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1.
PLoS One ; 15(9): e0239218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32931507

RESUMO

Endocrine profiling is an increasingly utilized tool for detecting pregnancies in wild populations of mammals. Given the difficulty in calculating reproductive rates of Pacific walruses (Odobenus rosmarus divergens) the use of endocrine techniques for determining pregnancy rates could be particularly useful for management of the population. The goals of this study were to 1) determine if progesterone and total estrogen concentrations in ovarian tissues of female walruses could be used to determine reproductive state and 2) determine if walruses undergo a functional postpartum estrus, as is seen in other pinnipeds. Ovaries were collected from female walruses (n = 13) hunted in subsistence hunts by Alaska Native communities. Females were categorized as postpartum, full-term pregnant, pregnant diapause or unbred. Total estrogen concentrations were greatest in unbred (n = 2) and pregnant (n = 2) females. Progesterone concentrations were also nominally larger in unbred (n = 2) than pregnant (n = 2) and postpartum (n = 9) animals. Small samples sizes precluded the use of statistical comparisons among groups. Corpora lutea tissue samples in this study did not reflect the presence of a postpartum estrus in the month of May as postpartum females yielded lower total estrogen concentrations than unbred or pregnant animals. Both unbred animals were in a state of pseudopregnancy, which has not been physiologically described for this species before. The progesterone profiles in late (59 ng/g) and early (140 ng/g) pregnancy were lower than expected and fell within the range of the postpartum females (36-210 ng/g), suggesting low production of the hormone by the corpus luteum during these phases of pregnancy. Profiling reproductive hormones in free-ranging walruses demonstrates that an endocrine approach may be a valuable tool for determining reproductive status of females, however increased sample sizes and time of year must be considered to accurately separate pregnant versus pseudopregnant individuals.


Assuntos
Estrogênios/fisiologia , Progesterona/fisiologia , Pseudogravidez/veterinária , Morsas/fisiologia , Animais , Biomarcadores , Feminino
2.
PLoS One ; 15(8): e0237032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790683

RESUMO

The behavioral activation system (BAS) and the behavioral inhibition system (BIS) have been proposed to relate to stable traits that predict inter-individual differences in motivation. Prior reports point dopamine (DA) pathways, mainly including ventral tegmental area (VTA) and substantia nigra (SN), implicate in subserving reward-related functions associated with BAS and inhibitory functions related with BIS. However, as an important factor that affects DA releasing, it remains an open question whether the ovarian hormones may also be related to BIS/BAS. Here, to investigate effects of the estradiol (E2) and progesterone (PROG) on BIS/BAS and related DA pathways, we employed a BIS/BAS scale and the resting-state functional magnetic resonance imaging (fMRI) during the late follicular phase (FP) and the mid-luteal phase (LP). On the behavioral level, when women had high PROG levels, their E2 levels were found positively correlated with BIS scores, but those women whose PROG levels were low, their E2 levels were negative correlation with BIS scores. On the neural level, we demonstrated BAS was related with the VTA pathway, included brain reward regions of nucleus accumbens (NAc) and orbitofrontal cortex (OFC). Meanwhile, the BIS was correlated with the SN-dorsolateral prefrontal cortex (dlPFC) pathway. ROI-based resting-state functional connectivity (RSFC) analyses further revealed that, RSFC between the SN and dlPFC was modulated by ovarian hormones. With higher PROG levels, increased E2 levels among women were accompanied by stronger RSFC of the SN-dlPFC, but when PROG levels were low, E2 levels were negatively correlated with the SN-dlPFC RSFC. These findings revealed a combined enhancement effect of E2 and PROG on BIS, and the SN-dlPFC pathway was mainly involved in this process.


