The total synthesis of (+/-)-6-oxa-13 beta-ethyl-3-methoxy-8 alpha-gona-1.3.5(10)-trien-17-one and (+/-)-6-oxa-13 beta-ethyl-2-methoxy-8 alpha-gona-1.3.5(10)-trien-17-one was described.
The effect of gonadal hormones on brain tubulin synthesis has been studied in the castrated middle-aged male mouse and testes intact oldaged male mouse.Estrogen exerts potent influences on stimulating tubulin synthesi...The effect of gonadal hormones on brain tubulin synthesis has been studied in the castrated middle-aged male mouse and testes intact oldaged male mouse.Estrogen exerts potent influences on stimulating tubulin synthesis.Treatment with estradiol benzoate or estradiol benzoate and hydroxyprogesterone caproate increase the amount of tubulin by almost 37%-43%.Administration of testosterone propionate can produce a 13%-23% increase.Both estrogen and androgen can stimulate tubulin synthesis after the critical period of brain development but, estrogen plays a stronger role than androgen in stimulating tubulin synthesis in male mouse.展开更多
Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS)...Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).展开更多
Menopause is one of the natural stages of life of women that is associated with instability of vasomotor, flushing, sweating, anxiety and depression, urogenital atrophy and urinary problems. The age range of physiolog...Menopause is one of the natural stages of life of women that is associated with instability of vasomotor, flushing, sweating, anxiety and depression, urogenital atrophy and urinary problems. The age range of physiological event is between 48 - 55 years old. With regard to the role of genetics, nutrition and geographical conditions of the age of menopause in Iranian women is lower than and among 46 - 53 years. With the increase in life expectancy in recent decades, duration of menopause is increased and almost involved a third of the life of women so special issues of this era have had more attention. Since menopause is not the end of the life of a woman and keep her physical and mental health and problems resulting from the process of menopause such as urinary problems and incontinence will lead to improve the quality of life in this period. Many studies have tried to find a therapy for postmenopausal women with stress urinary incontinence using hormone. So this article seeks to examine the effect of conjugated estrogen in stress urinary incontinence of menopausal women with using the library method. The survey showed that by starting menopause, decreasing estrogen causes atrophy of mucosa of urogenital and the lining of the urethra and bladder, estrogen causes to maintain muscle tonicity. Also sacral nerves are also rich in estrogen receptors and by estrogen deficiency, elasticity of the urinary system decreases. Estrogen deficiency causes excitability of nerves and frequency of urine. So estrogen can increase the resistance of the urethra, bladder sensory threshold and sensitivity in Adorno in smooth muscles of the urethra and the rest of detrusor.展开更多
In post-menopausal women,intra-mammary estrogen,which is converted from extra-ovarian estrone(E1),promotes the growth of breast cancer.Since the aromatase inhibitor letrozole does not suppress 17β-estradiol(E2)produc...In post-menopausal women,intra-mammary estrogen,which is converted from extra-ovarian estrone(E1),promotes the growth of breast cancer.Since the aromatase inhibitor letrozole does not suppress 17β-estradiol(E2)production from E1,high intra-mammary E1 concentrations impair letrozole's therapeutic efficacy.Progesterone receptor membrane component 1(Pgrmc1)is a non-classical progesterone receptor associated with breast cancer progression.In the present study,we introduced a Pgrmc1 heterozygous knockout(hetero KO)murine model exhibiting low Pgrmc1 expression,and observed estrogen levels and steroidogenic gene expression.Naïve Pgrmc1 hetero KO mice exhibited low estrogen(E2 and E1)levels and low progesterone receptor(PR)expression,compared to wild-type mice.In contrast,Pgrmc1 hetero KO mice that have been ovariectomized(OVX),including letrozole-treated OVX mice(OVX-letrozole),exhibited high estrogen levels and PR expression.Increased extra-ovarian estrogen production in Pgrmc1 hetero KO mice was observed with the induction of steroid sulfatase(STS).In MCF-7 cell,letrozole suppressed PR expression,but PGRMC1 knockdown increased PR and STS expression.Our presented results highlight the important role of Pgrmc1 in modulating estrogen production when ovary-derived estrogen is limited,thereby suggesting a potential therapeutic approach for letrozole resistance.展开更多
