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1.
J Ovarian Res ; 12(1): 86, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526389

RESUMO

AIMS: This study was designed to evaluate the protective effects of AMPKα and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms. METHODS: An in vitro PCOS model was established by DHEA (6 mg/(100 g•d)), and the rats were randomly divided into the metformin group (MF group, n = 11), the exenatide group (EX group, n = 11), the PCOS group (n = 10), and the normal control group (NC group, n = 10). The MF group was administered MF 300 mg/(kg•d) daily. The EX group was subcutaneously injected EX 10µg/(kg•d) daily. After 4 weeks of continuous administration, fasting blood glucose and serum androgen, luteinizing hormone and other biochemical indicators were measured. Western and Real-time PCR were used to determine the expression of AMPKα and SIRT1 in the ovaries of each group. RESULTS: After 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 ± 16.57, 218.63 ± 13.18 vs 238.30 ± 12.26 g, P = 0.026), fasting blood glucose (7.71 ± 0.72, 8.17 ± 0.54 vs 8.68 ± 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 ± 2.50, 7.44 ± 1.23 vs 12.66 ± 1.44, P < 0.01) and serum androgen (0.09 ± 0.03, 0.09 ± 0.03 vs 0.53 ± 0.41 ng/ml, P < 0.01) and the expressions of AMPKα and SIRT11 were increased progressively (P < 0.05). CONCLUSIONS: Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Exenatida/farmacologia , Metformina/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Sirtuína 1/genética , Androgênios/sangue , Animais , Glicemia/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Resistência à Insulina/genética , Hormônio Luteinizante/genética , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/genética , Ratos
2.
BMC Res Notes ; 12(1): 455, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340838

RESUMO

OBJECTIVE: Study analyzes mutation in mtDNA (Mitochondrial DNA) among diabetic women with PCOS in non-diabetic diabetic women and compared with the healthy control. Women with known case of hyperandrogenism, ovulatory dysfunction and/or polycystic ovaries were selected and anthropometric and demographic variables were collected during their clinical visit. Biochemical estimation of glucose, FSH, LH, estradiol (E2), and insulin levels were analyzed. Mutational analysis of mt-tRNA genes of each individual was compared with the updated consensus Cambridge sequence. The mtDNA content was determined in triplicate using SYBR green PCR mastermix. RESULTS: The clinical and biochemical characteristics of participants showed no statistical difference in age and/or FSH, PRL, E2, PRGE or fasting glucose value between patients of different groups. Women with PCOS-D had significantly higher LH, LH/FSH, TT and fasting insulin levels and HOMA-IR with respect to the control group. Ten different type of mutation were seen in POCS group. Most of these mutations were confined to evolutionarily conserved region. The mtDNA copy numbers were considerably lower PCOS group irrespective of diabetic status. To conclude, the current study inferred that the mutations occur in the mitochondrial genome, mt-tRNA in specific, are the important causal factor in PCOS.


Assuntos
DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/genética , Hiperandrogenismo/genética , Mitocôndrias/genética , Síndrome do Ovário Policístico/genética , RNA de Transferência/genética , Adulto , Glicemia/metabolismo , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , DNA Mitocondrial/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/genética , Expressão Gênica , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/complicações , Hiperandrogenismo/patologia , Insulina/sangue , Resistência à Insulina , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Herança Materna , Mitocôndrias/patologia , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/patologia , Estudos Prospectivos , RNA de Transferência/sangue
3.
Syst Biol Reprod Med ; 65(5): 400-408, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30958034

RESUMO

Altered folliculogenesis and reproductive anomalies in polycystic ovary syndrome (PCOS) suggest that variations of genes involved in folliculogenesis might influence etiopathogenesis of this syndrome. The objective of this study was to assess the association of LHß (rs1056917) and lutropin receptor (LHR) (rs61996318) polymorphism with polycystic ovarian syndrome and to interrelate the levels of luteinizing hormone (LH) with severity of clinical manifestations of PCOS. Three hundred women of reproductive age were enrolled in this retrospective case-control study. Rotterdam Criteria was used to diagnose PCOS patients. Nucleotide mutations of LH and LHR gene was analyzed using polymerase chain reaction-restriction fragment length polymorphism. High LH levels were found in 88% of PCOS patients. LHß TC and CC genotypes were significantly associated with PCOS risk (OR [odds ratio] 13.95, CI [confidence interval] 6.30-30.86, p < 0.0001 and OR 3.31, CI 1.30-8.41, p = 0.01). The frequency of the C allele was 0.31 in PCOS and 0.02 in controls (OR 18.80, CI 8.54-41.37, p < 0.0001). LHR CA and AA genotype conferred a significant risk in development of PCOS (OR 5.07, CI 2.50-10.31, p < 0.0001). The frequency of the A allele was 0.51 in PCOS and 0.03 in controls (OR 26.62, CI 13.99-50.65, p < 0.0001). The results show an association between polymorphism of LHß, LHR and PCOS, indicating that variants of these genes may affect the metabolic pathways involved in this syndrome. Majority of the affected women were found to have elevated LH levels. This study sheds new light in the diagnosis, treatment and management of PCOS syndrome. Abbreviations: AUC: area under curve; BMI: body mass index; C: cholesterol; CI: confidence interval; DBP: diastolic blood pressure; DHEAS: dehydroepiandrosterone sulfate; FG: Ferriman-Gallway; FSH: follicle stimulating hormone; GHQ: general health questionnaire; HA: hyperandrogenism; HDL-C: high-density lipoprotein cholesterol; HOMA-IR: homeostatic model assessment for insulin resistance; HWR: hip waist ratio; LDL-C: low-density lipoprotein cholesterol; LH: luteinizing hormone; LH: luteinizing hormone; LHR: lutropin receptor; O: oligomenorrhea; OR: odds ratio; PCO: polycystic ovaries; PCO: polycystic ovary; PCOS: polycystic ovary syndrome; PCR: polymerase chain reaction; ROC: receiver operating curve; SBP: systolic blood pressure; SE: standard error of coefficient; SNP: single nucleotide polymorphism; TG: triglycerides; TSH: thyroid stimulating hormone; VD: vitamin D.