Assuntos
Encéfalo/fisiologia , Dopamina/fisiologia , Inibição Psicológica , Motivação/fisiologia , Ovário/fisiologia , Adulto , Afeto/fisiologia , Encéfalo/diagnóstico por imagem , Neurônios Dopaminérgicos/fisiologia , Estradiol/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Progesterona/fisiologia , Psicofisiologia , Substância Negra/diagnóstico por imagem , Substância Negra/fisiologia , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/fisiologia , Adulto Jovem
3.
Sheng Li Xue Bao ; 72(1): 105-114, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32099988

RESUMO

Embryo implantation is crucial for the establishment and maintenance of successful pregnancy and requires the synchronization between implantation-competent blastocyst and receptive uterus. In assisted reproductive technologies, recognition of uterine receptivity is the limiting factor for improving pregnancy rate. It has been previously reported that embryo implantation involves the activation and inactivation of numerous signaling molecules which may influence the proliferation and differentiation of uterine epithelial cells, epithelial polarity, luminal closure, embryo orientation, epithelial-stromal interactions, gland development, etc. Here we summarize the function of estrogen, progesterone, leukemia inhibitory factor (LIF), microRNA (miRNA), channel protein and signaling pathways in embryo implantation and explore their regulatory network to provide theoretical basis for the treatment of infertility and development of safe and efficient contraceptives.


Assuntos
Implantação do Embrião , Útero/fisiologia , Blastocisto/fisiologia , Estrogênios/fisiologia , Feminino , Humanos , Fator Inibidor de Leucemia/fisiologia , MicroRNAs/genética , Gravidez , Progesterona/fisiologia , Transdução de Sinais
4.
Dev Biol ; 458(1): 43-51, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610144

RESUMO

The steroid hormones are instrumental for the growth of mammary epithelial cells. Our previous study indicates that hormones regulate the expression of Rspondin-1 (Rspo1). Yet, the regulatory mechanism remains unknown. In the current study, we identify Amphiregulin (Areg) as a novel upstream regulator of Rspo1 expression mediating the hormonal influence. In response to hormonal signaling, Areg emanating from estrogen receptor (ER)-positive luminal cells, induce the expression of Rspo1 in ER-negative luminal cells. The paracrine action of Areg on Rspo1 expression is dependent on Egfr. Our data reveal a novel Estrogen-Areg-Rspo1 regulatory axis in the mammary gland, providing new evidence for the orchestrated action of systemic hormones and local growth factors.


Assuntos
Anfirregulina/fisiologia , Estradiol/fisiologia , Ciclo Estral/fisiologia , Regulação da Expressão Gênica/fisiologia , Glândulas Mamárias Animais/metabolismo , Progesterona/fisiologia , Trombospondinas/biossíntese , Anfirregulina/genética , Animais , Células Cultivadas , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/fisiologia , Cloridrato de Erlotinib/farmacologia , Estradiol/farmacologia , Ciclo Estral/genética , Feminino , Glândulas Mamárias Animais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Cultura Primária de Células , Progesterona/farmacologia , RNA Interferente Pequeno/genética , Trombospondinas/genética , Transcriptoma
5.
Proc Natl Acad Sci U S A ; 116(46): 23132-23142, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31666317

RESUMO

The human endometrium is essential in providing the site for implantation and maintaining the growth and survival of the conceptus. An unreceptive endometrium and disrupted maternal-conceptus interactions can cause infertility due to pregnancy loss or later pregnancy complications. Despite this, the role of uterine glands in first trimester human pregnancy is little understood. An established organoid protocol was used to generate and comprehensively analyze 3-dimensional endometrial epithelial organoid (EEO) cultures from human endometrial biopsies. The derived EEO expand long-term, are genetically stable, and can be cryopreserved. Using endometrium from 2 different donors, EEO were derived and then treated with estrogen (E2) for 2 d or E2 and medroxyprogesterone acetate (MPA) for 6 d. EEO cells were positive for the gland marker, FOXA2, and exhibited appropriate hormonal regulation of steroid hormone receptor expression. Real-time qPCR and bulk RNA-sequencing analysis revealed effects of hormone treatment on gene expression that recapitulated changes in proliferative and secretory phase endometrium. Single-cell RNA sequencing analysis revealed that several different epithelial cell types are present in the EEO whose proportion and gene expression changed with hormone treatment. The EEO model serves as an important platform for studying the physiology and pathology of the human endometrium.