The emerging pandemic of COVID-19 caused by the novel pathogenic human coronavirus SARS-CoV-2 has caused significant morbidity and mortality across the globe,prompting the scientific world to search for preventive mea...The emerging pandemic of COVID-19 caused by the novel pathogenic human coronavirus SARS-CoV-2 has caused significant morbidity and mortality across the globe,prompting the scientific world to search for preventive measures to interrupt the disease process.Demographic data indicates gender-based differences in COVID-19 morbidity with better outcome amongst females.Disparity in sex-dependent morbidity and mortality in COVID-19 patients may be attributed to difference in levels of sex steroid hormones-androgens and estrogens.Evidence suggests that apart from the regulation of viral host factors,immunomodulatory and cardioprotective roles exerted by estrogen and progesterone may provide protection to females against COVID-19.Exploring the underlying mechanisms and beneficial effects of these hormones as an adjuvant to existing therapy may be a step towards improving the outcomes.This article aims to review studies demonstrating the role of sex steroidal hormones in modulating SARS-CoV-2 host factors and summarize plausible biological reasons for sex-based differences seen in COVID-19 mortality.展开更多
There are various well described forms of chronic cholestatic jaundice in adults, such as autoimmune cholangitis, drug-induced cholangitis and intrahepatic cholestasis of pregnancy. We present two cases of prolonged c...There are various well described forms of chronic cholestatic jaundice in adults, such as autoimmune cholangitis, drug-induced cholangitis and intrahepatic cholestasis of pregnancy. We present two cases of prolonged cholestasis following removal of gallstones at endoscopic retrograde cholangiopancreatography （ERCP） and subsequent clear cholangiography. Both patients were taking oral estrogens at the time of presentation, which were subsequently withdrawn. The first case responded rapidly to corticosteroid treatment, and the second case had a much slower resolution with ursodeoxycholic acid. Both cases highlighted the significance of estrogen-induced cholestasis in female patients with protracted jaundice following ERCP and removal of intra-ductal stones. After oral estrogens are discontinued, a short course of steroids needs to be considered.展开更多
AIM: We studied the estrogen receptor (ER) and progesterone receptor (PR) isoforms expression in gastric antrum and corpus of female gerbils and their regulation by estradiol (E2) and progesterone (P4). METHODS: Ovari...AIM: We studied the estrogen receptor (ER) and progesterone receptor (PR) isoforms expression in gastric antrum and corpus of female gerbils and their regulation by estradiol (E2) and progesterone (P4). METHODS: Ovariectomized adult female gerbils were subcutaneously treated with E2, and E2 + P4. Uteri and stomachs were removed, the latter were cut along the greater curvature, and antrum and corpus were excised. Proteins were immunoblotted using antibodies that recognize ER-alpha, ER-beta, and PR-A and PR-B receptor isoforms. Tissues from rats treated in the same way were used as controls. RESULTS: Specific bands were detected for ER-alpha (68 KDa), and PR isoforms (85 and 120 KDa for PR-A and PR-B isoforms, respectively) in uteri, gastric antrum and corpus. We could not detect ER-beta isoform. PR isoforms were not regulated by E2 or P4 in uterus and gastric tissues of gerbils. ER-alpha isoform content was significantly down-regulated by E2 in the corpus, but not affected by hormones in uterus and gastric antrum. CONCLUSION: The presence of ER-alpha and PR isoforms in gerbils stomach suggests that E2 and P4 actions in this organ are in part mediated by their nuclear receptors.展开更多
By means of the enzyme linked affinity histothemical method, 45 cases of squamous cell carcinoma(SCC) of the oral mucosa and 15 cases of the approximately normal oral mucosal tissue were detected for estrogen receptor...By means of the enzyme linked affinity histothemical method, 45 cases of squamous cell carcinoma(SCC) of the oral mucosa and 15 cases of the approximately normal oral mucosal tissue were detected for estrogen receptor(ER) and progesterone receptor(PR). The results indicated that In the SCC tissue of the oral mucosa there were 5 cases of ER+ and PR- and 32 cases of both ER+ and PR+. Thirty-seven cases, the summation of the above two items, were considered as receptor(+),therefore the rate of the receptor(+) being 82.22%. ER+ and PR+ were cd related to the sex and age of patients, the neck lymph nodes' metastasizing or not and affected parts of the tumor, while they were related to the differentiation degree of the tumor. The rate of receptor(+) decreased with the decrease of the differentiation degree of the tumor. By X2 test a remarkable difference between grade Ⅰand grade Ⅲ of SCC of the oral mucosa was shown. It is suggested that SCC of the oral mucosa may probobly be hormone dependent tumor. The authors consider that the SCC detection for ER and PR could not only be one of the indices of biologic characteristics for that tumor but also as bases of anti-hormone treatment.展开更多
文摘The total synthesis of (+/-)-6-oxa-13 beta-ethyl-3-methoxy-8 alpha-gona-1.3.5(10)-trien-17-one and (+/-)-6-oxa-13 beta-ethyl-2-methoxy-8 alpha-gona-1.3.5(10)-trien-17-one was described.