Assuntos
Hormônio Luteinizante/genética , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Receptores do LH/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Índia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
4.
Reprod Biol Endocrinol ; 17(1): 18, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728019

RESUMO

OBJECTIVE: To study the role of recombinant human LH supplementation in women with hypo-response to ovarian stimulation. METHODS: We performed a systematic review and meta-analysis of prospective clinical trials in which recombinant FSH monotherapy protocols were compared with LH-supplemented protocols in hypo-responders. A search was conducted of the Scopus, MEDLINE databases without time or language restrictions. Primary outcome was clinical pregnancy rate. RESULTS: Significantly higher clinical pregnancy rates (odds ratio: 2.03, P = 0.003), implantation rates (odds ratio: 2.62, P = 0.004) and number of oocytes retrieved (weight mean differences: 1.98, P = 0.03) were observed in hypo-responders supplemented with recombinant LH versus hypo-responders who underwent FSH monotherapy. No differences in terms of mature oocytes or miscarriage rates were found between the two groups. CONCLUSION: In conclusion, our analysis confirms that women with a hypo-response to exogenous gonadotropins might benefit from LH supplementation. However, more trials are required before a definitive conclusion can be drawn.


Assuntos
Hormônio Foliculoestimulante/uso terapêutico , Gonadotropinas/uso terapêutico , Hormônio Luteinizante/uso terapêutico , Indução da Ovulação/métodos , Proteínas Recombinantes/uso terapêutico , Ensaios Clínicos como Assunto , Implantação do Embrião/efeitos dos fármacos , Feminino , Humanos , Hormônio Luteinizante/genética , Gravidez , Taxa de Gravidez , Estudos Prospectivos
5.
Prog Mol Biol Transl Sci ; 161: 69-89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30711030

RESUMO

Accumulating evidence showed that the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is an essential regulator of sexual development and reproduction from zebrafish to human. Activating and inactivating mutations of LHCGR gene have been identified from patients of different phenotypes. Familial male-limited precocious puberty, Leydig cell hypoplasia, and empty follicle syndrome are caused by LHCGR mutations. More than 50 mutations have been reported from subjects of different ethnic backgrounds. Functional analyses of the mutant LHCGR revealed multiple defects, including cell surface expression, ligand binding, and signaling. The difference of the two native ligands and signaling pathway activated by LHCGR are illustrated. Potential therapeutic implications from the analyses of the naturally occurring LHCGR mutations, such as pharmacological chaperones, are highlighted.


Assuntos
Doença/genética , Hormônio Luteinizante/genética , Mutação/genética , Receptores do LH/genética , Sequência de Aminoácidos , Sequência de Bases , Humanos , Receptores do LH/química , Transdução de Sinais
6.
Endocrinology ; 160(1): 57-67, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30517625

RESUMO

The hypothalamic decapeptide, GnRH, is the gatekeeper of mammalian reproductive development and function. Activation of specific, high-affinity cell surface receptors (GnRH receptors) on gonadotropes by GnRH triggers signal transduction cascades to stimulate the coordinated synthesis and secretion of the pituitary gonadotropins FSH and LH. These hormones direct gonadal steroidogenesis and gametogenesis, making their tightly regulated production and secretion essential for normal sexual maturation and reproductive health. FSH and LH are glycoprotein heterodimers comprised of a common α-subunit and a unique ß-subunit (FSHß and LHß, respectively), which determines the biological specificity of the gonadotropins. The unique ß-subunit is the rate-limiting step for the production of the mature gonadotropins. Therefore, FSH synthesis is regulated at the transcriptional level by Fshb gene expression. The overarching goal of this review is to expand our understanding of the mechanisms and pathways underlying the carefully orchestrated control of FSH synthesis and secretion by GnRH, focusing on the transcriptional regulation of the Fshb gene. Identification of these regulatory mechanisms is not only fundamental to our understanding of normal reproductive function but will also provide a context for the elucidation of the pathophysiology of reproductive disorders and infertility to lead to potential new therapeutic approaches.