Assuntos
Endométrio/fisiologia , Organoides/metabolismo , Epitélio/fisiologia , Estrogênios/fisiologia , Feminino , Perfilação da Expressão Gênica , Humanos , Organoides/citologia , Progesterona/fisiologia , Análise de Sequência de RNA , Análise de Célula Única
6.
Presse Med ; 48(11 Pt 1): 1244-1248, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31732361

RESUMO

Before menopause, women are protected from the risk of hypertension and atherosclerosis by endogenous estrogens. Estrogens have a vasoprotective role, while progesterone seems to have a neutral effect. Exogenous estrogens used in menopausal treatment have vascular effects. These effects depend of type, dose and administration type, and with age and atherosclerosis stages. Synthetic progestins have varying clinical effects. Each drug must be evaluated separately.


Assuntos
Aterosclerose/prevenção & controle , Estrogênios/farmacologia , Estrogênios/fisiologia , Hipertensão/prevenção & controle , Pré-Menopausa , Progestinas/farmacologia , Artérias/efeitos dos fármacos , Artérias/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Terapia de Reposição de Estrogênios , Etinilestradiol/farmacocinética , Etinilestradiol/farmacologia , Feminino , Humanos , Menopausa/fisiologia , Pré-Menopausa/fisiologia , Progesterona/fisiologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia
7.
Sci Rep ; 9(1): 15495, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664088

RESUMO

The yin and yang of female fertility is a complicated issue; large numbers of women/couples desire fertility and seek assisted reproduction intervention to achieve conception, while others seek to prevent pregnancy. Understanding specific molecules which control endometrial-embryo interactions is essential for both facilitating and preventing pregnancy. SOX17 has recently emerged as an important transcription factor involved in endometrial receptivity and embryo implantation. However, studies to date have examined mouse models of pregnancy which do not necessarily translate to the human. Demonstration of a role for 'implantation factors' in a human system is critical to provide a rationale for in depth clinical investigation and targeting of such factors. We demonstrate that SOX17is present within the receptive human endometrium and is up-regulated within human endometrial epithelial cells by combined estrogen & progesterone, the hormonal milieu during the receptive window. SOX17 localizes to the point of adhesive contact between human endometrial epithelial cells and a human 'embryo mimic' model (trophectodermal spheroid). Targeting SOX17 in endometrial epithelial cells using CRISPR/Cas9 knockdown or a SOX-F family inhibitor, MCC177, significantly inhibited adhesion of an trophectodermal spheroids to the epithelial cells thereby preventing 'implantation'. These data confirm the important role of endometrial SOX17 in human endometrial receptivity and embryo implantation.


Assuntos
Implantação do Embrião/fisiologia , Endométrio/fisiologia , Fatores de Transcrição SOXF/fisiologia , Estrogênios/fisiologia , Feminino , Técnicas de Silenciamento de Genes , Humanos , Gravidez , Progesterona/fisiologia , Fatores de Transcrição SOXF/genética
8.
Orv Hetil ; 160(32): 1247-1259, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31387374

RESUMO

The aim of this review is to explore, in addition to revealing the biological background, new conceptual and therapeutic approaches for reproductive clinicians to provide better and more effective care for sterile and infertile couples. In humans, 75% of unsuccessful pregnancies are the result of failures of implantation, and implantation failure is the limiting factor for in vitro fertilization treatment. A modified "good" inflammation is necessary for implantation and parturition, but for most of pregnancy, inflammation threatens the continuation of pregnancy. During this period, maintaining the non-inflammatory condition is extremely important, enabling the maternal epigenetic effects to occur in the fetus, making it possible for the offspring to adapt as much as possible to the extrauterine life. In the maintenance of the non-inflammatory condition of pregnancy, a large amount of progesterone hormone produced by the placenta (after the luteo-placental shift) plays a crucial role. It has been reported that the role of inflammation during implantation is an ancestral response to the embryo as a foreign body. During normal pregnancy, this inflammation is initiated by the trophoblast and involves the suppression of neutrophil infiltration, the recruitment of natural killer cells to the site of implantation as well as the production of a range of proinflammatory cytokines. During the "implantation window", the uterus is primed to produce several inflammatory signals such as prostaglandin E2 and a range of proinflammatory cytokines, including TNF, IL6 and IFNγ. The feto-placental unit is a semi-foreign graft called a "semi allograft", and the recognition of pregnancy by the mother (host) and the resulting maternal immune tolerance is an essential part of successful pregnancy and the birth of a healthy fetus. Because of the functional or absolute reduction of circulating progesterone (due to the decreasing hormone production of the physiologically "aging" placenta after around the 36th week of pregnancy) progesterone effects become insufficient. Therefore it is unable to suppress the production of IL8 and other inflammatory cytokines and the term inflammation, leading to cervical ripening, uterus contractions and parturition ("good" inflammation). Orv Hetil. 2019; 160(32): 1247-1259.


