds ratios (ORs) were calculated for the effects of experiencing different types of violence during childhood on cannabis use. Six studies, which represented 10 843 adolescents of both sexes, were ultimately included in the systematic review and meta-analysis. Three types of early-life adversity were associated with cannabis abuse/dependence: physical abuse (OR: 1.58, 95% CI [1.01-2.46]), sexual abuse (OR: 2.35, 95% CI [1.64-3.35]), and witnessing violence (OR: 3.22, 95% CI [0.63-16.54]). The results indicated that two specific types of child maltreatment, sexual and physical abuse, were critical factors affecting vulnerability to cannabis use in adolescence. The number of studies examining other types of violence was limited. The results highlighted the importance of enhancing efforts to prevent violence, particularly sexual abuse, as part of integral programs designed to prevent cannabis abuse and dependence.

El uso recreativo de cannabis ha incrementado en todo el mundo, principalmente en la población adolescente. Se ha propuesto que la adversidad en la infancia contribuye al consumo de esta droga. El objetivo de esta revisión sistemática y metaanálisis fue analizar el efecto de diferentes tipos de violencia en la infancia sobre el consumo de cannabis en la adolescencia. Se realizó una búsqueda en diferentes bases de datos (PubMed, Science Direct, Web of Science, Ovid y CONRICyT) usando los términos de búsqueda: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considerando todos los artículos publicados hasta el 3 de noviembre de 2017. Se calcularon los Odds Ratio (OR) del consumo de cannabis en adolescentes, para los diferentes tipos de abuso infantil, así como sus intervalos de confianza del 95% (IC 95%). Se identificaron seis estudios, que incluyeron 10 843 adolescentes de uno u otro sexo. La asociación entre la violencia y el abuso/dependencia de cannabis en la adolescencia mostró los siguientes valores: abuso físico (OR: 1,58, IC 95% [1,01­2,46]), abuso sexual (OR: 2,35, IC 95% [1,64­3,35]), y ser testigo de violencia (OR: 3,22, IC 95% [0,63­16,54]). Los resultados muestran que el abuso sexual o físico durante etapas tempranas de la vida aumenta el riesgo de consumo de cannabis en la adolescencia. Los estudios que evaluaron otras formas de violencia fueron escasos. Los resultados destacan la importancia de diseñar programas integrales para reducir el uso y dependencia de cannabis mediante estrategias enfocadas a la prevención de la violencia en la infancia.

Tipos de violencia en la infancia que inciden en el abuso y dependencia de cannabis entre adolescentes: una revisión sistemática y metaanálisis / Influence of the type of childhood violence on cannabis abuse and dependence among adolescents: a systematic review and meta-analysis

El uso recreativo de cannabis ha incrementado en todo el mundo, principalmente en la población adolescente. Se ha propuesto que la adversidad en la infancia contribuye al consumo de esta droga. El objetivo de esta revisión sistemática y metaanálisis fue analizar el efecto de diferentes tipos de violencia en la infancia sobre el consumo de cannabis en la adolescencia. Se realizó una búsqueda en diferentes bases de datos (PubMed, Science Direct, Web of Science, Ovid y CONRICyT) usando los términos de búsqueda: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considerando todos los artículos publicados hasta el 3 de noviembre de 2017. Se calcularon los Odds Ratio (OR) del consumo de cannabis en adolescentes, para los diferentes tipos de abuso infantil, así como sus intervalos de confianza del 95% (IC 95%). Se identificaron seis estudios, que incluyeron 10 843 adolescentes de uno u otro sexo. La asociación entre la violencia y el abuso/dependencia de cannabis en la adolescencia mostró los siguientes valores: abuso físico (OR: 1,58, IC 95% [1,01-2,46]), abuso sexual (OR: 2,35, IC 95% [1,64-3,35]), y ser testigo de violencia (OR: 3,22, IC 95% [0,63-16,54]). Los resultados muestran que el abuso sexual o físico durante etapas tempranas de la vida aumenta el riesgo de consumo de cannabis en la adolescencia. Los estudios que evaluaron otras formas de violencia fueron escasos. Los resultados destacan la importancia de diseñar programas integrales para reducir el uso y dependencia de cannabis mediante estrategias enfocadas a la prevención de la violencia en la infancia

The use of cannabis for recreational purposes has increased worldwide, and the proportion of cannabis users in the adolescent population is high. Susceptibility to cannabis use involves various factors, including childhood adversity; however, the effects of different types of violence on cannabis use have not been evaluated. The aim of this review was to analyze the effects of different types of violence on cannabis use in adolescence. We searched electronic databases (PubMed, Science Direct, Web of Science, Ovid and CONRICyT) using the following algorithm: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considering all articles published up to November 3th, 2017. Odds ratios (ORs) were calculated for the effects of experiencing different types of violence during childhood on cannabis use. Six studies, which represented 10 843 adolescents of both sexes, were ultimately included in the systematic review and meta-analysis. Three types of early-life adversity were associated with cannabis abuse/dependence: physical abuse (OR: 1.58, 95% CI [1.01-2.46]), sexual abuse (OR: 2.35, 95% CI [1.64-3.35]), and witnessing violence (OR: 3.22, 95% CI [0.63-16.54]). The results indicated that two specific types of child maltreatment, sexual and physical abuse, were critical factors affecting vulnerability to cannabis use in adolescence. The number of studies examining other types of violence was limited. The results highlighted the importance of enhancing efforts to prevent violence, particularly sexual abuse, as part of integral programs designed to prevent cannabis abuse and dependence

Role of Estradiol in the Expression of Genes Involved in Serotonin Neurotransmission: Implications for Female Depression.