Assuntos
Subunidade beta do Hormônio Folículoestimulante/genética , Hormônio Liberador de Gonadotropina/metabolismo , Animais , Feminino , Subunidade beta do Hormônio Folículoestimulante/metabolismo , Regulação da Expressão Gênica , Hormônio Liberador de Gonadotropina/genética , Humanos , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo
7.
Biosci Rep ; 39(1)2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30463907

RESUMO

Large doses of flavonoids could cure many diseases with no serious side effects. However, the role of flavonoids in the treatment of polycystic ovary syndrome (PCOS) has not been reported. Therefore, total flavonoids extracted from Nervilia Fordii were selected to explore its therapeutic efficiency in PCOS. PCOS rat model was constructed to explore the role of total flavonoids in the treatment of PCOS. ELISA was used to assess the changes of ovulation function under the treatment of total flavonoids with or without exogenous interleukin-6 (IL-6). Western blot, real-time PCR and immunohistochemistry were carried out to assess the related molecular mechanisms. We explored that total flavonoids obviously increased the serum levels of follicle-stimulating hormone (FSH), and sharply decreased the serum levels of luteinizing hormone (LH), testosterone (T) and insulin (INS) in the PCOS-IR rats via partly inhibiting the activation of JAK2/STAT3 pathway, partially up-regulating the IL-6 expression and partially down-regulating the suppressor of cytokine signaling 3 (SOCS3) expression in ovaries of PCOS rats. The effect of total flavonoids on estrous cycles, serum levels of FSH, LH, T and INS were partially attenuated by IL-6 in PCOS rat model. Moreover, IL-6 significantly reversed the effect of total flavonoids on the phosphorylation of JAK2/STAT3, the expression of IL-6 and SOCS3 in ovaries of PCOS rats. Total flavonoids extracted from Nervilia Fordii might induce the expression of IL-6 in ovary and act as a potential therapeutic drug for the treatment of PCOS.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonoides/farmacologia , Interleucina-6/genética , Janus Quinase 2/genética , Orchidaceae/química , Síndrome do Ovário Policístico/tratamento farmacológico , Fator de Transcrição STAT3/genética , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Glicemia , Gonadotropina Coriônica/administração & dosagem , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Feminino , Flavonoides/isolamento & purificação , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Insulina/administração & dosagem , Insulina/sangue , Resistência à Insulina , Interleucina-6/sangue , Interleucina-6/farmacologia , Janus Quinase 2/sangue , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Ovulação/efeitos dos fármacos , Extratos Vegetais/química , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/sangue , Transdução de Sinais , Testosterona/sangue , Testosterona/genética
8.
Genet Test Mol Biomarkers ; 23(1): 39-44, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30585745

RESUMO

BACKGROUND: Follicle-stimulating hormone (FSH) is essential to the hypothalamic-pituitary-gonadal axis, playing a key role in human reproduction. It is a heterodimer comprised of a hormone-specific ß-chain (FSH-ß) that is associated with an α-chain. It exerts its biological activities by binding to the FSH receptor (FSHR). The ß-subunit, which is encoded by the FSHB gene, is responsible for ensuring binding specificity to the FSHR. There is a promoter polymorphism in this gene, c.-211G>T (rs10835638), upstream of the transcription start site; and in vitro studies have reported that the T allele decreases FSHB transcription in gonadotrophic cells. AIMS: Investigate the possible effects of the FSHB c.-211G/T polymorphism on hormonal profile and in in vitro fertilization (IVF)/intracytoplasmic sperm injection outcomes in normoovulatory Brazilian women. METHODS: A cross-sectional study of 140 women (median age = 33 years [CI: 32-34]) with infertility mainly caused by male (n = 85) or tuboperitoneal (n = 55) factors. In this study we evaluated FSH, estradiol, luteinizing hormone (LH), progesterone, prolactin and anti-Mullerian hormone levels, and antral follicle counting (AFC). Genotyping was performed using the TaqMan real-time polymerase chain reaction methodology. RESULTS: The wild-type allele G was found in 86.4% and the polymorphic allele T in 13.6% of the women respectively. The TT genotype was not found in any women. Women carrying the GT genotype had a poorer response more frequently to controlled ovarian hyperstimulation when compared to individuals with the GG genotype (47.4% vs. 26.5%, p = 0.010), higher LH levels (3.1 IU/mL vs. 2.4 IU/mL, p = <0.001), lower AFC (8.0 vs. 10.0, p = 0.03), oocytes retrieved (3.0 vs. 5.0, p = 0.03), MII (3.0 vs. 4.0, p = 0.02), and embryos (2.0 vs. 3.0, p = 0.02). Despite these findings, no difference was observed in pregnancy rate. CONCLUSION: Our findings suggest that the FSHB c.-211G/T polymorphism may modestly alter some aspects of the female reproductive system, but they are not associated with significantly different IVF outcomes.