文摘The effect of gonadal hormones on brain tubulin synthesis has been studied in the castrated middle-aged male mouse and testes intact oldaged male mouse.Estrogen exerts potent influences on stimulating tubulin synthesis.Treatment with estradiol benzoate or estradiol benzoate and hydroxyprogesterone caproate increase the amount of tubulin by almost 37%-43%.Administration of testosterone propionate can produce a 13%-23% increase.Both estrogen and androgen can stimulate tubulin synthesis after the critical period of brain development but, estrogen plays a stronger role than androgen in stimulating tubulin synthesis in male mouse.
基金Supported by Research Grants for Nervous and Mental Disorders from the Ministry of Health,Labor and Welfare Health and Labor Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health)+2 种基金Health and Labor Sciences Research Grants,a grant from the Japan Foundation for Neuroscience and Mental Healththe Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (Kunugi H)a Grant-in-Aid for Young Scientists (A) (21680034) from the Ministry of Education,Culture,Sports,Science,and Technology of Japan (Numakawa T)
文摘Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).
文摘Menopause is one of the natural stages of life of women that is associated with instability of vasomotor, flushing, sweating, anxiety and depression, urogenital atrophy and urinary problems. The age range of physiological event is between 48 - 55 years old. With regard to the role of genetics, nutrition and geographical conditions of the age of menopause in Iranian women is lower than and among 46 - 53 years. With the increase in life expectancy in recent decades, duration of menopause is increased and almost involved a third of the life of women so special issues of this era have had more attention. Since menopause is not the end of the life of a woman and keep her physical and mental health and problems resulting from the process of menopause such as urinary problems and incontinence will lead to improve the quality of life in this period. Many studies have tried to find a therapy for postmenopausal women with stress urinary incontinence using hormone. So this article seeks to examine the effect of conjugated estrogen in stress urinary incontinence of menopausal women with using the library method. The survey showed that by starting menopause, decreasing estrogen causes atrophy of mucosa of urogenital and the lining of the urethra and bladder, estrogen causes to maintain muscle tonicity. Also sacral nerves are also rich in estrogen receptors and by estrogen deficiency, elasticity of the urinary system decreases. Estrogen deficiency causes excitability of nerves and frequency of urine. So estrogen can increase the resistance of the urethra, bladder sensory threshold and sensitivity in Adorno in smooth muscles of the urethra and the rest of detrusor.
基金This work was supported by a research fund of Chungnam National University(No.2020-0733-01)This work was supported by Research Scholarship of Chungnam National University.
文摘In post-menopausal women,intra-mammary estrogen,which is converted from extra-ovarian estrone(E1),promotes the growth of breast cancer.Since the aromatase inhibitor letrozole does not suppress 17β-estradiol(E2)production from E1,high intra-mammary E1 concentrations impair letrozole's therapeutic efficacy.Progesterone receptor membrane component 1(Pgrmc1)is a non-classical progesterone receptor associated with breast cancer progression.In the present study,we introduced a Pgrmc1 heterozygous knockout(hetero KO)murine model exhibiting low Pgrmc1 expression,and observed estrogen levels and steroidogenic gene expression.Naïve Pgrmc1 hetero KO mice exhibited low estrogen(E2 and E1)levels and low progesterone receptor(PR)expression,compared to wild-type mice.In contrast,Pgrmc1 hetero KO mice that have been ovariectomized(OVX),including letrozole-treated OVX mice(OVX-letrozole),exhibited high estrogen levels and PR expression.Increased extra-ovarian estrogen production in Pgrmc1 hetero KO mice was observed with the induction of steroid sulfatase(STS).In MCF-7 cell,letrozole suppressed PR expression,but PGRMC1 knockdown increased PR and STS expression.Our presented results highlight the important role of Pgrmc1 in modulating estrogen production when ovary-derived estrogen is limited,thereby suggesting a potential therapeutic approach for letrozole resistance.