Assuntos
Parto/fisiologia , Placenta/fisiologia , Manutenção da Gravidez/imunologia , Progesterona/fisiologia , Feminino , Feto , Humanos , Parto/imunologia , Placenta/imunologia , Gravidez , Manutenção da Gravidez/fisiologia , Trofoblastos
9.
Sci Rep ; 9(1): 11816, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413296

RESUMO

Progesterone regulates the endometrium to support pregnancy establishment and maintenance. In the ruminant, one action of progesterone early in pregnancy is to alter embryonic development and hasten the process of trophoblast elongation around day 14-15 of pregnancy, which is required for maternal recognition of pregnancy. Here we demonstrate that the WNT antagonist DKK1, whose expression is increased by progesterone treatment, can act on the bovine embryo during day 5 to 7.5 of development (the morula to blastocyst stage) to promote embryonic elongation on day 15 of pregnancy. Embryos were produced in vitro and exposed to 0 or 100 ng/ml recombinant human DKK1 from day 5 to 7.5 of culture. Blastocysts were transferred into synchronized recipient cows on day 7.5 (n = 23 for control and 17 for DKK1). On day 15, cows were slaughtered and embryos recovered by flushing the uterus. Embryo recovery was n = 11 for controls (48% recovery) and n = 11 for DKK1 (65% recovery). Except for two DKK1 embryos, all embryos were filamentous. Treatment with DKK1 increased (P = 0.007) the length of filamentous embryos from 43.9 mm to 117.4 mm and the intrauterine content of the maternal recognition of pregnancy signal IFNT (P = 0.01) from 4.9 µg to 16.6 µg. Determination of differentially expressed genes (DEG), using the R environment, revealed 473 DEG at p < 0.05 but none at FDR < 0.05, suggesting that DKK1 did not strongly modify the embryo transcriptome at the time it was measured. However, samples clustered apart in a multidimensional scaling analyisis. Weighted gene co-expression analysis of the transcriptome of filamentous embryos revealed a subset of genes that were related to embryo length, with identification of a significant module of genes in the DKK1 group only. Thus, several of the differences between DKK1 and control groups in gene expression were due to differences in embryo length. In conclusion, DKK1 can act on the morula-to-blastocyst stage embryo to modify subsequent trophoblast elongation. Higher pregnancy rates associated with transfer of DKK1-treated embryos may be due in part to enhancements of trophoblast growth and antiluteolytic signaling through IFNT secretion. Given that progesterone can regulate both timing of trophoblast elongation and DKK1 expression, DKK1 may be a mediator of progesterone effects on embryonic development.


Assuntos
Blastocisto/citologia , Embrião de Mamíferos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Mórula/citologia , Progesterona/fisiologia , Trofoblastos/citologia , Animais , Bovinos , Embrião de Mamíferos/citologia , Desenvolvimento Embrionário/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Transcriptoma
10.
Horm Behav ; 115: 104560, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31310761

RESUMO

There have been mixed findings regarding whether raters judge women's natural faces more attractive when the women were photographed near ovulation relative to when photographed in other cycle regions. Bobst and Lobmaier (2012) isolated shape cues associated with ovulatory timing via computer morphing techniques and found that men judged face shapes characteristic of the fertile window as more attractive than those characteristic of the luteal phase. Here, we tested replication of their findings but also added stimuli from the early follicular phase. We constructed three composite faces constructed from photos of the same 23 women who had each been photographed in the early follicular phase, during the fertile window, and during the luteal phase. We next warped 20 other identity faces to the shapes of the composite faces representing each cycle phase, and asked male participants to rank order the resulting face triplets for attractiveness. Men ranked fertile window and luteal phase stimuli as more attractive than early follicular stimuli, but ranked fertile window and luteal phase faces as equally attractive. This result failed to replicate preferences for fertile window over luteal phase stimuli, and thereby argues against perceivers' ability to detect face shape cues of immediate fecundity. Because estradiol was lower in the early follicular phase relative to the other two cycle phases, our findings are consistent with the possibility that within-women increases in estradiol produce subtle increases in face shape attractiveness. Discussion addresses the overall evidence for facial cues of women's ovulatory timing.


