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1.
Physiol Rev ; 104(3): 1121-1145, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38329421

RESUMO

Parturition is a complex physiological process that must occur in a reliable manner and at an appropriate gestation stage to ensure a healthy newborn and mother. To this end, hormones that affect the function of the gravid uterus, especially progesterone (P4), 17ß-estradiol (E2), oxytocin (OT), and prostaglandins (PGs), play pivotal roles. P4 via the nuclear P4 receptor (PR) promotes uterine quiescence and for most of pregnancy exerts a dominant block to labor. Loss of the P4 block to parturition in association with a gain in prolabor actions of E2 are key transitions in the hormonal cascade leading to parturition. P4 withdrawal can occur through various mechanisms depending on species and physiological context. Parturition in most species involves inflammation within the uterine tissues and especially at the maternal-fetal interface. Local PGs and other inflammatory mediators may initiate parturition by inducing P4 withdrawal. Withdrawal of the P4 block is coordinated with increased E2 actions to enhance uterotonic signals mediated by OT and PGs to promote uterine contractions, cervix softening, and membrane rupture, i.e., labor. This review examines recent advances in research to understand the hormonal control of parturition, with focus on the roles of P4, E2, PGs, OT, inflammatory cytokines, and placental peptide hormones together with evolutionary biology of and implications for clinical management of human parturition.


Assuntos
Parto , Parto/fisiologia , Humanos , Feminino , Gravidez , Animais , Progesterona/metabolismo , Progesterona/fisiologia , Ocitocina/metabolismo , Ocitocina/fisiologia , Útero/metabolismo , Útero/fisiologia , Prostaglandinas/metabolismo , Estradiol/metabolismo
2.
Cancer Rep (Hoboken) ; 7(1): e1934, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38013666

RESUMO

BACKGROUND: Progesterone therapy is a relatively inexpensive treatment option for endometrial and breast cancers, with few side effects. Two signaling pathways usually mediate the physiological effects of progesterone, namely genomic and non-genomic actions. Genomic action occurs slowly via the nuclear progesterone receptor (PR), whereas the membrane progesterone receptor (mPR) induces rapid non-genomic action. AIMS: We investigated the effects of progesterone and various PR agonists on ovarian cancer cells. METHODS AND RESULTS: PR expression of six serous ovarian cancer cell lines was examined by western blotting, and mPR expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). PR-negative and mPR-positive ovarian cancer cells were exposed to progesterone and seven types of PR agonists (medroxyprogesterone acetate [MPA], dehydroepiandrosterone, dienogest, levonorgestrel, drospirenone, pregnenolone, and allopregnanolone) at 10-400 µM, and viable cell counts after exposure for 30 min were measured using the water-soluble tetrazolium (WST-1) assay. Ovarian cancer cell lines were exposed to 100 µM progesterone, and the expression of BAX, a pro-apoptotic protein, after 1-5 min was examined by western blotting. Western blotting detected no PR expression in the six serous ovarian cancer cell lines. In contrast, RT-qPCR detected mPR expression in all six serous ovarian cancer cell lines. Progesterone and MPA-induced cell death in all tested ovarian cancer cell lines in a concentration-dependent manner, whereas no effect was observed for other PR agonists. Western blotting revealed that pro-apoptotic protein BAX expression occurred 1 min after exposure to progesterone, suggesting that the cytocidal effects are mediated by rapid non-genomic action. CONCLUSION: Progesterone and MPA exhibited a rapid cytocidal effect on PR-negative ovarian cancer cells through non-genomic action. Progesterone and MPA could be novel adjuvant therapies for ovarian cancer.


Assuntos
Neoplasias Ovarianas , Progesterona , Feminino , Humanos , Progesterona/farmacologia , Progesterona/fisiologia , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Proteína X Associada a bcl-2 , Progestinas/farmacologia , Acetato de Medroxiprogesterona/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Genômica , Morte Celular
3.
Science ; 382(6666): 76-81, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37797007

RESUMO

During pregnancy, physiological adaptations prepare the female body for the challenges of motherhood. Becoming a parent also requires behavioral adaptations. Such adaptations can occur as early as during pregnancy, but how pregnancy hormones remodel parenting circuits to instruct preparatory behavioral changes remains unknown. We found that action of estradiol and progesterone on galanin (Gal)-expressing neurons in the mouse medial preoptic area (MPOA) is critical for pregnancy-induced parental behavior. Whereas estradiol silences MPOAGal neurons and paradoxically increases their excitability, progesterone permanently rewires this circuit node by promoting dendritic spine formation and recruitment of excitatory synaptic inputs. This MPOAGal-specific neural remodeling sparsens population activity in vivo and results in persistently stronger, more selective responses to pup stimuli. Pregnancy hormones thus remodel parenting circuits in anticipation of future behavioral need.


