Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.224
Filtrar
1.
Gene ; 752: 144760, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32416252

RESUMO

BACKGROUND: PCOS is a common endocrine disorder that is characterized by hyperandrogenism and chronic anovulation and is the leading cause of female infertility. It is a heterogeneous disorder with the involvement of multiple gene and environmental interactions. This study identified variants that are known to confer susceptibility identified by Genome wide association studies (GWAS) in other ethnicities and replicated the same in individuals with PCOS of Indian ethnicity. METHODS: Study subjects (n = 600) were recruited. Blood samples, demographic and clinical details were collected after obtaining informed consent. Fifteen variants were selected from GWA studies from other ethnicities and genotyped in half of the recruited samples (n = 300) using MassARRAYiPLEX™. Replication of significant variants generated from preliminary data was carried out by PCR and direct sequencing in remainder of the samples (n = 300). Insilco analysis for significant variants was performed using software namely CADD, GWAVA, FATHMM-MKL. Relevant statistics were used to ascertain significance. RESULTS: The mean age of patients and controls was 24.26 ± 3.22 and 30.19 ± 11.21 years respectively. Of the 15 variants, 3 variants (rs13405728 in LHCGR; rs13429458 in THADA and rs2209972 IDE genes) were found to be associated with PCOS. The association was successfully replicated in an independent cohort. Insilico analysis categorized two variants (rs13429458-THADA and rs2209972-IDE genes) as deleterious. CONCLUSION: We demonstrate the association of variants in genes namely LHCGR, THADA and IDE with an increased risk of PCOS. Genotyping for these variants aids in identifying at-risk individuals which is crucial as appropriate early interventions may benefit the patient.


Assuntos
Insulisina/genética , Proteínas de Neoplasias/genética , Síndrome do Ovário Policístico/genética , Receptores do LH/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Estudos de Coortes , Grupos Étnicos/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Testes Genéticos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Índia/epidemiologia , Insulisina/metabolismo , Proteínas de Neoplasias/metabolismo , Síndrome do Ovário Policístico/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Receptores do LH/metabolismo , Análise de Sequência de DNA/métodos
2.
Gen Comp Endocrinol ; 285: 113276, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536722

RESUMO

Reproduction in vertebrates is controlled by the brain-pituitary-gonad axis, where the two gonadotropins follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) play vital parts by activating their cognate receptors in the gonads. The main purpose of this work was to study intra- and interspecies ligand promiscuity of teleost gonadotropin receptors, since teleost receptor specificity is unclear, in contrast to mammalian receptors. Receptor activation was investigated by transfecting COS-7 cells with either Fsh receptor (mdFshr, tiFshr) or Lh receptor (mdLhr, tiLhr), and tested for activation by recombinant homologous and heterologous ligands (mdFshßα, mdLhßα, tiFshßα, tiLhßα) from two representative fish orders, Japanese medaka (Oryzias latipes, Beloniformes) and Nile tilapia (Oreochromis niloticus, Cichliformes). Results showed that each gonadotropin preferentially activates its own cognate receptor. Cross-reactivity was detected to some extent as mdFshßα was able to activate the mdLhr, and mdLhßα the mdFshr. Medaka pituitary extract (MPE) stimulated CRE-LUC activity in COS-7 cells expressing mdlhr, but could not stimulate cells expressing mdfshr. Recombinant tiLhßα, tiFshßα and tilapia pituitary extract (TPE) could activate the mdLhr, suggesting cross-species reactivity for mdLhr. Cross-species reactivity was also detected for mdFshr due to activation by tiFshßα, tiLhßα, and TPE, as well as for tiFshr and tiLhr due to stimulation by mdFshßα, mdLhßα, and MPE. Tissue distribution analysis of gene expression revealed that medaka receptors, fshr and lhr, are highly expressed in both ovary and testis. High expression levels were found for lhr also in brain, while fshr was expressed at low levels. Both fshr and lhr mRNA levels increased significantly during testis development. Amino acid sequence alignment and three-dimensional modelling of ligands and receptors highlighted conserved beta sheet domains of both Fsh and Lh between Japanese medaka and Nile tilapia. It also showed a higher structural homology and similarity of transmembrane regions of Lhr between both species, in contrast to Fshr, possibly related to the substitution of the conserved cysteine residue in the transmembrane domain 6 in medaka Fshr with glycine. Taken together, this is the first characterization of medaka Fshr and Lhr using homologous ligands, enabling to better understand teleost hormone-receptor interactions and specificities. The data suggest partial ligand promiscuity and cross-species reactivity between gonadotropins and their receptors in medaka and tilapia.