Assuntos
Beleza , Estradiol/fisiologia , Face/fisiologia , Ovulação/fisiologia , Progesterona/fisiologia , Percepção Social , Mulheres , Adulto , Reconhecimento Facial/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento Sexual/fisiologia , Adulto Jovem
11.
Horm Behav ; 115: 104553, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31279702

RESUMO

Like many visual stimuli, multi-digit numbers are of a hierarchical nature, with whole number magnitudes depending on individual digit magnitudes. Accordingly, multi-digit numbers can be processed in a holistic (whole number magnitudes) or decomposed manner (digit magnitudes). The compatibility effect during number comparison serves as an indicator of decomposed processing. It is characterized by impaired performance for items where the larger number contains the smaller unit-digit. We were recently able to demonstrate, that the compatibility effect indeed depends on an individual's tendency to process visual hierarchical stimuli on a global or local level. Accordingly, factors affecting global-local processing, should also affect number magnitude processing, i.e. the compatibility effect. Among these factors are hemispheric asymmetries, sex differences and sex hormones (estradiol, progesterone, testosterone). In the present study 39 men and 37 naturally cycling women in their luteal cycle phase completed a number comparison task with stimuli randomly presented to the left and right hemifield. As in previous studies, we observed a larger compatibility effect in the right hemifield (left hemisphere) than in the left hemifield (right hemisphere) and in men than in women. However, this is the first study to evaluate the effects of sex hormones on hemispheric asymmetries during number comparison. We found progesterone to relate to increased hemispheric asymmetries in men, but decreased hemispheric asymmetries in women. Additionally, testosterone was negatively related to hemispheric asymmetries in women's compatibility effect in reaction times. These results add to the growing evidence that sex hormones relate to hemispheric asymmetries in cognitive functions.


Assuntos
Lateralidade Funcional/fisiologia , Conceitos Matemáticos , Progesterona/fisiologia , Caracteres Sexuais , Testosterona/fisiologia , Pensamento/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
13.
Sci Rep ; 9(1): 7716, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118434

RESUMO

Conceptus elongation coincides with one of the periods of greatest pregnancy loss in cattle and is characterized by rapid trophectoderm expansion, commencing ~ Day 13 of pregnancy, i.e. before maternal pregnancy recognition. The process has yet to be recapitulated in vitro and does not occur in the absence of uterine gland secretions in vivo. Moreover, conceptus elongation rates are positively correlated to systemic progesterone in maternal circulation. It is, therefore, a maternally-driven and progesterone-correlated developmental phenomenon. This study aimed to comprehensively characterize the biochemical composition of the uterine luminal fluid on Days 12-14 - the elongation-initiation window - in heifers with normal vs. high progesterone, to identify molecules potentially involved in conceptus elongation initiation. Specifically, nucleotide, vitamin, cofactor, xenobiotic, peptide, and energy metabolite profiles of uterine luminal fluid were examined. A total of 59 metabolites were identified, of which 6 and 3 displayed a respective progesterone and day effect, whereas 16 exhibited a day by progesterone interaction, of which 8 were nucleotide metabolites. Corresponding pathway enrichment analysis revealed that pyridoxal, ascorbate, tricarboxylic acid, purine, and pyrimidine metabolism are of likely importance to to conceptus elongation initiation. Moreover, progesterone reduced total metabolite abundance on Day 12 and may alter the uterine microbiome.


Assuntos
Bovinos/fisiologia , Prenhez/fisiologia , Progesterona/fisiologia , Administração Intravaginal , Animais , Blastocisto , Líquidos Corporais/química , Ciclo do Ácido Cítrico , Coenzimas/análise , Metabolismo Energético/efeitos dos fármacos , Feminino , Troca Materno-Fetal , Microbiota/efeitos dos fármacos , Nucleotídeos/análise , Peptídeos/análise , Gravidez , Prenhez/sangue , Progesterona/administração & dosagem , Progesterona/sangue , Útero/efeitos dos fármacos , Útero/metabolismo , Útero/microbiologia , Vitaminas/análise , Xenobióticos/análise
14.
Endocr Rev ; 40(4): 1152-1162, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074764