Assuntos
Proteínas de Transporte/genética , Glicopeptídeos/genética , Adulto , Alelos , Hormônio Antimülleriano/genética , Brasil , Estudos Transversais , Feminino , Fertilização In Vitro , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Subunidade beta do Hormônio Folículoestimulante/genética , Frequência do Gene/genética , Genótipo , Humanos , Hormônio Luteinizante/genética , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Taxa de Gravidez , Regiões Promotoras Genéticas/genética , Receptores do FSH , Saúde Reprodutiva
9.
Elife ; 72018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30565563

RESUMO

Neurokinin B (NKB) signaling is critical for reproduction in all studied species. The existing consensus is that NKB induces GnRH release via kisspeptin (Kiss1) stimulation in the arcuate nucleus. However, the stimulatory action of NKB is dependent on circulating estrogen (E2) levels, without which, NKB inhibits luteinizing hormone (LH) release. Importantly, the evidence supporting the kisspeptin-dependent role of NKB, derives from models of persistent hypogonadal state [e.g. Kiss1r knock-out (KO) mice], with reduced E2 levels. Here, we demonstrate that in the presence of E2, NKB signaling induces LH release in a kisspeptin-independent manner through the activation of NK3R (NKB receptor) neurons in the posterodorsal medial amygdala (MePD). Importantly, we show that chemogenetic activation of MePD Kiss1 neurons induces LH release, however, the stimulatory action of NKB in this area is Kiss1 neuron-independent. These results document the existence of two independent neuronal circuitries within the MePD that regulate reproductive function in females. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).


Assuntos
Estrogênios/metabolismo , Kisspeptinas/genética , Neurocinina B/genética , Receptores de Taquicininas/genética , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Complexo Nuclear Corticomedial , Estrogênios/genética , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Luteinizante/antagonistas & inibidores , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Camundongos , Camundongos Knockout , Neurocinina B/metabolismo , Neurônios/metabolismo , Transdução de Sinais
10.
J Biosci ; 43(4): 569-574, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30207304

RESUMO

The essential role of regular physical activity has been emphasized for maintaining a healthy life. However, unfortunately, during the last few decades, the lifestyle of people has led to a decrease in physical activity. Research studies have shown that exercise of different intensities is applied on reproductive performance indices, luteinizing hormone (LH) and testosterone (T), with different effects. Nevertheless, the molecular and cellular mechanisms underlying its function are not completely understood. Therefore, this study aimed to evaluate the role of kisspeptin, neurokinin-B and pro-dynorphin (KNDY) gene-expression changes located in the upstream of GnRH neurons in transferring the effects of different long-term exercise intensities on male reproductive axis. Twenty-one adult Wistar rats were randomly divided into control, 6-month regular moderate exercise (RME-6) and 6-month regular intensive exercise (RIE-6). In moderate and intensive exercise groups, rats were treated 5 days a week for 60 min, at 22 and 35 m/min, respectively. Finally, the hypothalamic arcuate nucleus was isolated and the relative gene expression of kisspeptin (Kiss1), neurokinin-B (Nkb), pro-dynorphin (Pdyn) and gonadotropin-releasing hormone (Gnrh) genes were measured by realtime polymerase chain reaction method. The results showed that RIE-6 treatment decreased Gnrh and increased Pdyn mRNA levels in the arcuate nucleus. Furthermore, although RME-6 treatment decreased Nkb and increased Pdyn mRNA levels, the Gnrh mRNAwas not affected. Regarding the Gnrh mRNA levels and serum concentrations of reproductive indices (LH and T), moderate exercise did not impose harmful effects on the hypothalamic-pituitary-gonadal axis than intensive exercise. The different impacts of diverse long-term exercise intensities on the male pituitary-gonadal axis maybe relay by the various changes in hypothalamic Nkb and Pdyn gene expressions.


Assuntos
Encefalinas/genética , Gônadas/metabolismo , Neurocinina B/genética , Condicionamento Físico Animal/fisiologia , Hipófise/metabolismo , Precursores de Proteínas/genética , Animais , Regulação da Expressão Gênica/genética , Hormônio Liberador de Gonadotropina/genética , Gônadas/fisiologia , Humanos , Kisspeptinas/genética , Hormônio Luteinizante/genética , Masculino , Neurônios/metabolismo , Hipófise/fisiologia , RNA Mensageiro/genética , Ratos , Ratos Wistar , Testosterona/genética , Testosterona/metabolismo
11.
Gen Comp Endocrinol ; 269: 149-155, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30236970

RESUMO

In Seriola species, exposure to a long photoperiod regime is known to induce ovarian development. This study examined photoperiodic effects on pituitary gene expression and plasma levels of follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) in previtellogenic greater amberjack (Seriola dumerili). The fish were exposed to short (8L:16D) or long (18L:6D) photoperiod. The water temperature was maintained at 22 °C. Compared with the short-photoperiod group, plasma Fsh levels were higher on days 10 and 30 in the long-photoperiod group, but plasma Lh levels did not significantly differ. On day 30, pituitary Fsh- and Lh-ß subunit gene expressions were also higher in the long-photoperiod group than the short-photoperiod group, whereas α-subunit gene expressions were higher on days 20 and 30. Throughout the experiment, average gonadosomatic index and plasma E2 levels did not significantly differ between the two groups. This study clearly demonstrated that a long photoperiod induced Fsh release in the previtellogenic fish followed by upregulation of pituitary Fsh and Lh subunit gene expressions. An increase in plasma Fsh levels may be a key factor that mediates the photoperiodic effect on the initiation of ovarian development.