Assuntos
Oryzias/metabolismo , Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Sequência de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , Feminino , Hormônio Foliculoestimulante/química , Hormônio Foliculoestimulante/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hormônio Luteinizante/química , Hormônio Luteinizante/metabolismo , Masculino , Modelos Moleculares , Receptores do FSH/genética , Receptores da Gonadotropina/metabolismo , Receptores do LH/genética , Transdução de Sinais
3.
Gen Comp Endocrinol ; 285: 113241, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400434

RESUMO

Pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh), play central roles in the control of gonadal development of vertebrates. In mammals, Fsh and Lh exclusively activate their respective cognate receptors: Fsh receptor (Fshr) in the Sertoli cell and Lh/choriogonadotropin receptor (Lhcgr) in the Leydig cell. In teleosts, the distinct functions of Fsh and Lh and information on cellular localization of their receptors are still poorly understood. Recently we established FreeStyle 293-F cell lines producing recombinant Japanese eel Fsh and Lh (reFsh and reLh), which form a single chain consisting of a common α-subunit and ß-subunits. In this study, we conducted functional analyses of reFsh and reLh, focusing on the binding specificities to their receptors and effects on testicular steroidogenesis in vitro. Assays with gonadotropin receptors-expressing COS-7 cells indicated reFsh stimulated its cognate receptor, meanwhile reLh activated both receptors. Although results of in vitro incubations showed that reFsh and reLh induced testicular 11-ketotestosterone production in a dose and time-dependent manner by upregulating expression of steroidogenic enzymes, the effective doses of reLh were apparently lower and the effects of reLh emerged faster in comparison with reFsh. Results of quantitative real-time PCR using testicular cell fractions showed that fshr and lhcgr1 mRNA were detected both in Sertoli and Leydig cells. These analyses revealed that reFsh and reLh were biologically active and hence will be useful for future studies. Moreover, our data showed that both eel Fsh and Lh acted as steroidogenic hormones through their receptors in testicular somatic cells; however, Lh was more potent on androgen production, implying differential functions on spermatogenesis.


Assuntos
Anguilla/metabolismo , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Proteínas Recombinantes/metabolismo , Esteroides/metabolismo , Testículo/metabolismo , Animais , Células COS , Linhagem Celular , Chlorocebus aethiops , Cicloeximida/farmacologia , Dactinomicina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Japão , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do FSH/genética , Receptores do LH/genética , Testosterona/análogos & derivados , Testosterona/metabolismo
4.
Genes (Basel) ; 10(12)2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842416

RESUMO

Anti-Mullerian hormone (AMH) is an important reproductive marker of ovarian reserve produced by granulosa cells (GCs) of pre-antral and early-antral ovarian follicles in several species, including cattle. This hormone plays a vital role during the recruitment of primordial follicles and follicle stimulating hormone (FSH)-dependent follicular growth. However, the regulatory mechanism of AMH expression in follicles is still unclear. In this study, we compared the expression of AMH, AMHR-II, BMP2, BMP6, FSHR, and LHCGR genes during follicular development. In-vitro expression study was performed with and without FSH for AMH, AMHR-II, BMP2, and BMP6 genes in bovine GCs which were isolated from 3-8 mm follicles. Association among the mRNA expression and hormone level was estimated. GCs were collected from small (3-8 mm), medium (9-12 mm) and large size (13 to 24 mm) follicles before, during onset, and after deviation, respectively. Further, mRNA expression, hormones (AMH, FSH, and LH), apoptosis of GCs, and cell viability were detected by qRT-PCR, ELISA, flow cytometry, and spectrophotometry. AMH, AMHR-II, BMP2, and FSHR genes were highly expressed in small and medium follicles as compared to large ones. In addition, the highest level of AMH protein (84.14 ± 5.41 ng/mL) was found in medium-size follicles. Lower doses of FSH increased the viability of bovine GCs while higher doses repressed them. In-vitro cultured GCs treated with FSH significantly increased the AMH, AMHR-II, and BMP2 expression levels at lower doses, while expression levels decreased at higher doses. We found an optimum level of FSH (25 ng/mL) which can significantly enhance AMH and BMP2 abundance (p < 0.05). In summary, AMH, AMHR-II, and BMP2 genes showed a higher expression in follicles developed in the presence of FSH. However, lower doses of FSH demonstrated a stimulatory effect on AMH and BMP2 expression, while expression started to decline at the maximum dose. In this study, we have provided a better understanding of the mechanisms regulating AMH, AMHR II, and BMP2 signaling in GCs during folliculogenesis, which would improve the outcomes of conventional assisted reproductive technologies (ARTs), such as superovulation and oestrus synchronization in bovines.