Assuntos
Estradiol , Comportamento Materno , Poder Familiar , Área Pré-Óptica , Progesterona , Animais , Feminino , Camundongos , Gravidez , Estradiol/fisiologia , Comportamento Materno/fisiologia , Comportamento Materno/psicologia , Poder Familiar/psicologia , Área Pré-Óptica/citologia , Área Pré-Óptica/fisiologia , Progesterona/fisiologia , Modelos Animais , Neurônios/metabolismo , Neurônios/fisiologia
4.
Science ; 382(6666): 33-34, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37797022

RESUMO

Progesterone and estrogen exert separate effects on the brains of pregnant mice.


Assuntos
Encéfalo , Estrogênios , Comportamento Materno , Poder Familiar , Progesterona , Animais , Feminino , Camundongos , Gravidez , Estrogênios/fisiologia , Progesterona/fisiologia
5.
J Reprod Dev ; 69(3): 147-153, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-36935121

RESUMO

Progesterone (P) enhances spermatozoal hyperactivation, a capacitation event. Hyperactivation is associated with successful in vitro fertilization (IVF). In this study, we examined the effects of P on hyperactivation and IVF in mice. P enhanced spermatozoal hyperactivation and increased IVF success rate in a dose-dependent manner. Moreover, P affected spermatozoal hyperactivation and IVF through the membrane progesterone receptor of the spermatozoal head. These results show that P regulates spermatozoal capacitation and fertilization in mice. The concentration of P changes during the estrous cycle, indicating that spermatozoa are capacitated in response to the oviductal environment and subsequently fertilize the oocyte.


Assuntos
Progesterona , Capacitação Espermática , Masculino , Animais , Camundongos , Progesterona/farmacologia , Progesterona/fisiologia , Sêmen , Fertilização in vitro/métodos , Espermatozoides/fisiologia , Fertilização , Motilidade dos Espermatozoides
6.
Sci Rep ; 13(1): 2164, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750584

RESUMO

Progesterone and its receptors (PRs) participate in mating and reproduction, but their role in spatial declarative memory is not understood. Male mice expressed PRs, predominately in excitatory neurons, in brain regions that support spatial memory, such as the hippocampus and entorhinal cortex (EC). Furthermore, segesterone, a specific PR agonist, activates neurons in both the EC and hippocampus. We assessed the contribution of PRs in promoting spatial and non-spatial cognitive learning in male mice by examining the performance of mice lacking this receptor (PRKO), in novel object recognition, object placement, Y-maze alternation, and Morris-Water Maze (MWM) tasks. In the recognition test, the PRKO mice preferred the familiar object over the novel object. A similar preference for the familiar object was also seen following the EC-specific deletion of PRs. PRKO mice were also unable to recognize the change in object position. We confirmed deficits in spatial memory of PRKO mice by testing them on the Y-maze forced alternation and MWM tasks; PR deletion affected animal's performance in both these tasks. In contrast to spatial tasks, PR removal did not alter the response to fear conditioning. These studies provide novel insights into the role of PRs in facilitating spatial, declarative memory in males, which may help with finding reproductive partners.


Assuntos
Sistema Límbico , Aprendizagem em Labirinto , Receptores de Progesterona , Memória Espacial , Animais , Masculino , Camundongos , Córtex Entorrinal/fisiologia , Hipocampo/fisiologia , Sistema Límbico/fisiologia , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/fisiopatologia , Progesterona/fisiologia , Receptores de Progesterona/fisiologia , Memória Espacial/fisiologia
7.
Front Neuroendocrinol ; 69: 101060, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36758768

RESUMO

In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.