Assuntos
Gonadotropinas/sangue , Perciformes/sangue , Perciformes/fisiologia , Fotoperíodo , Vitelogênese , Animais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Subunidade alfa de Hormônios Glicoproteicos/genética , Subunidade alfa de Hormônios Glicoproteicos/metabolismo , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Hormônio Luteinizante Subunidade beta/genética , Hormônio Luteinizante Subunidade beta/metabolismo , Ovário/crescimento & desenvolvimento , Perciformes/crescimento & desenvolvimento , Perciformes/metabolismo , Hipófise/citologia , Hipófise/metabolismo , Temperatura , Água
12.
Minerva Ginecol ; 70(5): 561-587, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30264954

RESUMO

This review article centers upon family of gonadotropin hormones which consists of two pituitary hormones - follicle-stimulating hormone (FSH) and luteinizing hormone (LH) as well as one non-pituitary hormone - human chorionic gonadotropin (hCG) secreted by placenta, and their receptors. Gonadotropins play an essential role in proper sexual development, puberty, gametogenesis, maintenance of pregnancy and male sexual differentiation during the fetal development. They belong to the family of glycoprotein hormones thus they constitute heterodimeric proteins built of common α subunit and hormone-specific ß-subunit. Hitherto, several mutations in genes encoding both gonadotropins and their receptors have been identified in humans. Their occurrence resulted in a number of different phenotypes including delayed puberty, primary amenorrhea, hermaphroditism, infertility and hypogonadism. In order to understand the effects of mutations on the phenotype observed in affected patients, detailed molecular studies are required to map the relationship between the structure and function of gonadotropins and their receptors. Nonetheless, in vitro assays are often insufficient to understand physiology. Therefore, several animal models have been developed to unravel the physiological roles of gonadotropins and their receptors.


Assuntos
Gonadotropina Coriônica/fisiologia , Hormônio Foliculoestimulante/fisiologia , Hormônio Luteinizante/fisiologia , Animais , Gonadotropina Coriônica/genética , Feminino , Doenças Urogenitais Femininas/genética , Doenças Urogenitais Femininas/fisiopatologia , Hormônio Foliculoestimulante/genética , Humanos , Hormônio Luteinizante/genética , Masculino , Doenças Urogenitais Masculinas/genética , Doenças Urogenitais Masculinas/fisiopatologia , Modelos Animais , Mutação , Fenótipo , Gravidez , Receptores da Gonadotropina/genética , Receptores da Gonadotropina/fisiologia
13.
Int J Dev Neurosci ; 71: 163-171, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30130567

RESUMO

PURPOSE: It is known that various types of stress in early life increase the incidence of diabetes, myocardial infarctions, and psychiatric disorders in adulthood. We examined the mechanism by which neonatal immune stress reduces sexual behavior in adult male rats. METHODS: Male rats were randomly divided into 3 groups: the control (n = 17), postnatal day 10 lipopolysaccharide (PND10LPS) (n = 31), and PND25LPS (n = 16) groups, which received intraperitoneal injections of LPS (100 µg/kg) or saline (injection volume: ≤0.1 ml/g) on postnatal days 10 and 25. In experiment 1, male rats (age: 11 to 12 weeks) were put together with female rats in a one-to-one setting for mating, and sexual behavior (mounting, intromission, and ejaculation) was monitored for 30 minutes. The serum levels of luteinizing hormone (LH) and testosterone (T) and the hypothalamic mRNA expression levels of factors related to sexual behavior were examined. After experiment 1 finished, the remaining 37 male rats were used for experiment 2: the control group (n = 8), PND10 LPS group (n = 21) and PND25LPS group (n = 8) these rats had been given an i.p. injection of the saline during the expriment1. All of the rats were orchidectomized at 14 weeks of age. After a 3-week recovery period, a silastic tube containing crystalline T was subcutaneously implanted into the back of each rat. The rats' sexual behavior, serum hormone concentrations, and hypothalamic mRNA expression levels were assessed. RESULTS: In experiment 1, preputial separation occurred significantly later in the PND10LPS group than in the control group. The frequency of sexual behavior was significantly lower in the PND10LPS group than in the control group. The serum T concentrations of the PND10LPS and PND25LPS groups were significantly lower than that of the control group, but the serum LH concentrations of the 3 groups did not differ significantly. The hypothalamic mRNA expression levels of progesterone receptor B (PRB) and gonadotropin-releasing hormone (GnRH) were significantly lower in the PND10LPS and PND25LPS groups than in the control group, whereas the hypothalamic PRA + B mRNA expression levels of the 3 groups did not differ significantly. In experiment 2, after T supplementation the frequency of sexual behavior was significantly lower in the PND10LPS and PND25LPS groups than in the control group, although there were no significant differences in the serum T or LH concentrations or the hypothalamic PRB, PRA + B, or GnRH mRNA expression levels of the 3 groups. CONCLUSION: In male rats, immune stress in the early neonatal period delayed sexual maturation, reduced sexual behavior, suppressed the serum T concentration, and downregulated the hypothalamic mRNA expression levels of GnRH and the PR in adulthood. The delayed sexual maturation was presumed to have been caused by the reduction in the serum T concentration. However, the rats that experienced neonatal stress exhibited reduced sexual behavior irrespective of their serum T concentrations.