Assuntos
Hormônio Antimülleriano/genética , Bovinos/genética , Células da Granulosa/metabolismo , Animais , Hormônio Antimülleriano/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/genética , Líquido Folicular/metabolismo , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Folículo Ovariano/metabolismo , RNA Mensageiro/genética , Receptores do FSH/genética , Receptores do FSH/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo
5.
Chem Biol Interact ; 312: 108817, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499053

RESUMO

Aconitine might have reproductive toxicity and the effects of aconitine on androgen synthesis in Leydig cells remain unclear. Here, we explore how aconitine affects androgen synthesis and metabolism in rat immature Leydig cells in vitro. Immature Leydig cells were isolated from 35-day-old male Sprague Dawley rats and cultured with 0-50 µM aconitine for 3 h in combination with LH, 8Br-cAMP, 22R-hydroxycholesterol, pregnenolone, progesterone, androstenedione, testosterone, and dihydrotestosterone, respectively. Medium androgens were measured. The levels of Leydig cell mRNAs, Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Srd5a1, and Akr1c14, were measured by qPCR. ROS and apoptosis were determined after 24-h aconitine treatment. Aconitine inhibited basal androgen production in Leydig cells at 0.05 µM and the higher concentrations. Aconitine blocked pregnenolone, progesterone, and androstenedione mediated androgen outputs without affecting 22R-hydroxycholesterol-mediated androgen production at 5 µM. Aconitine also inhibited LH and 8Br-cAMP stimulated androgen outputs at 5 µM. Further investigation showed that aconitine blocked androgen synthesis via down-regulating the expression of Scarb1, Hsd3b1, Cyp17a1, and Hsd17b3. At 50 µM, aconitine also induced ROS generation and increased apoptotic rate of Leydig cells. Aconitine lowered serum testosterone levels at 1.5 mg/kg after 7 days of oral exposure from postnatal day 35. In conclusion, aconitine inhibits androgen synthesis.


Assuntos
Aconitina/farmacologia , Androgênios/metabolismo , Regulação para Baixo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismo , Testosterona/sangue , Testosterona/farmacologia
7.
Life Sci ; 233: 116694, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31351970

RESUMO

AIMS: The hypoxia-stimulated response of the endocrine system depends on the kind and duration of hypoxia. Hypoxia has been reported to stimulate testosterone (T) production in rats, but the mechanisms remain to be investigated. MATERIALS AND METHODS: Male rats were divided into two groups. The rats exposed to chronic intermittent hypoxia (CIH) at 8 h/day were housed in a hypoxic chamber (12% O2) for 14 days. Normoxic rats were used as control animals. T was measured after challenging the rat Leydig cells (LCs) with different stimulators, including hCG (0.01 IU/ml), forskolin (10-5 M), 8-bromo-cAMP (10-4 M), A23187 (10-5 M), cyclopiazonic acid (10-4 M), and androstenedione (10-8 M). Meanwhile, the LCs were incubated with trilostane (10-5 M) and/or 25-OH-hydroxycholesterol (10-5 M); thereafter the media were collected for pregnenolone assay. KEY FINDINGS: In the CIH group, plasma T levels were increased, but the serum luteinizing hormone (LH) was decreased. Furthermore, at several time intervals after hCG injection, plasma T levels were higher in the CIH group. The evoked-release of T and pregnenolone were significantly increased in the CIH group. Compared with the normoxic group, the CIH group had higher mRNA and protein expression levels of the LH receptor and CYP11A1 but not StAR. The plasma and testicular microvasculature VEGF levels were increased in the CIH group. The testicular vessel distribution was more obvious in CIH rats. SIGNIFICANCE: CIH-induced T secretion might be partially mediated by mechanisms involving the induction of LH receptor expression, testicular angiogenesis, CYP11A1 activity, 17ß-HSD activity, and calcium-related pathway.


Assuntos
Hipóxia Celular/fisiologia , Colforsina/farmacologia , Células Intersticiais do Testículo/metabolismo , Testosterona/metabolismo , Animais , Células Cultivadas , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores do LH/genética , Receptores do LH/metabolismo , Vasodilatadores/farmacologia
8.
Yonsei Med J ; 60(7): 667-678, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31250581