BACKGROUND: In women, changes in estrogen levels may increase the incidence and/or symptomatology of depression and affect the response to antidepressant treatments. Estrogen therapy in females may provide some mood benefits as a single treatment or might augment clinical response to antidepressants that inhibit serotonin reuptake. OBJECTIVE: We analyzed the mechanisms of estradiol action involved in the regulation of gene expression that modulates serotonin neurotransmission implicated in depression. METHOD: Publications were identified by a literature search on PubMed. RESULTS: The participation of estradiol in depression may include regulation of the expression of tryptophan hydroxylase-2, monoamine oxidase A and B, serotonin transporter and serotonin-1A receptor. This effect is mediated by estradiol binding to intracellular estrogen receptor that interacts with estrogen response elements in the promoter sequences of tryptophan hydroxylase-2, serotonin transporter and monoamine oxidase-B. In addition to directly binding deoxyribonucleic acid, estrogen receptor can tether to other transcription factors, including activator protein 1, specificity protein 1, CCAAT/enhancer binding protein ß and nuclear factor kappa B to regulate gene promoters that lack estrogen response elements, such as monoamine oxidase-A and serotonin 1A receptor. CONCLUSION: Estradiol increases tryptophan hydroxylase-2 and serotonin transporter expression and decreases the expression of serotonin 1A receptor and monoamine oxidase A and B through the interaction with its intracellular receptors. The understanding of molecular mechanisms of estradiol regulation on the protein expression that modulates serotonin neurotransmission will be helpful for the development of new and more effective treatment for women with depression.

Corrigendum to "Young-Adult Male Rats' Vulnerability to Chronic Mild Stress Is Reflected by Anxious-Like instead of Depressive-Like Behaviors".

[This corrects the article DOI: 10.1155/2016/5317242.].

Regulation of gene expression by progesterone in cancer cells: effects on cyclin D1, EGFR and VEGF.

Progesterone (P4) participates in the regulation of several physiological and pathological processes in mammals through the interaction with its intracellular receptors (PR), which are ligand-dependent transcription factors.Many human cancers depend on P4 for growth and metastasis, especially cancers of reproductive tissues. In women,administration of combined estrogen and progestin hormone replacement therapy for postmenopausal symptoms increases the risk of breast cancer relative to women taking estrogens alone. P4 exerts its actions through various mechanisms classified as classical and non-classical. PR has dual functions as a nuclear transcription factor and as a modulator of cell signaling pathways. Many PR target genes do not contain canonical progesterone response elements (PRE) in their promoter regions and may thus be regulated by PR tethering to other transcription factors and/or rapid signaling,independent of direct PR DNA binding. We review the mechanisms involved in P4 effects on genes implicated in control of cell cycle, proliferation, angiogenesis and metastasis, such as cyclin D1 and epidermal growth factor receptor (EGFR)whose promoters lack PRE sequences, and vascular endothelial growth factor (VEGF) which gene contains PRE in its promoter region. The understanding of the molecular mechanisms involved in the regulation of cyclin D1, EGFR and VEGF expression by P4 will be helpful for the development of new cancer therapies.

Progesterone receptor and SRC-1 participate in the regulation of VEGF, EGFR and Cyclin D1 expression in human astrocytoma cell lines.

Astrocytomas are the most common primary brain tumors in humans. It has been reported that vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), cyclin D1 and progesterone receptor (PR) expression levels are elevated in patients with high-grade astrocytomas. Progesterone (P) regulates astrocytomas growth through its interaction with PR, which recruits coregulatory proteins such as steroid receptor coactivator-1 (SRC-1) that are required for efficient transcriptional activation. The regulation of VEGF, EGFR and cyclin D1 expression by P in human astrocytoma cells is not known. We studied the role of PR and SRC-1 in the expression of VEGF, EGFR and cyclin D1 mediated by P in human astrocytoma cell lines grade III (U373) and IV (D54). P significantly increased VEGF and EGFR mRNA expression after 12h of treatment in D54 cells that was reflected at protein level 24h after treatment. This effect was blocked by the PR antagonist, RU 486. In U373 cells cyclin D1 mRNA and protein expression was induced by P after 6 and 8h of treatment, respectively, and this effect was blocked with RU 486. Transfection with short hairpin RNA targeting coactivator SRC-1 significantly reduced VEGF expression after 24h of treatment. Collectively, our results indicate that P regulates VEGF and EGFR expression in D54 cells and cyclin D1 expression in U373 through PR, and that SRC-1 participates in the regulation of VEGF expression.