Assuntos
Androgênios/metabolismo , Transtornos do Desenvolvimento Sexual/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Receptores de Progesterona/metabolismo , Estresse Psicológico/metabolismo , Fatores Etários , Androgênios/genética , Animais , Animais Recém-Nascidos , Transtornos do Desenvolvimento Sexual/induzido quimicamente , Transtornos do Desenvolvimento Sexual/patologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Lipopolissacarídeos/farmacologia , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Masculino , RNA Mensageiro/metabolismo , Ratos , Receptores de Progesterona/genética , Estresse Psicológico/patologia , Testosterona/sangue , Testosterona/genética
14.
J Assist Reprod Genet ; 35(9): 1703-1712, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29974367

RESUMO

PURPOSE: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) mediate intracellular functions by binding their specific protein G-coupled gonadotrophin receptor, respectively FSH receptor (FSHR) and LH/choriogonadotrophin receptor (LHCGR). Whereas the expression of FSHR and LHCGR in mammals was considered gonad-specific and cell-specific, studies identified gonadotrophin receptors in human female extragonadal reproductive tissues. This study aims to demonstrate that gonadotrophin receptors are expressed in endometrium and mediates intracellular functions. METHODS: Collected endometria (n = 12) from healthy patients (mean age of 36 ± 6) were primary cultured for 24 h. The presence of gonadotrophin receptors was evaluated by RT-PCR followed by the sequencing of the resulted amplicons and by immunohistochemistry in original samples. Endometrial primary cultures were treated with increasing concentration (range 0-100 ng/ml) of either recombinant human LH (rhLH) or recombinant human FSH (rhFSH). Endometria controls had gonadotrophin replaced by the same volume of the culture medium. In gonadotrophin-treated samples, it was evaluated the intracellular cyclic adenosine monophosphate (cAMP) content by enzymatic immunoassay and the expression of steroidogenic genes by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). RESULTS: The sequencing of the RT-PCR amplicons confirmed the presence of both gonadotrophin receptors and immunohistochemistry localized them on the membrane of endometrial glands cells throughout the glandular epithelium. The gonadotrophin-receptor complex was able to increase the intracellular cAMP in a dose-response and time-course manner and to induce steroidogenic genes expression. CONCLUSION: This study demonstrates that both gonadotrophin receptors are expressed along the glandular epithelium of endometria and they mediate the effects of gonadotrophins on intracellular functions.


Assuntos
Endométrio/metabolismo , Receptores do FSH/genética , Receptores do LH/genética , Adulto , Gonadotropina Coriônica/genética , AMP Cíclico/metabolismo , Endométrio/crescimento & desenvolvimento , Feminino , Hormônio Foliculoestimulante/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Gravidez , Receptores do FSH/metabolismo , Transdução de Sinais/genética
15.
EMBO J ; 37(17)2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-30037826

RESUMO

The number and self-renewal capacity of hematopoietic stem cells (HSCs) are tightly regulated at different developmental stages. Many pathways have been implicated in regulating HSC development in cell autonomous manners; however, it remains unclear how HSCs sense and integrate developmental cues. In this study, we identified an extrinsic mechanism by which HSC number and functions are regulated during mouse puberty. We found that the HSC number in postnatal bone marrow reached homeostasis at 4 weeks after birth. Luteinizing hormone, but not downstream sex hormones, was involved in regulating HSC homeostasis during this period. Expression of luteinizing hormone receptor (Lhcgr) is highly restricted in HSCs and multipotent progenitor cells in the hematopoietic hierarchy. When Lhcgr was deleted, HSCs continued to expand even after 4 weeks after birth, leading to abnormally elevated hematopoiesis and leukocytosis. In a murine acute myeloid leukemia model, leukemia development was significantly accelerated upon Lhcgr deletion. Together, our work reveals an extrinsic counting mechanism that restricts HSC expansion during development and is physiologically important for maintaining normal hematopoiesis and inhibiting leukemogenesis.


Assuntos
Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Hormônio Luteinizante/metabolismo , Receptores do LH/metabolismo , Maturidade Sexual , Transdução de Sinais , Animais , Células-Tronco Hematopoéticas/patologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Hormônio Luteinizante/genética , Camundongos , Camundongos Knockout , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Receptores do LH/genética
16.
Genet Test Mol Biomarkers ; 22(7): 405-412, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29957069