RESUMO

PURPOSE: The aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development. MATERIALS AND METHODS: A comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone). Maturation and developmental competence of metaphase II oocytes from control and T1D animals was evaluated by immunofluorescent and immunohistochemical detection of biomarkers and in vitro fertilization. RESULTS: Animals from both T1D models showed increased blood glucose levels, while only streptozotocin (STZ)-injected mice showed reduced body weight. Folliculogenesis, oogenesis, and preimplantation embryogenesis were impaired in both T1D mouse models. Interestingly, exogenous streptozotocin injection to induce T1D led to marked decreases in ovary size, expression of luteinizing hormone/chorionic gonadotropin receptor in the ovaries, the number of corpora lutea per ovary, oocyte maturation, and serum progesterone levels. Both T1D models exhibited significantly reduced pre-implantation embryo quality compared with controls. There was no significant difference in embryo quality between STZ-injected and AKITA diabetic mice. CONCLUSION: These results suggest that T1D affects folliculogenesis, oogenesis, and embryo development in mice. However, the physiological mechanisms underlying the observed reproductive effects of diabetes need to be further investigated.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Fertilidade , Hormônio Luteinizante/metabolismo , Oócitos/patologia , Ovário/patologia , Receptores do LH/metabolismo , Transdução de Sinais , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL
9.
Int J Mol Sci ; 20(7)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965614

RESUMO

Luteinizing hormone (LH), a pituitary gonadotropin, coupled with LH receptor (LHR) is essential for the regulation of the gonadal maturation in vertebrates. Although LH homolog has been detected by immunocytochemical analysis, and its possible role in ovarian maturation was revealed in decapod crustacean, so far there is no molecular evidence for the existence of LHR. In this study, we cloned a novel LHR homolog (named EsLHR) from the Chinese mitten crab Eriocheir sinensis. The complete sequence of the EsLHR cDNA was 2775bp, encoding a protein of 924 amino acids, sharing 71% amino acids identity with the ant Zootermopsis nevadensis LHR. EsLHR expression was found to be high in the ovary, while low in testis, gill, brain, and heart, and no expression in the thoracic ganglion, eye stalk, muscle, and hepatopancreas. Quantitative PCR revealed that the expression level of EsLHR mRNA was significantly higher in the ovaries in previtellogenic (Pvt), late vitellogenic (Lvt), and germinal vesicle breakdown (GVBD) stages than that in the vitellogenic (Mvt) and early vitellogenic (Evt) stages (P < 0.05), and, the highest and the lowest expression were in Lvt, and Evt, respectively. The strong signal was mainly localized in the ooplasm of Pvt oocyte as detected by in situ hybridization. The crab GnRH homolog can significantly induce the expression of EsLHR mRNA at 36 hours post injection in vivo (P < 0.01), suggesting that EsLHR may be involved in regulating ovarian development through GnRH signaling pathway in the mitten crab.


Assuntos
Braquiúros/metabolismo , Receptores do LH/metabolismo , Animais , Braquiúros/embriologia , DNA Complementar/metabolismo , Feminino , Masculino , Ovário/embriologia , Ovário/metabolismo , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Receptores do LH/genética , Testículo/embriologia , Testículo/metabolismo
10.
Environ Toxicol ; 34(7): 844-852, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951242

RESUMO

Our goals were to investigate whether environmentally relevant doses of T-2 toxin can affect human ovarian granulosa cells' function and to reveal the potential mechanism of T-2 toxin's action. Results showed that T-2 toxin strongly attenuated luteinizing hormone/choriogonadotropin receptor (LHCGR) mRNA expression in follicle-stimulating hormone (FSH)-stimulated human cumulus granulosa cells. Addition of human chorionic gonadotropin was not able to elicit maximal response of ovulatory genes amphiregulin, epiregulin, and progesterone receptor. T-2 toxin reduced mRNA levels of CYP19A1 and steroidogenic acute regulatory protein (STAR) and lowered FSH-stimulated estradiol and progesterone production. Mechanistic experiments demonstrated that T-2 toxin decreased FSH-stimulated cyclic adenosine monophosphate (cAMP) production. Addition of total PDE inhibitor 3-isobutyl-1-methylxanthine prevented T-2 toxin's action on LHCGR, STAR, and CYP19A1 mRNA expression in FSH-stimulated human cumulus granulosa cells. Furthermore, T-2 toxin partially decreased 8-bromoadenosine 3'5'-cyclic monophosphate (8-Br-cAMP)-stimulated LHCGR and STAR, but did not affect 8-Br-cAMP-stimulated CYP19A1 mRNA expression in human cumulus granulosa cells. Overall, our data indicate that environmentally relevant dose of T-2 toxin decreases steroidogenesis and ovulatory potency in human cumulus granulosa cells probably through activation of PDE, thus posing a significant risk for female fertility.