基金Jyothi S Prabhu is an awardee of the DBT Wellcome India Alliance clinical and public health intermediate fellowship(Grant no.IA/CPHI/18/1/503938)Anuja Lipsa received post-doctoral fellowship from the above mentioned grant
文摘The emerging pandemic of COVID-19 caused by the novel pathogenic human coronavirus SARS-CoV-2 has caused significant morbidity and mortality across the globe,prompting the scientific world to search for preventive measures to interrupt the disease process.Demographic data indicates gender-based differences in COVID-19 morbidity with better outcome amongst females.Disparity in sex-dependent morbidity and mortality in COVID-19 patients may be attributed to difference in levels of sex steroid hormones-androgens and estrogens.Evidence suggests that apart from the regulation of viral host factors,immunomodulatory and cardioprotective roles exerted by estrogen and progesterone may provide protection to females against COVID-19.Exploring the underlying mechanisms and beneficial effects of these hormones as an adjuvant to existing therapy may be a step towards improving the outcomes.This article aims to review studies demonstrating the role of sex steroidal hormones in modulating SARS-CoV-2 host factors and summarize plausible biological reasons for sex-based differences seen in COVID-19 mortality.
文摘There are various well described forms of chronic cholestatic jaundice in adults, such as autoimmune cholangitis, drug-induced cholangitis and intrahepatic cholestasis of pregnancy. We present two cases of prolonged cholestasis following removal of gallstones at endoscopic retrograde cholangiopancreatography （ERCP） and subsequent clear cholangiography. Both patients were taking oral estrogens at the time of presentation, which were subsequently withdrawn. The first case responded rapidly to corticosteroid treatment, and the second case had a much slower resolution with ursodeoxycholic acid. Both cases highlighted the significance of estrogen-induced cholestasis in female patients with protracted jaundice following ERCP and removal of intra-ductal stones. After oral estrogens are discontinued, a short course of steroids needs to be considered.
文摘AIM: We studied the estrogen receptor (ER) and progesterone receptor (PR) isoforms expression in gastric antrum and corpus of female gerbils and their regulation by estradiol (E2) and progesterone (P4). METHODS: Ovariectomized adult female gerbils were subcutaneously treated with E2, and E2 + P4. Uteri and stomachs were removed, the latter were cut along the greater curvature, and antrum and corpus were excised. Proteins were immunoblotted using antibodies that recognize ER-alpha, ER-beta, and PR-A and PR-B receptor isoforms. Tissues from rats treated in the same way were used as controls. RESULTS: Specific bands were detected for ER-alpha (68 KDa), and PR isoforms (85 and 120 KDa for PR-A and PR-B isoforms, respectively) in uteri, gastric antrum and corpus. We could not detect ER-beta isoform. PR isoforms were not regulated by E2 or P4 in uterus and gastric tissues of gerbils. ER-alpha isoform content was significantly down-regulated by E2 in the corpus, but not affected by hormones in uterus and gastric antrum. CONCLUSION: The presence of ER-alpha and PR isoforms in gerbils stomach suggests that E2 and P4 actions in this organ are in part mediated by their nuclear receptors.
文摘By means of the enzyme linked affinity histothemical method, 45 cases of squamous cell carcinoma(SCC) of the oral mucosa and 15 cases of the approximately normal oral mucosal tissue were detected for estrogen receptor(ER) and progesterone receptor(PR). The results indicated that In the SCC tissue of the oral mucosa there were 5 cases of ER+ and PR- and 32 cases of both ER+ and PR+. Thirty-seven cases, the summation of the above two items, were considered as receptor(+),therefore the rate of the receptor(+) being 82.22%. ER+ and PR+ were cd related to the sex and age of patients, the neck lymph nodes' metastasizing or not and affected parts of the tumor, while they were related to the differentiation degree of the tumor. The rate of receptor(+) decreased with the decrease of the differentiation degree of the tumor. By X2 test a remarkable difference between grade Ⅰand grade Ⅲ of SCC of the oral mucosa was shown. It is suggested that SCC of the oral mucosa may probobly be hormone dependent tumor. The authors consider that the SCC detection for ER and PR could not only be one of the indices of biologic characteristics for that tumor but also as bases of anti-hormone treatment.