RESUMO

AIMS: This is a follow-up study based on the results of our previous article, to further explore the effect of the TP53 codon 72 (rs1042522) and MDM2 SNP309 (rs2279744) polymorphisms on basal follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratios in infertility women. MATERIALS AND METHODS: The distribution of two genetic polymorphisms (rs1042522 and rs2279744) and basal FSH/LH ratios were tested and analyzed in 1051 in vitro fertilization (IVF) patients at a university-affiliated hospital. RESULTS: The TP53 codon 72 polymorphism had a significant association with the FSH/LH ratio (group I: FSH/LH <2.3 and group II: FSH/LH ≥2.3) (C/C vs. G/G: odds ratio [OR] = 1.69, 95% confidence interval [CI]: 1.07-2.65, p = 0.02; G/C vs. G/G: OR = 1.86, 95% CI: 1.25-2.77, p = 0.002). In a stratification analysis, C allele carriers and the C/C genotype showed a strong association with positive clinical pregnancy outcomes after IVF compared with G allele carriers and the G/G genotype in the recessive, dominant, and allelic genetic models in group I (C/C vs. G/G: OR = 1.84, 95% CI: 1.25-2.69, p = 0.01; C/C vs. G carrier: OR = 1.52, 95% CI: 1.12-2.07, p = 0.01; C carrier vs. G/G: OR = 1.46, 95% CI: 1.07-2.01, p = 0.02; C allele vs. G allele: OR = 1.34, 95% CI: 1.11-1.62, p = 0.003), no significant associations by stratification were observed for group II. No associations were found between MDM2 SNP309 and either of two groups. CONCLUSION: The TP53 codon 72 polymorphism is associated with FSH/LH ratios, suggesting that it is a potential predictive genetic marker of IVF outcome in patients younger than 35 years of age with baseline FSH levels below 10 IU/L and who have an FSH/LH ratio <2.3.


Assuntos
Hormônio Foliculoestimulante/metabolismo , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismo , Hormônio Luteinizante/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores/análise , China , Códon , Feminino , Hormônio Foliculoestimulante/genética , Seguimentos , Frequência do Gene , Genótipo , Humanos , Hormônio Luteinizante/genética , Indução da Ovulação , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo
17.
Hum Reprod Update ; 24(5): 599-614, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29924306

RESUMO

BACKGROUND: Genotype has been implicated in the outcome of ovarian stimulation. The analysis of patient-specific genotypes might lead to an individualized pharmacogenomic approach to controlled ovarian stimulation (COS). However, the validity of such an approach remains to be established. OBJECTIVE AND RATIONALE: To define the impact of specific genotype profiles of follicle-stimulating hormone, luteinizing hormone and their receptors (FSHR, LHR and LHCGR) on ovarian stimulation outcome. Specifically, our aim was to identify polymorphisms that could be useful in clinical practice, and those that need further clinical investigation. SEARCH METHODS: A systematic review followed by a meta-analysis was performed according to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines without time restriction. We searched the PubMed/MEDLINE, Cochrane Library, SCOPUS and EMBASE databases to identify all relevant studies published before January 2017. Only clinical trials published as full-text articles in peer-reviewed journals were included. The primary outcome was the number of oocytes retrieved. OUTCOMES: Fifty-seven studies were assessed for eligibility, 33 of which were included in the qualitative and quantitative analyses. Data were independently extracted using quality indicators. COS outcomes related to seven polymorphisms (FSHR [rs6165], FSHR [rs6166], FSHR [rs1394205], LHB [rs1800447], LHB [rs1056917], LHCGR [rs2293275] and LHCGR [rs13405728]) were evaluated. More oocytes were retrieved from FSHR (rs6165) AA homozygotes (five studies, 677 patients, weighted mean difference [WMD]: 1.85, 95% CI: 0.85-2.85, P < 0.001; I2 = 0%) than from GG homozygotes and AG heterozygotes (four studies, 630 patients, WMD: 1.62, 95% CI: 0.28-2.95, P = 0.020; I2 = 56%). Moreover, stimulation duration was shorter in FSHR (rs6165) AA homozygotes than in AG carriers (three studies, 588 patients, WMD -0.48, 95% CI: -0.87 to -0.10, P = 0.010, I2 = 44%). A higher number of oocytes (21 studies, 2632 patients WMD: 0.84, 95% CI: 0.19 to 1.49, P = 0.01, I2 = 76%) and metaphase II oocytes (five studies, 608 patients, WMD: 1.03, 95% CI: 0.01-2.05, P = 0.050, I2 = 0%) was observed in AA than in GG homozygote carriers. FSH consumption was significantly lower in FSHR (rs1394205) GG homozygotes (three studies, 411 patients, WMD: -1294.61 IU, 95% CI: -593.08 to -1996.14 IU, P = 0.0003, I2 = 99%) and AG heterozygotes (three studies, 367 patients, WMD: -1014.36 IU, 95% CI: -364.11 to -1664.61 IU, P = 0.002, I2 = 99%) than in AA homozygotes. WIDER IMPLICATIONS: These results support the clinical relevance of specific genotype profiles on reproductive outcome. Further studies are required to determine their application in a pharmacogenomic approach to ovarian stimulation.