Assuntos
Aromatase/genética , Células do Cúmulo/efeitos dos fármacos , AMP Cíclico/metabolismo , Hormônios Esteroides Gonadais/biossíntese , Fosfoproteínas/genética , Receptores do LH/genética , Toxina T-2/farmacologia , Adulto , Aromatase/metabolismo , Células Cultivadas , Gonadotropina Coriônica/metabolismo , Células do Cúmulo/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Hormônio Foliculoestimulante/farmacologia , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Humanos , Fosfoproteínas/metabolismo , Progesterona/metabolismo , RNA Mensageiro/metabolismo , Receptores do LH/metabolismo , Adulto Jovem
11.
Gen Comp Endocrinol ; 280: 123-133, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009604

RESUMO

Receptors for follicle-stimulating hormone (Fshr), luteinizing hormone (Lhcgr1 and Lhcgr2) and androgens (Ara and Arb) transduce the hormonal signals that coordinate spermatogenesis, but the factors that regulate the abundance of these transducers in fish testes remain little-understood. To mend this paucity of information, we first determined changes in transcript abundance for these receptors (fshr, lhcgr1, ara and arb) during spermatogenesis induced by human chorionic gonadotropin (hCG) injection in the eel, Anguilla australis. We related our findings to testicular production of the fish androgen, 11-ketotestosterone (11-KT), and to the levels of the transcripts encoding steroidogenic acute regulatory protein (star) and 11ß-hydroxylase (cyp11b), and subsequently evaluated the effects of hCG or 11-KT on mRNA levels of these target genes in vitro. Testicular 11-KT production was greatly increased by hCG treatment, both in vivo and in vitro, and associated with up-regulation of star and cyp11b transcripts. In situ hybridization indicated that testicular fshr mRNA levels were higher in the early stages of hCG-induced spermatogenesis, while lhcgr1 transcripts were most abundant later, once spermatids were observed. In vitro experiments further showed that hCG and its steroidal mediator 11-KT significantly increased fshr transcript abundance. These data provide new angles on the interactions between gonadotropin and androgen signaling during early spermatogenesis. Increases in levels of 11-KT following hCG injection elevated testicular fshr mRNA levels augmenting Fsh sensitivity in the testis. This evidence is suggestive of a positive feedback loop between gonadotropins and 11-KT that may be key to regulating early spermatogenesis in fish.


Assuntos
Anguilla/genética , Regulação da Expressão Gênica , Receptores Androgênicos/genética , Receptores da Gonadotropina/genética , Testículo/metabolismo , Androgênios/metabolismo , Anguilla/sangue , Animais , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Receptores da Gonadotropina/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Esteroide 11-beta-Hidroxilase/genética , Esteroide 11-beta-Hidroxilase/metabolismo , Testículo/efeitos dos fármacos , Testosterona/análogos & derivados , Testosterona/sangue
12.
Pol J Vet Sci ; 22(1): 83-90, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30997768

RESUMO

The purpose of the study was to study the activity of the phytoestrogen genistein (GEN) act- ing on FSHR and LHR in rat ovaries with polycystic ovary syndrome (PCOS). Sixty rats were di- vided into six groups. Rats in the dose group received genistein at a concentration of either 5 (low genistein dose group, L-gen), 10 (middle genistein dose group, M-Gen) or 20 (high genistein dose group, H-Gen) mg per kg of body weight per day. Estrogen group (EG, received 0.5 mg/kg Dieth- ylstilbestrol). Concentration of sex hormones in serum was quantified by enzyme-linked immuno- sorbent assay (ELISA). Expressions of follicle-stimulating hormone receptor (FSHR) and lutein- izing hormone receptor (LHR) protein were determined by immunohistochemistry. Treatment with genistein resulted in a strong stimulation of the concentration of sex hormone in serum. The concentration of progesterone and FSH was significantly higher in H-Gen when compared to the PCOS model control group (MG) (P ⟨ 0.01). In contrast, the concentration of testosterone, LH and the ratio of LH/FSH decreased in GEN treatment groups compared to MG, the effect was statistically significant, tested by the ANOVA test (p⟨0.01). For hormone receptor activity, treat- ment with genistein resulted in an improvement of ovarian function with LHR protein expression being enhanced and FSHR protein expression being suppressed. Our results demonstrate that Genistein played a significant role in regulating FSH and LH receptor expression to improve perimenopausal ovarian and uterine function.