Assuntos
Progesterona , Progestinas , Animais , Humanos , Progestinas/farmacologia , Progesterona/fisiologia , Anticoncepcionais , Estudos Transversais , Congêneres da Progesterona , Encéfalo/diagnóstico por imagem
8.
Int J Mol Sci ; 23(14)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35887338

RESUMO

Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, various novel actions of this interesting steroid have been documented, of which its neuro- and immunoprotective activities are the most widely discussed. Discoveries of the novel biological activities of progesterone have also driven research and development in the field of progesterone analogues used in human medicine. Progestogen treatment has traditionally and predominately been used in maintaining pregnancy, the prevention of preterm labor, various gynecological pathologies, and in lowering the negative effects of menopause. However, there are also various other medical fields where progesterone and its analogues could find application in the future. The aim of this work is to show the mechanisms of action of progesterone and its metabolites, the physiological and pharmacological actions of progesterone and its synthetic analogues in human medicine, as well as the impacts of its production and use on the environment.


Assuntos
Progesterona , Progestinas , Feminino , Hormônios , Humanos , Recém-Nascido , Gravidez , Progesterona/farmacologia , Progesterona/fisiologia , Progestinas/farmacologia , Progestinas/uso terapêutico
9.
Endocr Rev ; 43(4): 720-742, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34791092

RESUMO

Rapid effects of steroid hormones were discovered in the early 1950s, but the subject was dominated in the 1970s by discoveries of estradiol and progesterone stimulating protein synthesis. This led to the paradigm that steroid hormones regulate growth, differentiation, and metabolism via binding a receptor in the nucleus. It took 30 years to appreciate not only that some cellular functions arise solely from membrane-localized steroid receptor (SR) actions, but that rapid sex steroid signaling from membrane-localized SRs is a prerequisite for the phosphorylation, nuclear import, and potentiation of the transcriptional activity of nuclear SR counterparts. Here, we provide a review and update on the current state of knowledge of membrane-initiated estrogen (ER), androgen (AR) and progesterone (PR) receptor signaling, the mechanisms of membrane-associated SR potentiation of their nuclear SR homologues, and the importance of this membrane-nuclear SR collaboration in physiology and disease. We also highlight potential clinical implications of pathway-selective modulation of membrane-associated SR.


Assuntos
Receptores de Progesterona , Receptores de Esteroides , Androgênios , Estradiol , Estrogênios , Humanos , Progesterona/fisiologia , Receptores Androgênicos , Receptores de Progesterona/metabolismo , Receptores de Esteroides/metabolismo , Esteroides
10.
Endocrinology ; 163(3)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34918063

RESUMO

Successful lactation and the risk for developing breast cancer depend on growth and differentiation of the mammary gland (MG) epithelium that is regulated by ovarian steroids (17ß-estradiol [E] and progesterone [P]) and pituitary-derived prolactin (PRL). Given that the MG of pigs share histomorphogenic features present in the normal human breast, we sought to define the transcriptional responses within the MG of pigs following exposure to all combinations of these hormones. Hormone-ablated female pigs were administered combinations of E, medroxyprogesterone 17-acetate (source of P), and either haloperidol (to induce PRL) or 2-bromo-α-ergocryptine. We subsequently monitored phenotypic changes in the MG including mitosis, receptors for E and P (ESR1 and PGR), level of phosphorylated STAT5 (pSTAT5), and the frequency of terminal ductal lobular unit (TDLU) subtypes; these changes were then associated with all transcriptomic changes. Estrogen altered the expression of approximately 20% of all genes that were mostly associated with mitosis, whereas PRL stimulated elements of fatty acid metabolism and an inflammatory response. Several outcomes, including increased pSTAT5, highlighted the ability of E to enhance PRL action. Regression of transcriptomic changes against several MG phenotypes revealed 1669 genes correlated with proliferation, among which 29 were E inducible. Additional gene expression signatures were associated with TDLU formation and the frequency of ESR1 or PGR. These data provide a link between the hormone-regulated genome and phenome of the MG in a species having a complex histoarchitecture like that in the human breast, and highlight an underexplored synergy between the actions of E and PRL during MG development.