Assuntos
Gonadotropinas/genética , Indução da Ovulação , Variantes Farmacogenômicos , Feminino , Hormônio Foliculoestimulante/genética , Genótipo , Humanos , Hormônio Luteinizante/genética , Receptores do FSH/genética , Receptores do LH/genética
18.
DNA Cell Biol ; 37(7): 600-608, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29746152

RESUMO

Over the past decades, an increase has been described in exposure to environmental toxins; consequently, a series of studies has been carried out with the aim of identifying problems associated with health. One of the main risk factors is exposure to heavy metals. The adverse effects that these compounds exert on health are quite complex and difficult to elucidate, in that they act at different levels and there are various signaling pathways that are implicated in the mechanisms of damage. The Sertoli cells plays a role of vital importance during the process of spermatogenesis, and it has been identified as one of the principal targets of heavy metals. In the present review, cadmium, lead, and arsenic are broached as altering the physiology of the Sertoli cells, citing mechanisms that have been cited in the literature.


Assuntos
Arsênico/toxicidade , Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Chumbo/toxicidade , Células de Sertoli/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Humanos , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Masculino , Células de Sertoli/citologia , Células de Sertoli/metabolismo , Transdução de Sinais , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Testosterona/antagonistas & inibidores , Testosterona/genética , Testosterona/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Gene ; 664: 181-191, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-29704632

RESUMO

Seasonal estrus is a critical limiting factor for animal fecundity. However, estrus occurs in some seasonally estrous sheep in the non-breeding season, and this phenomenon involves changes in ovarian biology. Previous studies indicated that small RNAs, such as microRNAs (miRNAs), play important regulatory roles in ovarian biology. Differentially expressed miRNAs in the ovaries of estrous sheep were identified using Solexa sequencing technology. A total of 423 known miRNAs were identified in ovaries of estrous sheep in the breeding season and non-breeding season. In the comparison of these two groups, 48 miRNAs were identified that were differentially expressed between the two groups (including 5 up-regulated and 43 down-regulated miRNAs). KEGG pathway analysis revealed that the target genes of some differentially expressed miRNAs were involved in pathways related to reproductive hormone signaling and follicular development. Furthermore, the levels of estradiol (E2), progesterone (P4), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were lower in anestrus sheep than in sheep during the breeding season. Upon combining the pathway enrichment analysis, target gene expression and hormone measurement results, we suggest that these differentially expressed miRNAs might influence ovarian activity in the non-breeding season by regulating the above pathways. The identification of miRNAs that are differentially expressed between ovines in the breeding season and non-breeding season will contribute to our understanding of the role of miRNAs in estrus regulation, and these data may provide a basis for regulating estrus in sheep during the non-breeding season.


Assuntos
Cruzamento , Estro/genética , Perfilação da Expressão Gênica/veterinária , MicroRNAs/metabolismo , Ovário/metabolismo , Ovinos/fisiologia , Animais , Regulação para Baixo , Estradiol/genética , Estradiol/metabolismo , Estro/metabolismo , Feminino , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , MicroRNAs/genética , Progesterona/metabolismo , Regulação para Cima
20.
Georgian Med News ; (Issue): 34-40, 2018 Feb.
Artigo em Russo | MEDLINE | ID: mdl-29578420

RESUMO

PCOS has a leading place in women's infertility. Based on the data of recent researches, Anti-Mullerian hormone (AMH) has been considered as one of the diagnostic criteria for PCOS. The aim of study was to determine the correlation of Anti-Mullerian hormone with hormonal and ovarian morphological characteristics in patients with PCOS, with and without insulin resistance. 110 women with diagnosis of PCOS were involved in the study. Patients were divided into two groups: PCOS patients with insulin resistance (60 women) and PCOS patients without insulin resistance (50 women). All patients underwent hormonal investigation (AMH, FSH, LH, T, FT, HOMA- IR, FAI and SHBG). The volume of ovaries and the number of antral follicles (AFC) were determined by ultrasound imaging. Сorrelation between AMH and the ovarian hormonal and morphological characteristics has been shown. In particular, a significant positive correlation between AMH and the volume of the ovaries in both groups was demonstrated. In the group of patients with PCOS and insulin resistance a positive correlation between AMH and the volum of ovary, AFC was shown, as well as a negative correlation between AMH and SHBG. In the same group a tendency of the positive correlation between AMH and TT, HOMA-IR and IRI was seen. In the group of patients with PCOS without insulin resistence a positive correlation between AMH and the volum of ovary was observed, as well as the tendency of positive correlation between AMH and AFC, TT, HOMA-IR, IRI. Additionally, a negative correlation between AMH and SHBG was seen in the later patient group. Increased levels of AMH in all PCOS patients in our study, in comparison with the accepted norm, indicates on possibility of using this data in the diagnosis of PCOS. AMH levels in PCOS patients with and without insulin resistance do not differ significantly. The correlation between AMH and the morphological characteristics of ovaries has been established.


Assuntos
Hormônio Antimülleriano/genética , Hormônio Foliculoestimulante/genética , Resistência à Insulina , Hormônio Luteinizante/genética , Folículo Ovariano/metabolismo , Síndrome do Ovário Policístico/genética , Adolescente , Adulto , Hormônio Antimülleriano/sangue , Biomarcadores/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Expressão Gênica , Humanos , Insulina/sangue , Hormônio Luteinizante/sangue , Tamanho do Órgão , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/patologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico por imagem , Síndrome do Ovário Policístico/patologia , Globulina de Ligação a Hormônio Sexual/genética , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Testosterona/genética , Ultrassonografia
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