Assuntos
Genisteína/farmacologia , Síndrome do Ovário Policístico/metabolismo , Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Animais , Feminino , Hormônio Foliculoestimulante/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Hormônio Luteinizante , Fitoestrógenos , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Wistar
13.
Nutrients ; 11(4)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018574

RESUMO

Age-related male sexual dysfunction covers a wide variety of issues, together with spermatogenic and testicular impairment. In the present work, the effects of cordycepin (COR), an active constituent of a nutrient powerhouse Cordyceps militaris Linn, on senile testicular dysfunction in rats was investigated. The sperm kinematics, antioxidant enzymes, spermatogenic factors, sex hormone receptors, histone deacetylating sirtuin 1 (SIRT1), and autophagy-related mammalian target of rapamycin complex 1 (mTORC1) expression in aged rat testes were evaluated. Sprague Dawley rats were divided into young control (2-month-old; YC), aged control (12-month-old; AC), and aged plus COR-treated groups (5 (COR-5), 10 (COR-10), and 20 (COR-20) mg/kg). The AC group showed reduced sperm kinematics and altered testicular histomorphology compared with the YC group (p < 0.05). However, compared with the AC group, the COR-treated group exhibited improved sperm motility, progressiveness, and average path/straight line velocity (p < 0.05-0.01). Alterations in spermatogenesis-related protein and mRNA expression were significantly ameliorated (p < 0.05) in the COR-20 group compared with the AC group. The altered histone deacetylating SIRT1 and autophagy-related mTORC1 molecular expression in aged rats were restored in the COR-20 group (p < 0.05). In conclusion, the results suggest that COR holds immense nutritional potential and therapeutic value in ameliorating age-related male sexual dysfunctions.


Assuntos
Envelhecimento , Cordyceps/química , Desoxiadenosinas/farmacologia , Testículo/efeitos dos fármacos , Animais , Desoxiadenosinas/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Espermatogênese , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
Folia Histochem Cytobiol ; 57(1): 23-27, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30924919

RESUMO

INTRODUCTION: Numerous data indicate that luteinizing hormone and/or chorionic gonadotropin (LH/CG) exert direct actions on the adrenal cortex and are involved in the adrenal pathology. However, the immunohistochemical studies on the expression of LH/CG receptors (LH/CGR) in the human adrenal cortex and in the adrenocortical tumors are scarce. MATERIAL AND METHODS: Paraffin sections of samples of 6 human non-neoplastic adrenal cortex and 25 adrenocortical tumors were immunostained with anti-LH/CGR polyclonal antibody. RESULTS: All zones of the human non-neoplastic adrenal cortex present a positive immunoreaction with anti-LH/CGR antibody showing the strongest reaction in cell membranes. The LH/CGR immunostaining in the vast majority of hormonally non-functioning adenomas and in all hormone-secreting adenomas does not differ from the non-neoplastic adrenal cortex. In contrast to non-neoplastic adrenal cortex and benign adenomas, in adrenocortical cancers the immunostaining with anti-LH/CGR antibody behaves differently. The immunopositive material is almost totally filling the cytoplasm of the cells but the immunopositivity of cell membranes is weak or lacking. CONCLUSIONS: The data presented in our study show that the expression of LH/CGR in adrenocortical tumors is not ectopic but eutopic. The immunohistochemical examination of LH/CGR may be useful in the differentiation between benign and malignant lesions in the adrenal cortex. Moreover, the loss of membrane localization of LH/CGR in adrenocortical cancer suggests the alteration of receptors' function.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Córtex Suprarrenal/metabolismo , Receptores do LH/metabolismo , Córtex Suprarrenal/citologia , Neoplasias do Córtex Suprarrenal/patologia , Anticorpos/imunologia , Humanos , Imuno-Histoquímica , Receptores do LH/imunologia
15.
Neurobiol Aging ; 78: 111-120, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30925299

RESUMO

Ovariectomy (OVX), a menopause model, leads to cognition and neuronal plasticity deficits that are rescued by estrogen administration or downregulation of pituitary luteinizing hormone (LH). LH is present in the brain. However, whether LH levels differ across brain regions, change across reproductive stages, or whether brain-specific LHR signaling play a role in OVX-related cognitive and neuroplasticity losses is completely unknown. To address this, we measured brain LH in cycling and OVX C57Bl/6 across brain regions and determined whether OVX-related functional and plasticity deficits could be rescued by intracerebroventricular administration of the LHR agonist (hCG). Here, we show that while pituitary LH is increased in OVX, brain LH is decreased, primarily in spatial memory and navigation areas. Furthermore, intracerebroventricular hCG delivery after OVX rescued dendritic spine density and spatial memory. In vitro, we show that hCG increased neurite outgrowth in primary hippocampal neurons in a receptor-specific manner. Taken together, our data suggest that loss of brain LH signaling is involved in cognitive and plasticity losses associated with OVX and loss of ovarian hormones.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Hormônio Luteinizante/metabolismo , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Menopausa/fisiologia , Plasticidade Neuronal/fisiologia , Ovariectomia/efeitos adversos , Receptores do LH/metabolismo , Receptores do LH/fisiologia , Animais , Encéfalo/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Feminino , Hipocampo/fisiologia , Transtornos da Memória/prevenção & controle , Camundongos Endogâmicos C57BL , Crescimento Neuronal/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Hipófise/metabolismo , Receptores do LH/agonistas , Transdução de Sinais/fisiologia
16.
Anim Sci J ; 90(4): 473-480, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30793438