Assuntos
Estrogênios/fisiologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Progesterona/fisiologia , Prolactina/fisiologia , Porco Miniatura/fisiologia , Transcriptoma/fisiologia , Animais , Bromocriptina/administração & dosagem , Sinergismo Farmacológico , Estradiol/administração & dosagem , Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/genética , Estrogênios/deficiência , Feminino , Haloperidol/administração & dosagem , Glândulas Mamárias Animais/química , Glândulas Mamárias Animais/efeitos dos fármacos , Acetato de Medroxiprogesterona/administração & dosagem , Modelos Animais , Morfogênese/efeitos dos fármacos , Morfogênese/genética , Ovariectomia , Progesterona/deficiência , Prolactina/deficiência , Receptores de Progesterona/análise , Receptores de Progesterona/genética , Suínos , Transcriptoma/efeitos dos fármacos
11.
Int J Mol Sci ; 22(20)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34681696

RESUMO

The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means "promoting gestation", this steroid hormone is far more than a gestational agent. Progesterone is recognized as a key physiological component of not only the menstrual cycle and pregnancy but also as an essential steroidogenic precursor of other gonadal and non-gonadal hormones such as aldosterone, cortisol, estradiol, and testosterone. Based on current findings, progesterone and novel progesterone-based drugs have many important functions, including contraception, treatment of dysfunctional uterine bleeding, immune response, and prevention of cancer. Considering the above, reproduction and life are not possible without progesterone; thus, a better understanding of this essential molecule could enable safe and effective use of this hormone in many clinical conditions.


Assuntos
Progesterona/fisiologia , Aborto Espontâneo/tratamento farmacológico , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Sistema Imunitário/metabolismo , Ciclo Menstrual/fisiologia , Gravidez , Síndrome Pré-Menstrual/metabolismo , Síndrome Pré-Menstrual/patologia , Progesterona/uso terapêutico , Triptofano/metabolismo
12.
Acta Biochim Biophys Sin (Shanghai) ; 53(10): 1333-1341, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34343226

RESUMO

Endometrial dysfunction is an important factor for implantation failure. The function of the endometrium is regulated by multiple factors like sex hormones and circadian rhythms. Endometrial stromal cells (ESCs) are a major cellular component in the endometrium, which is essential for proper physiological activities of the endometrium and the establishment of pregnancy. Melatonin, as a circadian-controlled hormone, plays beneficial roles in the regulation of reproductive processes. MT1, a melatonin receptor, can regulate cell proliferation and apoptosis. Whether melatonin-MT1 signal affects biological function of ESCs remains unknown. Here, we showed that MT1 was expressed in human ESCs (hESCs), which could be regulated by estrogen and progesterone. MT1 knockdown inhibited proliferative activity and promoted apoptosis of hESCs by activating caspase-3 and upregulating the Bax/Bcl2 ratio. Melatonin could reverse the effect of MT1 knockdown on proliferative activity and apoptosis of hESCs. Melatonin could promote proliferative activity of hESCs via the JNK/P38 signal pathway and repress the apoptosis of hESCs via the JNK signal pathway. Moreover, in vivo experiments showed that MT1 expression was decreased in endometrial cells from mice with disrupted circadian rhythm, accompanied by increased apoptosis and suppressed proliferative activity, which could be alleviated by administration of melatonin. These results showed the regulatory effect of melatonin-MT1 signal on biological behaviors of ESCs, which might provide a novel therapeutic strategy for endometrial dysfunction induced by disrupted circadian rhythm.


Assuntos
Endométrio/metabolismo , Melatonina/farmacologia , Receptor MT1 de Melatonina/metabolismo , Células Estromais/metabolismo , Adulto , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Ritmo Circadiano , Modelos Animais de Doenças , Endométrio/citologia , Endométrio/efeitos dos fármacos , Estrogênios/fisiologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Progesterona/fisiologia , Receptor MT1 de Melatonina/agonistas , Receptor MT1 de Melatonina/genética , Células Estromais/efeitos dos fármacos , Regulação para Cima/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Psychoneuroendocrinology ; 131: 105285, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34090137

RESUMO

Previous research indicates that worry is associated with poorer working memory performance. Moreover, prior work demonstrates that estradiol relates to both worry and working memory performance. In the present study, we sought to further examine interrelations between worry, estradiol and working memory by testing whether estradiol moderates the association between worry and working memory in females. We hypothesized that worry would be associated with poorer working memory performance at higher levels of estradiol. We also conducted exploratory analyses to examine the role of progesterone as a moderator of the association between worry and working memory. Participants were 97 naturally-cycling females who attended four lab sessions across their menstrual cycles. Consistent with predictions, higher average levels of worry were associated with lower working memory accuracy on particularly difficult trials when average levels of estradiol were also high. The same association between higher worry and lower working memory accuracy emerged when average levels of progesterone were high. Findings highlight the importance of considering ovarian hormones in future studies and current theories of anxiety and cognition.