Estradiol increases cell growth in human astrocytoma cell lines through ERα activation and its interaction with SRC-1 and SRC-3 coactivators.

Estradiol (E2) regulates several cellular functions through the interaction with estrogen receptor subtypes, ERα and ERß, which present different functional and regulation properties. ER subtypes have been identified in human astrocytomas, the most common and aggressive primary brain tumors. We studied the role of ER subtypes in cell growth of two human astrocytoma cell lines derived from tumors of different evolution grades: U373 and D54 (grades III and IV, respectively). E2 significantly increased the number of cells in both lines and the co-administration with an ER antagonist (ICI 182, 780) significantly blocked E2 effects. ERα was the predominant subtype in both cell lines. E2 and ICI 182, 780 down-regulated ERα expression. The number of U373 and D54 cells significantly increased after PPT (ERα agonist) treatment but not after DPN (ERß agonist) one. To determine the role of SRC-1 and SRC-3 coactivators in ERα induced cell growth, we silenced them with RNA interference. Coactivator silencing blocked the increase in cell number induced by PPT. The content of proteins involved in proliferation and metastasis was also determined after PPT treatment. Western blot analysis showed that in U373 cells the content of PR isoforms (PR-A and PR-B), EGFR, VEGF and cyclin D1 increased after PPT treatment while in D54 cells only the content of EGFR was increased. Our results demonstrate that E2 induces cell growth of human astrocytoma cell lines through ERα and its interaction with SRC-1 and SRC-3 and also suggest differential roles of ERα on cell growth depending on astrocytoma grade.

Role of progesterone in human astrocytomas growth.

Progesterone (P) participates in the regulation of several reproductive processes such as ovulation and sexual behavior, however, this hormone also participates in non-reproductive processes, such as neural excitability, learning and memory, and pathological processes such as cancer. P mainly elicits its effects by interaction with its intracellular receptor (PR), which is a ligand-activated transcription factor that modifies the expression of genes involved in the control of cell growth and proliferation, such as vascular endothelial growth factor and epidermal growth factor receptor. Two PR isoforms have been reported: PR-B and PR-A, which present different function and regulation. PR isoforms are expressed in U373 and D54 cell lines, which are derived from grades III and IV of human astrocytomas, respectively. In both cells lines P increases the number of astrocytomas cells. The PR antagonist, RU486, blocked P effects and its treatment alone significantly reduced human astrocytomas cell growth in vitro. The over-expression of PR-A in U373 cells significantly reduced P effects. These data suggest that P regulates human astrocytomas cell proliferation through the interaction with PR.

Progesterone and estradiol effects on SRC-1 and SRC-3 expression in human astrocytoma cell lines.

Progesterone (P(4)) and estradiol (E(2)) regulate many cell functions through their interaction with specific intracellular receptors, which require the participation of coactivators such as SRC-1 and SRC-3 for enhancing their transcriptional activity. Coactivator expression is altered in many cancers and in some of them their expression is regulated by P(4) and E(2). In this study, we determined progesterone and estrogen receptor isoform expression in two human astrocytoma cell lines with different evolution grade (U373, grade III; and D54, grade IV) by Western Blot. We studied the role of P(4) and E(2) on SRC-1 and SRC-3 expression in U373 and D54 cell lines by RT-PCR and Western blot. In U373 cells, P(4) did not modify SRC-1 expression, but in D54 cells it increased SRC-1 mRNA expression after 12 h of treatment without significant changes after 24 h. P(4) also increased SRC-1 protein content after 24 h, but reduced it after 48 h. E(2) did not change SRC-1 expression in any cell line. SRC-3 expression was not regulated by either E(2) or P(4). Our data suggest that SRC-1 and SRC-3 expression is differentially regulated by sex steroid hormones in astrocytomas and that P(4) regulates SRC-1 expression depending on the evolution grade of human astrocytoma cells.

Progesterone induces scolex evagination of the human parasite Taenia solium: evolutionary implications to the host-parasite relationship.

Taenia solium cysticercosis is a health problem in underdeveloped and developed countries. Sex hormones are involved in cysticercosis prevalence in female and male pigs. Here, we evaluated the effects of progesterone and its antagonist RU486 on scolex evagination, which is the initial step in the development of the adult worm. Interestingly, progesterone increased T. solium scolex evagination and worm growth, in a concentration-independent pattern. Progesterone effects could be mediated by a novel T. solium progesterone receptor (TsPR), since RU486 inhibits both scolex evagination and worm development induced by progesterone. Using RT-PCR and western blot, sequences related to progesterone receptor were detected in the parasite. A phylogenetic analysis reveals that TsPR is highly related to fish and amphibian progesterone receptors, whereas it has a distant relation with birds and mammals. Conclusively, progesterone directly acts upon T. solium cysticerci, possibly through its binding to a progesterone receptor synthesized by the parasite.