RESUMO

Sex steroid estrogens, androgens, and progesterone, produced by the gonads, which have long been considered as endocrine glands, are implicated in sexual differentiation, puberty, and reproduction. However, the impact of sex hormones goes beyond these effects through their role on energy metabolism. Indeed, sex hormones are important physiological regulators of glucose homeostasis and, in particular, of the enteroinsular axis. In this review, we describe the roles of estrogens, androgens, and progesterone on glucose homeostasis through their effects on pancreatic α- and ß-cells, as well as on enteroendocrine L-cells, and their implications in hormonal biosynthesis and secretion. The analysis of their mechanisms of action with the dissection of the receptors implicated in the several protective effects could provide some new aspects of the fine-tuning of hormonal secretion under the influence of the sex. This knowledge paves the way to the understanding of transgender physiology and new potential therapeutics in the field of type 2 diabetes.


Assuntos
Androgênios/metabolismo , Células Enteroendócrinas/metabolismo , Glucose/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Progesterona/metabolismo , Androgênios/fisiologia , Animais , Trato Gastrointestinal/metabolismo , Células Secretoras de Glucagon/metabolismo , Hormônios Esteroides Gonadais/fisiologia , Humanos , Células Secretoras de Insulina/metabolismo , Camundongos , Progesterona/fisiologia , Ratos
15.
Artigo em Inglês | MEDLINE | ID: mdl-31047850

RESUMO

Autoimmune diseases (AIDs) are a heterogeneous group of disorders in terms of clinical manifestations, pathogenesis, and prevalence, and there is no agreement to date on a common classification. Adaptive immune responses are responsible for the existence of AIDs, although innate immunity is also involved in misguiding the immune response against self-antigens. Hormones, in general, and in particular steroid hormones, play a critical role in the physiology and pathology of the immune system, especially in adaptive immunity. Hormonal factors, alone or in relation to age, sex, and reproductive status, are involved in conditioning the onset of a number of AIDs. There is a well-defined sexual dimorphism for human AIDs. At the same time, the classic view has been that steroid hormones have well-defined effects, with one type, estrogens, being "pro-inflammatory" and the other two progestogens (progesterone and its synthetic analogs) and androgens being "anti-inflammatory." Although this view has been considered too simplistic and seems contradicted by numerous observations, it remains valid: progestogens and androgens are immunosuppressive and therefore protective against AIDs, whereas estrogens are immune-stimulatory and therefore pathogenic in AIDs.


Assuntos
Androgênios , Doenças Autoimunes , Estrogênios , Progesterona , Androgênios/fisiologia , Estrogênios/fisiologia , Humanos , Sistema Imunitário , Progesterona/fisiologia
16.
J Pharmacol Sci ; 139(4): 259-265, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30962088

RESUMO

Sex hormones, such as testosterone, progesterone, and 17ß-estradiol, control various physiological functions. This review focuses on the sex hormonal regulation of K+ channels and the effects of such regulation on electrophysiological and contractile functions of muscles. In the cardiac tissue, testosterone and progesterone shorten action potential, and estrogen lengthens QT interval, a marker of increased risk of ventricular tachyarrhythmias. We have shown that testosterone and progesterone in physiological concentration activate KCNQ1 channels via membrane-delimited sex hormone receptor/eNOS pathways to shorten the action potential duration. Mitochondrial K+ channels are also involved in the protection of cardiac muscle. Testosterone and 17ß-estradiol directly activate mitochondrial inner membrane K+ channels (Ca2+ activated K+ channel (KCa channel) and ATP-sensitive K+ channel (KATP channel)) that are involved in ischemic preconditioning and cardiac protection. During pregnancy, uterine blood flow increases to support fetal growth and development. It has been reported that 17ß-estradiol directly activates large-conductance Ca2+-activated K+ channel (BKCa channel) attenuating arterial contraction. Furthermore, 17ß-estradiol increases expression of BKCa channel ß1 subunit which enhances BKCa channel activity by DNA demethylation. These findings are useful for understanding the mechanisms of sex or generation-dependent differences in the physiological and pathological functions of muscles, and the mechanisms of drug actions.