Assuntos
Ansiedade , Estradiol , Memória de Curto Prazo , Progesterona , Ansiedade/metabolismo , Ansiedade/psicologia , Estradiol/metabolismo , Estradiol/fisiologia , Feminino , Humanos , Memória de Curto Prazo/fisiologia , Ciclo Menstrual/fisiologia , Progesterona/metabolismo , Progesterona/fisiologia
14.
Gynecol Endocrinol ; 37(8): 725-729, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33974468

RESUMO

AIM: Study the effect of low-dose aspirin on the endometrial receptivity in endometriosis rat models. MATERIALS AND METHODS: This study is to explore the expressions of progesterone receptor and LIF among three groups of endometriosis rat models: control group (n = 12), EMs group (n = 15), and aspirin group (n = 17). The expressions of progesterone receptor (PR), PRA, PRB, and leukemia inhibitory factor receptor (LIFR) in eutopic endometrium were determined using immunohistochemistry technology, western blot, and qRT-PCR. The levels of LIF in eutopic endometrium and serum were detected by western blot, qRT-PCR, and ELISA. RESULTS: The expressions of PR, PRA, and PRB protein were significantly increased in the eutopic endometrium after low-dose aspirin treatment, and the level of PRB mRNA was also increased while the ratio of PRA/PRB mRNA was decreased in the eutopic endometrium. The levels of LIF in eutopic endometrium and serum were increased compared with the untreated endometriosis rats. However, the expression of LIFR was not statistically different among the three groups. CONCLUSIONS: The results suggest that the low-dose aspirin treatment could downregulate progesterone resistance and increase the expression of LIF of endometriosis rats during the implantation window, which could improve endometrial receptivity and enhance the pregnant rate of endometriosis. It may provide a potential treatment method for endometriosis-related infertility.


Assuntos
Aspirina/administração & dosagem , Implantação do Embrião/fisiologia , Endometriose/tratamento farmacológico , Fator Inibidor de Leucemia/efeitos dos fármacos , Progesterona/fisiologia , Receptores de Progesterona/análise , Animais , Endometriose/complicações , Endometriose/metabolismo , Endométrio/química , Feminino , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Fator Inibidor de Leucemia/análise , Fator Inibidor de Leucemia/fisiologia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/análise , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/fisiologia , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de Progesterona/efeitos dos fármacos
15.
Brain Res ; 1763: 147448, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33771519

RESUMO

BACKGROUND: Sex hormones have been implicated in pH regulation of numerous physiological systems. One consistent factor of these studies is the sodium-hydrogen exchanger 1 (NHE1). NHE1 has been associated with pH homeostasis at epithelial barriers. Hormone fluctuations have been implicated in protection and risk for breaches in blood brain barrier (BBB)/blood endothelial barrier (BEB) integrity. Few studies, however, have investigated BBB/BEB integrity in neurological disorders in the context of sex-hormone regulation of pH homeostasis. METHODS//RESULTS: Physiologically relevant concentrations of 17-ß-estradiol (E2, 294 pM), progesterone (P, 100 nM), and testosterone (T,3.12 nM) were independently applied to cultured immortalized bEnd.3 brain endothelial cells to study the BEB. Individual gonadal hormones showed preferential effects on extracellular pH (E2), 14C-sucrose uptake (T), stimulated paracellular breaches (P) with dependence on functional NHE1 expression without impacting transendothelial resistance (TEER) or total protein expression. While total NHE1 expression was not changed as determined via whole cell lysate and subcellular fractionation experiment, biotinylation of NHE1 for surface membrane expression showed E2 reduced functional expression. Quantitative proteomic analysis revealed divergent effects of 17-ß-estradiol and testosterone on changes in protein abundance in bEnd.3 endothelial cells as compared to untreated controls. CONCLUSIONS: These data suggest that circulating levels of sex hormones may independently control BEB integrity by 1) regulating pH homeostasis through NHE1 functional expression and 2) modifying the endothelial proteome.