RESUMO

This study was aimed to address melatonin receptor expression, mRNA level of hypothalamus and hypophysis hormone receptors (GnRHR, FSHR, and LHR), steroidogenesis, cell cycle, apoptosis, and their regulatory factors after addition of melatonin for 24 hr in cultured buffalo granulosa cells (GCs). The results revealed that direct addition of different concentrations of melatonin (100 pM, 1 nM, and 100 nM) resulted in significant upregulation (p < 0.05) of mRNA level of melatonin receptor 1a (MT1) without affecting melatonin receptor 1b (MT2). Melatonin treatment significantly downregulated (p < 0.05) mRNA level of FSH and GnRH receptors, whereas 100 nM dose of melatonin significantly increased mRNA level of LH receptor. Treatment with 100 nM of melatonin significantly decreased the basal progesterone production with significant decrease (p < 0.05) in mRNA levels of StAR and p450ssc, and lower mRNA level of genes (Insig1, Lipe, and Scrab1) that affect cholesterol availability. Melatonin supplementation suppressed apoptosis (100 nM, p < 0.05) and enhanced G2/M phase (1 nM, 100 nM, p < 0.05) of cell cycle progression which was further corroborated by decrease in protein expression of caspase-3, p21, and p27 and increase in bcl2. Our results demonstrate that melatonin regulates gonadotrophin receptors and ovarian steroidogenesis through MT1. Furthermore, the notion of its incorporation in apoptosis and proliferation of buffalo GCs extends its role in buffalo ovaries.


Assuntos
Apoptose/efeitos dos fármacos , Estradiol/metabolismo , Hormônio Foliculoestimulante/metabolismo , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Melatonina/farmacologia , Progesterona/metabolismo , Animais , Búfalos , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Hormônio Foliculoestimulante/genética , Expressão Gênica/efeitos dos fármacos , Melatonina/fisiologia , RNA Mensageiro/metabolismo , Receptor MT1 de Melatonina/genética , Receptor MT1 de Melatonina/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Receptores LHRH/metabolismo , Regulação para Cima/efeitos dos fármacos
17.
Pathol Res Pract ; 215(4): 748-754, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30712886

RESUMO

In addition to its critical role during pregnancy, human chorionic gonadotropin (hCG) has been shown to be expressed by various tumor types. Recent studies have similarly documented the presence of the luteinizing hormone (LH)/hCG receptor (LHCGR) in a variety of nongonadal organs; however, its clinicopathological significance in ovarian cancer remains unclear. The present study used a combination of immunohistochemical, real-time PCR, and western blot analyses to examine hCG and LHCGR expression in normal and cancerous tissues collected from patients with epithelial ovarian cancer (EOC). hCG and LHCGR expression levels were resultantly shown to be significantly increased and decreased in cancerous versus normal (or benign) ovarian tissues, respectively (P < 0.05), and both expression pattern changes were associated with more advanced tumor stages and a higher rate of metastasis. Furthermore, patients with tumors with high or low levels of hCG and LHCGR, respectively, experienced a worse overall survival (OS) rate than those with low hCG or high LHCGR expression levels (P < 0.05). In fact, hCG and LHCGR expression levels were independent prognostic factors of patient OS (P < 0.05) for EOC. Collectively, these findings indicate that hCG and LHCGR expression pattern changes are associated with EOC occurrence and progression. Thus, hCG and LHCGR represent promising potential targets to improve the diagnosis, treatment, and prognosis of patients with EOC.


Assuntos
Carcinoma Epitelial do Ovário/patologia , Gonadotropina Coriônica/metabolismo , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Receptores do LH/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Gonadotropina Coriônica/genética , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Ovário/patologia , Receptores do LH/genética , Adulto Jovem
18.
Reprod Fertil Dev ; 31(4): 735-742, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30509341