Assuntos
Fenômenos Eletrofisiológicos/fisiologia , Estradiol/fisiologia , Contração Muscular/fisiologia , Músculos/metabolismo , Músculos/fisiologia , Canais de Potássio/metabolismo , Canais de Potássio/fisiologia , Progesterona/fisiologia , Testosterona/fisiologia , Animais , Humanos
17.
Clin Transl Gastroenterol ; 10(3): e00009, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30908306

RESUMO

The disease course of autoimmune diseases such as rheumatoid arthritis is altered during pregnancy, and a similar modulatory role of pregnancy on inflammatory bowel disease (IBD) has been proposed. Hormonal, immunological, and microbial changes occurring during normal pregnancy may interact with the pathophysiology of IBD. IBD consists of Crohn's disease and ulcerative colitis, and because of genetic, immunological, and microbial differences between these disease entities, they may react differently during pregnancy and should be described separately. This review will address the pregnancy-induced physiological changes and their potential effect on the disease course of ulcerative colitis and Crohn's disease, with emphasis on the modulation of epithelial barrier function and immune profiles by pregnancy hormones, microbial changes, and microchimerism.


Assuntos
Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Gravidez/fisiologia , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Estrogênios/fisiologia , Feminino , Humanos , Mucosa Intestinal/fisiologia , Gravidez/imunologia , Progesterona/fisiologia
18.
Theriogenology ; 129: 54-60, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30818252

RESUMO

Despite modifications in techniques and protocols used for multiple ovulation embryo transfer in recent decades, transferrable quality embryos (TQE) has remained relatively unchanged. The objective of this study was to evaluate the effects of endogenous progesterone during beef cow superstimulation on embryo quality and quantity. Thirty non-pregnant beef cows were sorted into 1 of 5 replicates and randomly assigned to one of two groups: High Progesterone (HP) or Low Progesterone (LP). All cows, were pre-synchronized utilizing a 5-d CO-Synch + CIDR protocol. Nine days after estrus (d 0) with a corpus luteum present, all cows received ultrasound-guided dominant follicle ablation (DFA) and were administered a CIDR with LP cows also being administered PGF2α. All cows began a timed, 13-d, superovulation CIDR-based protocol and were artificially inseminated (AI) twice. Embryo were recovered and evaluated on each replicate 7 days after first AI. Blood samples were collected to evaluate progesterone (P4) and estradiol concentrations daily when cows were handled. Greater number of total embryos were recovered from the HP than the LP cows (19.26 vs. 10.74, P = 0.01). The HP cows also had greater number Stage 4 embryos along with more Quality Grade 3 and 4 embryos than the LP group (5.76 vs 2.20 P = 0.002; 1.87 vs 0.61, P = 0.01; 8.22 vs 2.89, P = 0.01, respectively). However, LP cows had a greater percentage overall of freezable embryos with a higher percentage of Grade 1 embryos (58.22 vs 37.32, P = 0.03) and a greater percentage of Stage 7 and 6 TQEs (18.47 vs 1.22, P = 0.01; 10.37 vs 3.19, P = 0.03). Serum P4 concentrations were greater on d 2-3 in the HP cows (P = 0.002). In addition, HP cows had greater concentrations of estradiol (P < 0.0001) on d 6. Comparatively, estradiol was greater in concentration in the LP cows (P ≤ 0.04) on d 2-4. In conclusion, removal of endogenous progesterone during superovulation may decrease the total number of embryos but increase the percentage of Grade 1 embryos and percentage of Stage 6 and 7 TQE in a single recovery.


Assuntos
Bovinos/fisiologia , Embrião de Mamíferos/efeitos dos fármacos , Indução da Ovulação/veterinária , Progesterona/fisiologia , Animais , Desenvolvimento Embrionário , Feminino , Ovário/efeitos dos fármacos , Indução da Ovulação/métodos , Progesterona/sangue
19.
Respir Physiol Neurobiol ; 263: 55-61, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30880277

RESUMO

The steroid hormone progesterone is well-known for its role in neuroprotection, in the pre- and postnatal brain development, and is also recognized as a potent respiratory stimulant that reduces the frequency of sleep apnea in adult female subjects. Over the past few years, we have used newborn rats or mice to provide convincing evidence that the respiratory effect of progesterone involves a balance between excitation mediated by progesterone receptors, and an inhibition due to the fast conversion of progesterone to allopregnanolone, a positive allosteric modulator of GABAA receptors. This review focuses on the sex- and age- specific roles of nuclear and membrane progesterone receptors (nPR or mPR), and highlight the clinical potential of these receptors for the treatment of apnea of prematurity. We present original data showing that in newborn rats, selective nPR or mPR agonists are more efficient to reduce apnea frequency at postnatal days 12 than at postnatal day 1, and appear more efficient in males than in females. Furthermore, new results obtained by using intra-cisternal injection of specific siRNA targeting mPRα, mPRß (two mPR with high brain expression) or nPR suggest that mPRß regulates the stability of the breathing pattern in males, while effects of nPR appear in females. While several important questions remain to be addressed before a safe clinical use could be proposed, these results highlight the potential role of these drugs as complementary, and sex-specific tools for the treatment of apnea in preterm neonates.


Assuntos
Animais Recém-Nascidos/fisiologia , Apneia/metabolismo , Progesterona/fisiologia , Receptores de Progesterona/fisiologia , Respiração , Caracteres Sexuais , Animais , Animais Recém-Nascidos/metabolismo , Feminino , Masculino , Progesterona/metabolismo , Ratos , Receptores de Progesterona/metabolismo
20.
Theriogenology ; 128: 81-90, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30743107

RESUMO

Aluteal cycles were induced in the mare to evaluate the effects of progesterone deprivation on the gene expression of embryos and endometrium collected eight days after ovulation. We hypothesized that the transcript expression would be altered during induced aluteal (AL) cycles (low progesterone <1 ng/mL) when compared with control cycles during diestrus (high progesterone; > 4 ng/mL) for 1) the embryonic expression of progesterone-mediated transcripts and those related to normal embryo growth and development and 2) the endometrial expression of progesterone-mediated transcripts and those related to prostaglandin synthesis and normal pregnancy establishment. Seven cyclic mares with a median age of 6.5 years (range 3-16) were utilized in a crossover design. Mares in estrus were artificially inseminated to a fertile stallion and randomly assigned to control or AL groups. Mares received either saline solution (control mares) or PGF2α (AL mares), twice daily on days 0, 1, and 2 and once daily on days 3 and 4. Serial blood samples were collected daily from day 0 (ovulation) until the day of embryo collection and endometrial biopsy on day 8. Mares were monitored until they returned to estrus, and artificially inseminated. Mares were switched to the opposite treatment group only after a successful embryo collection occurred during the previous cycle and only cycles that produced embryos were used for analyses. The study design resulted in paired samples from each mare for analyses. No significant rise in progesterone was observed in the AL group with mean concentrations of plasma progesterone remaining <1.0 ng/mL from ovulation until embryo collection on day 8. This is in sharp contrast to the control (luteal) cycle where a post-ovulatory rise in plasma progesterone was observed. Real-time RT-PCR was utilized to evaluate the expression of ESR1, PGR, CYP19A1, P19, SLC35A1, OCD, APOB, AQP3, NEU2 transcripts in the embryos and PTGS2, P19, ESR1, HK2, sPLA2, PGR, CTGF, IFNE, FGF9, SLC36A2 expression in the endometrium. Four transcripts showed increased expressed in embryos developed during AL cycles ESR1, P19, APOB and PGR (p < 0.05). Four transcripts showed increased expressed in endometrium developed during AL cycles sPLA2, PGR, ESR1, FGF9 (p < 0.05) and four transcripts showed decreased expression P19, CTGF, IFNE, HK2 (p < 0.05). Additionally, staining differences were present in endometrial staining for both ERα and PR receptor during AL cycles compared with control cycles. Embryos and endometrium developed in a progesterone-deprived environment during induced aluteal cycles demonstrated altered transcript expression. These results indicate that adequate progesterone levels may be a key mediator of the appropriate embryo-maternal environment during early preimplantation embryo development.


Assuntos
Embrião de Mamíferos/metabolismo , Endométrio/metabolismo , Cavalos/embriologia , Animais , Desenvolvimento Embrionário , Ciclo Estral , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Cavalos/metabolismo , Inseminação Artificial/veterinária , Progesterona/fisiologia
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