Assuntos
Barreira Hematoencefálica/metabolismo , Estradiol/fisiologia , Progesterona/fisiologia , Trocador 1 de Sódio-Hidrogênio/metabolismo , Testosterona/fisiologia , Animais , Transporte Biológico , Células Endoteliais/metabolismo , Estradiol/sangue , Concentração de Íons de Hidrogênio , Progesterona/sangue , Proteoma/metabolismo , Ratos , Testosterona/sangue
16.
Int J Mol Sci ; 22(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671517

RESUMO

Recently, it has been suggested that progesterone affects the contractile activity of pregnant myometrium via nongenomic pathways; therefore, we aimed to clarify whether progesterone causes and/or inhibits pregnant myometrial contractions via nongenomic pathways. Our in vitro experiments using myometrial strips obtained from rats at 20 days of gestation revealed that progesterone caused myometrial contractions in a concentration- and time-dependent manner at concentrations up to 5 × 10-7 M; however, this effect decreased at concentrations higher than 5 × 10-5 M. Similarly, progesterone enhanced oxytocin-induced contractions up to 5 × 10-7 M and inhibited contractions at concentrations higher than 5 × 10-5 M. Conversely, progesterone did not enhance high-KCl-induced contractions but inhibited contractions in a concentration- and time-dependent manner at concentrations higher than 5 × 10-7 M. We also found that RU486 did not affect progesterone-induced contractions or the progesterone-induced inhibition of high-KCl-induced contractions; however, progesterone-induced contractions were blocked by calcium-free phosphate saline solution, verapamil, and nifedipine. In addition, FPL64176, an activator of L-type voltage-dependent calcium channels, enhanced high-KCl-induced contractions and rescued the decrease in high-KCl-induced contractions caused by progesterone. Together, these results suggest that progesterone exerts conflicting nongenomic effects on the contractions of pregnant myometrium via putative L-type voltage-dependent calcium channels.


Assuntos
Miométrio/fisiologia , Progesterona/fisiologia , Contração Uterina/fisiologia , Animais , Agonistas dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/metabolismo , Feminino , Antagonistas de Hormônios/farmacologia , Mifepristona/farmacologia , Miométrio/efeitos dos fármacos , Nifedipino/farmacologia , Técnicas de Cultura de Órgãos , Ocitocina/farmacologia , Cloreto de Potássio/farmacologia , Gravidez , Progesterona/farmacologia , Pirróis/farmacologia , Ratos Wistar , Contração Uterina/efeitos dos fármacos , Verapamil/farmacologia
17.
Folia Med Cracov ; 60(2): 81-95, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-33252597

RESUMO

BACKGROUND: Uterine leiomyoma is the most widespread benign tumor affecting women of childbearing age. There are still gaps in the understanding of its pathogenesis. Telocytes are unique cells found in more than 50 different locations inside the human body. The functional relationship between cells could clarify the pathogenesis of leiomyomata. Examination of membrane receptors on telocytes could explain their role in fibrosis, oxidative stress, and myometrial contractility. AIM: This research was conducted to assess the density of telocytes in terms of their putative role in leiomyoma formation by focusing on their correlation with the expression of estrogen and progesterone receptors. METHODS: For gross evaluation of uterine tissue samples from leiomyoma, routine histology of adjacent and unaffected myometrium was performed. Immunohistochemical analysis of c-kit, tryptase, CD34, PDGFRα (telocyte-specific), and ER and PRs (estrogen and progesterone receptors) was performed to examine uterine telocytes and the expression of sex steroid receptors. RESULTS: The decline in telocyte density in leiomyoma foci was correlated with high progesterone expression and low estrogen receptor expression. The unchanged myometrium showed the opposite correlation and balance between both steroid hormone receptors. The difference in sex steroid receptor expression is correlated with the density of uterine telocytes, which emphasizes their conductor function. CONCLUSIONS: A reduction in telocyte density and the changes in examined marker expression demonstrate the involvement of telocytes in local homeostasis. The expression of membrane receptors explicitly indicates their functional potential in the human myometrium, focusing attention on contractility and local homeostasis.


Assuntos
Congêneres do Estradiol/farmacocinética , Leiomioma/diagnóstico por imagem , Leiomioma/patologia , Progesterona/farmacocinética , Telócitos/efeitos dos fármacos , Telócitos/fisiologia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Adulto , Idoso , Congêneres do Estradiol/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Polônia , Progesterona/fisiologia
18.
Sci Rep ; 10(1): 16316, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33005004

RESUMO

Hepatic gluconeogenesis is the main pathway for blood glucose maintenance activated during fasting. Retardation of insulin action, such as in diabetes mellitus, activates gluconeogenesis during the fed state. While the role of progesterone (P4) in diabetes is controversial, the P4 receptor, progesterone receptor membrane component 1 (PGRMC1), is known to stimulate pancreatic insulin secretion. We investigated the role of P4, via hepatic PGRMC1, during gluconeogenesis. The PGRMC1 binding chemical, AG-205, induced PGRMC1 monomer (25 kDa) abundance, and increased PEPCK expression and glucose production in parallel with cyclic AMP (cAMP) induction in Hep3B cells. PGRMC1-mediated cyclic AMP was inhibited by an adenylate cyclase inhibitor (MDL-12,330A). PEPCK suppression in Pgrmc1 KO hepatocyte was not observed after treatment of MDL-12,330A. PGRMC1 knockdown or overexpression systems in Hep3B cells confirmed that PGRMC1 mediates PEPCK expression via phosphorylation of cAMP-response element binding protein (CREB). CREB phosphorylation and PEPCK expression in primary hepatocytes were greater than that in PGRMC1 knock-out hepatocytes. Progesterone increased PGRMC1 expression, which induced cAMP and PEPCK induction and glucose production. In vivo, P4 suppressed gluconeogenesis following plasma insulin induction under normal conditions in a mouse model. However, P4 increased blood glucose via gluconeogenesis in parallel with increases in PGRMC1 and PEPCK expression in mice in both insulin-deficient and insulin-resistant conditions. We conclude that P4 increases hepatic glucose production via PGRMC1, which may exacerbate hyperglycaemia in diabetes where insulin action is limited.


Assuntos
Glicemia/metabolismo , Hepatócitos/metabolismo , Insulina/metabolismo , Proteínas de Membrana/metabolismo , Progesterona/metabolismo , Receptores de Progesterona/metabolismo , Adenilil Ciclases/metabolismo , Animais , Western Blotting , Linhagem Celular , AMP Cíclico/metabolismo , Gluconeogênese , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Mitocondriais , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Progesterona/fisiologia , Reação em Cadeia da Polimerase em Tempo Real
19.
Psychoneuroendocrinology ; 122: 104882, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33068952

RESUMO

Ovarian hormones exert an influence on social information processing, in which, however, the exact roles of estradiol and progesterone remain unclear. This study examines the specific influences of these two ovarian hormones on social information processing across the menstrual cycle using the emotional face flanker task and attentional network test (ANT). Twenty-six naturally cycling, healthy women were tested thrice: during menses, in the follicular phase, and in the luteal phase. In the emotional face flanker task, a significant positive relation was found between progesterone levels and reaction times (RTs) for sad faces, suggesting that high progesterone levels may activate the social monitoring system and allocate more attention to the social stimulus, which benefits individuals' survival and adaptation. In the ANT, a significant increase was found in RTs and accuracy during the luteal phase, suggesting that luteal women increase this accuracy by exerting a relatively conservative strategy of allocating more attention to the targets. Taken together, these findings indicate that high levels of progesterone may facilitate social information processing by optimizing attention allocation. Moreover, overactivation of the social monitoring system may make women more susceptible to stressors and promote affective disturbances, which may provide underlying pathophysiology of the premenstrual dysphoric disorder.


Assuntos
Estradiol/metabolismo , Reconhecimento Facial/fisiologia , Progesterona/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia , Emoções/fisiologia , Estradiol/fisiologia , Feminino , Fase Folicular/fisiologia , Humanos , Fase Luteal/fisiologia , Ciclo Menstrual/fisiologia , Progesterona/fisiologia , Tempo de Reação/efeitos dos fármacos , Comportamento Social , Adulto Jovem
20.
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
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