RESUMO

Luteinising hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) are pituitary-derived hormones and mediate their functions through LH receptor (LHR), FSH receptor (FSHR) and PRL receptor (PRLR) respectively. This study aimed to investigate the seasonal expression patterns of LHR, FSHR and PRLR in the epididymis of the male wild ground squirrel during the breeding and non-breeding seasons. Histologically, principal cells, basal cells, cilia and mature spermatozoa were found in the lumen of caput, corpus and cauda epididymidis in the breeding season, whereas in the non-breeding season, cilia and basal cells were rarely found and the epididymidal duct was devoid of spermatozoa. Immunohistochemical results showed that LHR, FSHR and PRLR were mainly present in the filamentous cytoplasm layer of epithelial cells of the caput, corpus and cauda epididymidis and FSHR and PRLR displayed stronger staining in the breeding season than in the non-breeding season. Furthermore, the mRNA and protein levels of FSHR and PRLR in all regions of epididymis as well as the levels of LHR in the caput and cauda epididymidis were higher during the breeding season. The protein levels of FSHR, LHR and PRLR were positively correlated with epididymal weight. Together, these results suggest that LHR, FSHR and PRLR may regulate epididymal functional changes in the male wild ground squirrel during its seasonal breeding cycle.


Assuntos
Epididimo/metabolismo , Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Receptores da Prolactina/metabolismo , Estações do Ano , Animais , Masculino , Receptores do FSH/genética , Receptores do LH/genética , Receptores da Prolactina/genética , Reprodução/fisiologia , Sciuridae , Testículo/metabolismo
19.
Theriogenology ; 135: 204-212, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30522699

RESUMO

The egg production of poultry depends on follicular development and selection. Nonetheless, the mechanism underlying the priority of selecting of hierarchical follicles is completely unknown. SMAD9 is one of the important transcription factors in the BMP/SMAD pathway and is involved in goose follicular initiation. To identify its potential role in determination of the goose follicle hierarchy, we used BMP type I receptor inhibitor LDN-193189 both in vivo and in vitro and found that SMAD9 mRNA expression decreased in the presence of LDN-193189. While the level of SMAD9 mRNA decreased after treatment with LDN-193189, we found that the egg production (7.08 eggs per bird per year) of the animals increased, estradiol (E2) levels significantly increased, but the levels of progesterone (P4) remained unchanged. We also detected a significant increase in luteinizing hormone receptor (LHR) mRNA expression, but no change in follicle-stimulating hormone receptor (FSHR) mRNA amounts. The in vitro experimental results indicated that SMAD9 knockdown by RNA interference noticeably reduced E2 and P4 biosynthesis and FSHR and LHR mRNA expression in goose granulosa cells. Chromatin immunoprecipitation assay of goose granulosa cells revealed that phospho-SMAD9 bound to the LHR promoter and possibly regulated its transcriptional activity. These findings revealed that SMAD9 is differentially expressed in goose follicles, and acts as a key player in the control over goose follicular selection.


Assuntos
Anseriformes/fisiologia , Folículo Ovariano/fisiologia , RNA Mensageiro/metabolismo , Receptores do LH/metabolismo , Proteína Smad8/genética , Animais , Proliferação de Células , Regulação para Baixo , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica , Progesterona/metabolismo , RNA Mensageiro/genética , Receptores do LH/genética
20.
Environ Pollut ; 246: 217-224, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30557795

RESUMO

Bisphenol A (BPA) is widely used in consumer products and is a potential endocrine disruptor linked with abnormal development of male reproductive tract. However, its action and its effects on the pathways in the development of male gonad are still unclear. Here we report that effects of BPA exposure during gestation on male gonad development. Sprague-Dawley rats were gavaged daily with BPA (0, 4, 40, and 400 mg/kg body weight) from gestational day 12 to day 21. BPA dose-dependently decreased serum testosterone levels (0.45 ±â€¯0.08 ng/ml and 0.32 ±â€¯0.08 ng/ml for 40 and 400 mg/kg BPA, respectively) versus the control level (1.11 ±â€¯0.22 ng/ml, Mean ±â€¯SE). BPA lowered Leydig cell Insl3 and Hsd17b3 mRNA and their protein levels at doses of 40 and 400 mg/kg. BPA also lowered Leydig cell (Lhcgr, Cyp11a1, and Cyp17a1) and Sertoli cell (Amh) mRNA and their protein levels at 400 mg/kg. BPA decreased fetal Leydig cell number via inhibiting their proliferation, but it did not affect fetal Sertoli cell number. In conclusion, the current study shows that in utero exposure to BPA inhibits fetal Leydig and Sertoli cell differentiation, possibly disrupting the development of male reproductive tract.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Células Intersticiais do Testículo/efeitos dos fármacos , Fenóis/toxicidade , Células de Sertoli/efeitos dos fármacos , Testículo/embriologia , Animais , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptores do LH/metabolismo , Esteroide 17-alfa-Hidroxilase/metabolismo , Testosterona/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA