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1.
Am J Gastroenterol ; 115(2): 216-223, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31658123

RESUMO

OBJECTIVES: Sex hormones have been hypothesized to explain the strong male predominance in esophageal adenocarcinoma, but evidence is needed. This study examined how circulating sex hormone levels influence future risk of esophageal adenocarcinoma. METHODS: This case-control study was nested in a prospective Norwegian cohort (Janus Serum Bank Cohort), including 244 male patients with esophageal adenocarcinoma and 244 male age-matched control participants. Associations between prediagnostic circulating levels of 12 sex hormones and risk of esophageal adenocarcinoma were assessed using conditional logistic regression. In addition, a random-effect meta-analysis combined these data with a similar prospective study for 5 sex hormones. RESULTS: Decreased odds ratios (ORs) of esophageal adenocarcinoma were found comparing the highest with lowest quartiles of testosterone (OR = 0.44, 95% confidence interval [CI] 0.22-0.88), testosterone:estradiol ratio (OR = 0.37, 95% CI 0.19-0.72), and luteinizing hormone (OR = 0.50, 95% CI 0.30-0.98), after adjustment for tobacco smoking and physical activity. These associations were attenuated after further adjustment for body mass index (OR = 0.56, 95% CI 0.27-1.13 for testosterone; OR = 0.46, 95% CI 0.23-0.91 for testosterone:estradiol ratio; OR = 0.55, 95% CI 0.29-1.08 for luteinizing hormone). No associations were observed for sex hormone-binding globulin, dehydroepiandrosterone sulfate, follicle-stimulating hormone, prolactin, 17-OH progesterone, progesterone, androstenedione, or free testosterone index. The meta-analysis showed an inverse association between testosterone levels and risk of esophageal adenocarcinoma (pooled OR for the highest vs lowest quartile = 0.60, 95% CI 0.38-0.97), whereas no associations were identified for androstenedione, sex hormone-binding globulin, estradiol, or testosterone:estradiol ratio. DISCUSSION: Higher circulating testosterone levels may decrease the risk of esophageal adenocarcinoma in men.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasias Esofágicas/epidemiologia , Hormônios Esteroides Gonadais/metabolismo , Gonadotropinas Hipofisárias/metabolismo , Globulina de Ligação a Hormônio Sexual/metabolismo , 17-alfa-Hidroxiprogesterona/metabolismo , Adenocarcinoma/metabolismo , Adulto , Androstenodiona/metabolismo , Estudos de Casos e Controles , Sulfato de Desidroepiandrosterona/metabolismo , Neoplasias Esofágicas/metabolismo , Estradiol/metabolismo , Hormônio Foliculoestimulante/metabolismo , Humanos , Modelos Logísticos , Hormônio Luteinizante/metabolismo , Masculino , Pessoa de Meia-Idade , Noruega , Progesterona/metabolismo , Prolactina/metabolismo , Estudos Prospectivos , Fatores de Risco , Testosterona/metabolismo
2.
Andrologia ; 51(11): e13410, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637758

RESUMO

Phoenixin (PNX) and nesfatin-1 are localised in the hypothalamus and the pituitary gland. Moreover, the most of the PNX-expressing neurons in the hypothalamus also co-express nesfatin-1. These outcomes may suggest that there is an interaction between PNX and nesfatin-1, at least in terms of neuroendocrine-mediated regulations. Hence, the study was planned to find out the effects of centrally delivered PNX and nesfatin-1 on male sex hormones or to show the interactive association of intracerebroventricularly (ICV) injected PNX+nesfatin-1 combination on the release of male hormones. PNX and nesfatin-1, single or together, were delivered ICV to different male Wistar Albino rat groups. Both PNX and nesfatin-1 induced a significant enhancement in plasma FSH, LH and testosterone without inducing any alteration in plasma GnRH in the rats. The central combinatorial treatment of both the neuropeptides produced a more potent rise in male plasma hormone levels than treating with single neuropeptide. In summary, our preliminary data show that centrally delivered PNX and nesfatin-1 can affect plasma male hormone levels. Moreover, that the combinatorial treatment with both the neuropeptides in male rats leading to a more potent effect on the plasma male hormone levels might suggest that both these neuropeptides act synergistically in terms of regulation of male HPGA.


Assuntos
Hormônio Liberador de Gonadotropina/sangue , Gonadotropinas Hipofisárias/sangue , Hormônios Hipotalâmicos/fisiologia , Nucleobindinas/fisiologia , Hormônios Peptídicos/fisiologia , Testosterona/sangue , Animais , Masculino , Ratos Wistar
3.
PLoS Comput Biol ; 15(8): e1006662, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31437161

RESUMO

Pituitary endocrine cells fire action potentials (APs) to regulate their cytosolic Ca2+ concentration and hormone secretion rate. Depending on animal species, cell type, and biological conditions, pituitary APs are generated either by TTX-sensitive Na+ currents (INa), high-voltage activated Ca2+ currents (ICa), or by a combination of the two. Previous computational models of pituitary cells have mainly been based on data from rats, where INa is largely inactivated at the resting potential, and spontaneous APs are predominantly mediated by ICa. Unlike in rats, spontaneous INa-mediated APs are consistently seen in pituitary cells of several other animal species, including several species of fish. In the current work we develop a computational model of gonadotropin releasing cells in the teleost fish medaka (Oryzias latipes). The model stands out from previous modeling efforts by being (1) the first model of a pituitary cell in teleosts, (2) the first pituitary cell model that fires sponateous APs that are predominantly mediated by INa, and (3) the first pituitary cell model where the kinetics of the depolarizing currents, INa and ICa, are directly fitted to voltage-clamp data. We explore the firing properties of the model, and compare it to the properties of previous models that fire ICa-based APs. We put a particular focus on how the big conductance K+ current (IBK) modulates the AP shape. Interestingly, we find that IBK can prolong AP duration in models that fire ICa-based APs, while it consistently shortens the duration of the predominantly INa-mediated APs in the medaka gonadotroph model. Although the model is constrained to experimental data from gonadotroph cells in medaka, it may likely provide insights also into other pituitary cell types that fire INa-mediated APs.


Assuntos
Gonadotrofos/metabolismo , Modelos Biológicos , Oryzias/metabolismo , Potenciais de Ação , Animais , Cálcio/metabolismo , Biologia Computacional , Simulação por Computador , Feminino , Proteínas de Peixes/metabolismo , Gonadotropinas Hipofisárias/metabolismo , Canais Iônicos/metabolismo , Cinética , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo
4.
Dis Markers ; 2019: 2384069, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467615

RESUMO

Recent studies have suggested that a low concentration of follicle-stimulating hormone (FSH) is associated with a higher prevalence of metabolic disturbances in postmenopausal women. In this study, we aim to evaluate the association between FSH, luteinizing hormone (LH), and LH/FSH ratio values and the risk of insulin resistance (HOMA-IR >2.0), prediabetes (IFG), and type 2 diabetes in a 5-year prospective study in postmenopausal women. 114 postmenopausal women were divided into 4 groups: group 1 (baseline and follow-up normoglycemic women), group 2 (normoglycemic women at baseline progressing to IFG), group 3 (women with baseline and follow-up IFG), and group 4 (women with baseline IFG progressing to diabetes). Baseline and follow-up anthropometric measurements and blood collections were performed. Serum/plasma was assayed for glucose, HDL-C, TG, C-reactive protein (CRP), 17beta-estradiol, estrone, insulin, thyroid-stimulating hormone (TSH), FSH, and LH. Homeostatic model assessment of insulin resistance (HOMA-IR) and LH/FSH ratios were calculated. The baseline concentrations of FSH and LH statistically decreased across all four groups (the highest concentrations in group 1 and the lowest in group 4; p < 0.001). A logistic regression analysis showed that a 1 SD decrease in the z-score of FSH concentration is associated with a threefold increased risk of IFG and a fivefold increased risk of HOMA-IR of >2.0 and diabetes. The LH concentration had odds ratio (OR) values about two times lower than the FSH concentration. The ORs of the LH/FSH ratio were only significant for IFG. In conclusion, FSH concentration is strongly associated with insulin resistance, prediabetes, and diabetes in postmenopausal women with normal or impaired fasting glucose. LH and the LH/FSH ratio are also related to metabolic disturbances after menopause, yet to a lesser extent.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Gonadotropinas Hipofisárias/sangue , Pós-Menopausa/sangue , Estado Pré-Diabético/sangue , Biomarcadores/sangue , Glicemia/análise , Proteína C-Reativa/análise , Diabetes Mellitus Tipo 2/epidemiologia , Estradiol/sangue , Feminino , Humanos , Insulina/sangue , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Tireotropina/sangue
5.
Eur J Endocrinol ; 181(3): 275-285, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31269469

RESUMO

Objective: Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm which can infiltrate any organ or tissue. Endocrine involvement has mostly been described in case reports and small retrospective studies. We aimed to describe endocrine manifestations in a large cohort of adulthood onset (AO) and childhood onset (CO) patients with LCH. Design: Single-center observational study conducted between January 2002 and December 2017 at Pitié-Salpêtrière University Hospital (Paris, France), a tertiary care hospital. Method: Clinical, biological and morphological evaluations of pituitary, gonadal, adrenal and thyroid function evaluations performed in 63 consecutive patients with LCH (AO patients: 40, CO patients: 23). Fifty-eight patients underwent follow-up assessments. Results: Complete pituitary evaluation was performed in 38/63 patients (60.3%); at least one anterior pituitary dysfunction (APD) was found in 63.2% of them. In this subgroup of patients, the most prevalent deficiencies were diabetes insipidus (DI) and GHD (55.3% each), followed by gonadotropin deficiency (34.2%) and thyrotropin deficiency (23.7%). In the subgroup of the 25 incompletely evaluated patients, we found DI in 44%, GHD in 50%, gonadotropin deficiency in 30.4% and thyrotropin deficiency in 16%. APD was more common in CO patients (P = 0.003) but was not systematically associated with DI regardless of the age of onset. Endocrine dysfunction was most often permanent; moreover, occurrence of new deficiencies has been described during follow-up. Conclusion: The spectrum of endocrine disorders appears to be large in LCH (both in AO and CO patients) and should be evaluated carefully at diagnosis and during follow-up. APD was not always associated with DI.


Assuntos
Doenças do Sistema Endócrino/sangue , Doenças do Sistema Endócrino/diagnóstico por imagem , Sistema Endócrino/metabolismo , Histiocitose de Células de Langerhans/sangue , Histiocitose de Células de Langerhans/diagnóstico por imagem , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Doenças do Sistema Endócrino/epidemiologia , Feminino , Seguimentos , França/epidemiologia , Gonadotropinas Hipofisárias/sangue , Histiocitose de Células de Langerhans/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hormônios Tireóideos/sangue , Adulto Jovem
6.
Andrologia ; 51(8): e13318, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31131463

RESUMO

Male infertility is adversely affected by tobacco cigarette smoking. Herein, the effects of prenatal waterpipe tobacco smoke (WTS) exposure on reproductive hormones and oxidative stress of adult offspring rats were evaluated. Pregnant rats received either fresh air or mainstream WTS (2 hr daily). Pregnancy outcomes, circulatory levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin, testicular levels of oestrogen, testosterone and oxidative stress biomarkers [catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS)] were assessed in their adult male offspring rats. Prenatal WTS exposure reduced the number of born offspring, female to pups ratio and birthweight (p < 0.05). Prenatal WTS exposure increased the circulatory levels of FSH and the testicular levels of oestrogen, testosterone and TBARS and catalase activity compared with control group (p < 0.05). However, GPx activity was reduced by WTS exposure (p < 0.05). There appeared to be a trend of increased LH and prolactin levels with prenatal WTS exposure; however, it was not statistically significant compared with control group (p > 0.05). The activity of SOD was not affected by prenatal WTS exposure (p > 0.05). In conclusion, prenatal WTS exposure altered reproductive hormones as well as oxidative stress biomarkers in adult male offspring rats.


Assuntos
Infertilidade Masculina/patologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Fumar Tabaco/efeitos adversos , Tabaco para Cachimbos de Água/toxicidade , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Modelos Animais de Doenças , Estrogênios/análise , Estrogênios/metabolismo , Feminino , Gonadotropinas Hipofisárias/sangue , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/etiologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo , Testículo/patologia , Testosterona/análise , Testosterona/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
7.
Gen Comp Endocrinol ; 281: 17-29, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085192

RESUMO

Previous studies revealed an estradiol (E2)-dependent peak in brain activity, including neurosteroidogenesis and neurogenesis in the black porgy during the gonadal differentiation period. The brain-pituitary-gonadotropic axis is a key regulator of reproduction and may also be involved in gonadal differentiation, but its activity and potential role in black porgy during the gonadal differentiation period is still unknown. The present study analyzed the expression of regulatory factors involved in the gonadotropic axis at the time of gonadal differentiation (90, 120, 150 days after hatching [dah]) and subsequent testicular development (180, 210, 300 dah). In agreement with previous studies, expression of brain aromatase cyp19a1b peaked at 120 dah, and this was followed by a gradual increase during testicular development. The expression of gonadotropin subunits increased slightly but not significantly during gonadal differentiation and then increased significantly at 300 dah. In contrast, the expression of brain gnrh1 and pituitary gnrh receptor 1 (gnrhr1) exhibited a pattern with two peaks, the first at 120 dah, during the period of gonadal differentiation, and the second peak during testicular development. Gonad fshr and lhcgr increased during gonadal differentiation period with highest transcript level in prespawning season during testicular development. This suggests that the early activation of brain gnrh1, pituitary gnrhr1 and gths, and gonad gthrs might be involved in the control of gonadal differentiation. E2 treatment increased brain cyp19a1b expression at each sampling time, in agreement with previous studies in black porgy and other teleosts. E2 also significantly stimulated the expression of pituitary gonadotropin subunits at all sampling times, indicating potential E2-mediated steroid feedback. In contrast, no significant effect of E2 was observed on gnrh1. Moreover, treatment of AI or E2 had no statistically significant effect on brain gnrh1 transcription levels during gonadal differentiation. This indicated that the early peak of gnrh1 expression during the gonadal differentiation period is E2-independent and therefore not directly related to the E2-dependent peak in brain neurosteroidogenesis and neurogenesis also occurring during this period in black porgy. Both E2-independent and E2-dependent mechanisms are thus involved in the peak expression of various genes in the brain of black porgy at the time of gonadal differentiation.


Assuntos
Encéfalo/metabolismo , Estradiol/farmacologia , Perciformes/fisiologia , Hipófise/metabolismo , Diferenciação Sexual , Testículo/crescimento & desenvolvimento , Animais , Aromatase/genética , Aromatase/metabolismo , Inibidores da Aromatase/farmacologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gonadotropinas Hipofisárias/genética , Gonadotropinas Hipofisárias/metabolismo , Masculino , Perciformes/genética , Perciformes/crescimento & desenvolvimento , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores LHRH/genética , Receptores LHRH/metabolismo , Diferenciação Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo
9.
J Steroid Biochem Mol Biol ; 185: 184-188, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30172682

RESUMO

Hyper androgen state frequently can be diagnosed in bulimic women. Eating disorder not otherwise specified (EDNOS) recognized as a less severe form of bulimia nervosa (BN). The objective of the study was to determine whether androgen levels and androgen origin differs in bulimic women compared to control subjects. Forty-six women with bulimia nervosa (BN), 31 with eating disorder not otherwise specified, purging type (EDNOS P) and 56 matched healthy controls were studied with respect to serum testosterone (T), 5alpha-dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), deyhydroepiahndrosterone sulfate (DHEAS) and luteinizing hormone (LH) and to ovarian morphology. Despite all groups had almost identical androgen and SHBG levels; there were differences in the origin of circulating T and DHT. Correlation analysis suggest major differences in the formation of circulating testosterone (T) and 5α-dihydrotestosterone (DHT) with BN being more like the control subjects with peripheral formation from 4-androsterne-3,17-dione (A-4), dehydroepiandrosterone sulfate (DHEAS) and also from T. While in EDNOS group a possible direct ovarian T secretion and a DHEAS modulating action of androgens on pituitary gonadotropin secretion is present. The origin of circulating T and DHT differs between bulimics. Our findings do probably not reflect direct actions of circulating DHT on pituitary LH secretion in the women with EDNOS, but rather the effect of A-4, T via conversion to DHT in the central nervous system, indicating psych/endocrine differences between the two groups of bulimic women.


Assuntos
Androgênios/sangue , Bulimia Nervosa/sangue , Sulfato de Desidroepiandrosterona/sangue , Di-Hidrotestosterona/sangue , Hormônio Luteinizante/sangue , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Adulto , Feminino , Gonadotropinas Hipofisárias/metabolismo , Humanos , Distúrbios Menstruais/complicações , Folículo Ovariano/fisiologia
10.
J Pediatr Surg ; 54(4): 809-814, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29706444

RESUMO

PURPOSE: A meta-analysis including 11,900 cases showed that maternal gestational smoking was associated with increased risk of cryptorchidism. The aim of study was to investigate whether a hormone profile of cryptorchid boys and a supplementing histopathological evaluation of testicular biopsies could add detailed knowledge to the impact of maternal gestational smoking on pathogenesis of cryptorchidism. METHODS: 601 cryptorchid boys aged 4 months to 14 years old were included. Because normal hormones have a pronounced age dependency, we compared results from boys whose mothers had smoked heavily (>10 cigarettes/day) during pregnancy with age matched cryptorchid controls of nonsmoking mothers (1:6). We studied: birthweight, germ-cell number/tubular cross section, frequency of germ cells positive for placental-like alkaline phosphatase (PLAP), gonadotropins and inhibin-B. RESULTS: 501 boys were sons of nonsmokers, 72 boys of intermittent smokers and 28 boys of heavy smokers. 39%, 44% and 61% respectively had bilateral cryptorchidism. Compared to age-matched cryptorchid controls of nonsmoking mothers, sons of heavy smokers had lower birthweight (p = 0.006), germ-cell number/tubular cross section (p = 0.009), frequency of germ cells positive for PLAP (p = 0.037) and inhibin-B (p = 0.042). CONCLUSIONS: All findings could be associated with placental dysfunction with altered human chorionic gonadotropin production well described in women smoking during pregnancy. TYPE OF STUDY: Prognosis study (prospective cohort study with >80% follow-up). LEVEL OF EVIDENCE: Level 1.


Assuntos
Criptorquidismo/patologia , Inibinas/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Espermatozoides/patologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Criptorquidismo/sangue , Feminino , Gonadotropinas Hipofisárias/sangue , Humanos , Lactente , Masculino , Gravidez , Estudos Prospectivos , Testículo/patologia
11.
Med Sci Monit ; 24: 6774-6780, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30252834

RESUMO

BACKGROUND The aim of this study was to compare androgen levels, endocrine and metabolic indices, and clinical findings in women with polycystic ovary syndrome (PCOS) in Uygur and Han ethnic groups from Xinjiang Province, China. MATERIAL AND METHODS Between January 2016 to May 2017 clinical data were collected from Uygur (N=82) and Han (N=100) women diagnosed with PCOS, including age, body mass index (BMI), the Ferriman-Gallwey (mFG) hirsutism score, and waist-to-hip ratio (WHR). Blood samples obtained from all study participants were used to measure androgenic steroid levels, including androgen, androstenedione, dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and the free androgen index (FAI). Endocrine indices measured included sex-hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and prolactin (PL). Metabolic indices measured included insulin, glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), triglyceride (TG), and low-density lipoprotein (LDL). RESULTS The FAI in Uygur women with PCOS (4.89) was significantly increased compared with Han women with PCOS (2.78) (p<0.05); androgen levels were significantly correlated with the FAI, glucose, insulin, TC, HDL, and LDL (p<0.05); androstenedione levels were positively correlated with glucose and insulin levels (p<0.05). In Han women with PCOS, androgen levels were negatively correlated with TG levels and positively correlated with TC levels (p<0.05); the FAI was positively correlated with glucose and insulin levels (p<0.05). CONCLUSIONS There were significant differences in androgen levels, endocrine, and metabolic indices in women with PCOS between the Uygur and Han ethnic groups from Xinjiang Province in China.


Assuntos
Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Androgênios/análise , Androgênios/sangue , Androstanóis/análise , Androstanóis/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Pesos e Medidas Corporais , China , Grupos Étnicos/genética , Feminino , Gonadotropinas Hipofisárias/análise , Gonadotropinas Hipofisárias/sangue , Humanos , Insulina/sangue , Resistência à Insulina , Lipoproteínas/análise , Lipoproteínas/sangue , Obesidade/sangue , Testosterona/sangue , Triglicerídeos/sangue
12.
Domest Anim Endocrinol ; 65: 95-100, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30086525

RESUMO

Work in cattle and rodents has shown that resistin, in addition to its roles in insulin resistance and inflammation, is involved in the regulation of gonadal steroidogenesis. However, the role of resistin in the regulation of reproductive processes in other species, such as seasonally breeding sheep, is completely unknown. Herein, we tested the hypothesis that resistin can influence the secretion of anterior pituitary hormones and that its effect in ewes is dependent on the day length. Thirty Polish Longwool ewes, a breed that exhibits a strong seasonal reproductive pattern, were ovariectomized with estrogen replacement using subcutaneously inserted estradiol implants. Ewes were fed ad libitum and housed under a natural photoperiod (longitude: 19°57' E, latitude: 50° 04' N). Intravenous treatments consisted of control or recombinant bovine resistin (rbresistin) in saline: (1) control (saline; n = 10), (2) low resistin dose (1.0 µg/kg BW; n = 10), and (3) high resistin dose (10.0 µg/kg BW; n = 10). Experiments were conducted during both short-day (SD) and long-day (LD) seasons using 5 sheep per group within each season. Blood samples were collected every 10 min over 4 h. Blood plasma concentrations of FSH, LH, and prolactin (PRL) were assayed using RIA. A season × dose interaction was observed for all hormonal variables measured. Greater concentrations (P < 0.001) of LH and FSH were observed during SDs than during LDs in all groups. During SDs, the high dose (10 µg/kg BW) decreased (P < 0.001) basal LH levels and amplitude (P < 0.05) of LH pulses and increased (P < 0.001) circulating concentrations of FSH. However, the low dose of resistin decreased (P < 0.001) FSH concentrations compared to those of controls. During LDs, both the low and high resistin doses increased mean concentrations of LH (P < 0.001 and P < 0.05, respectively) and FSH (P < 0.001). A high dose of rbresistin increased (P < 0.001) the mean circulating concentrations of PRL during both seasons. However, in all groups, concentrations of PRL were greater during LDs than SDs. These results demonstrate for the first time that resistin is involved in the regulation of pituitary hormone secretion and that this effect is differentially mediated during LDs and SDs.


Assuntos
Gonadotropinas Hipofisárias/metabolismo , Adeno-Hipófise/metabolismo , Resistina/fisiologia , Estações do Ano , Ovinos/fisiologia , Animais , Relação Dose-Resposta a Droga , Implantes de Medicamento , Estradiol/administração & dosagem , Feminino , Hormônio Foliculoestimulante/sangue , Gonadotropinas Hipofisárias/sangue , Hormônio Luteinizante/sangue , Ovariectomia , Fotoperíodo , Prolactina/sangue , Resistina/administração & dosagem , Resistina/farmacologia
13.
Math Biosci ; 305: 29-41, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30075152

RESUMO

The neuroendocrine systems of the hypothalamus are critical for survival and reproduction, and are highly conserved throughout vertebrate evolution. Their roles in controlling body metabolism, growth and body composition, stress, electrolyte balance and reproduction have been intensively studied, and have yielded a rich crop of original and challenging insights into neuronal function, insights that circumscribe a vision of the brain that is quite different from conventional views. Despite the diverse physiological roles of pituitary hormones, most are secreted in a pulsatile pattern, but arising through a variety of mechanisms. An important exception is vasopressin which uses bursting neural activity, but produces a graded secretion response to osmotic pressure, a sustained robust linear response constructed from noisy, nonlinear components. Neuroendocrine systems have many features such as multiple temporal scales and nonlinearity that make their underlying mechanisms hard to understand without mathematical modelling. The models presented here cover the wide range of temporal scales involved in these systems, including models of single cell electrical activity and calcium dynamics, receptor signalling, gene expression, coordinated activity of neuronal networks, whole-organism hormone dynamics and feedback loops, and the menstrual cycle. Many interesting theoretical approaches have been applied to these systems, but important problems remain, at the core the question of what is the true advantage of pulsatility.


Assuntos
Modelos Neurológicos , Neuroendocrinologia , Sistemas Neurossecretores/fisiologia , Hormônio Adrenocorticotrópico/fisiologia , Animais , Feminino , Gonadotropinas Hipofisárias/fisiologia , Hormônio do Crescimento/fisiologia , Humanos , Hipotálamo/fisiologia , Masculino , Conceitos Matemáticos , Ejeção Láctea/fisiologia , Neurossecreção/fisiologia , Ocitocina/fisiologia , Hipófise/fisiologia , Gravidez , Prolactina/fisiologia , Tireotropina/fisiologia , Vasopressinas/fisiologia
14.
Expert Opin Drug Discov ; 13(9): 799-813, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30073857

RESUMO

INTRODUCTION: Pituitary gonadotropins play an essential and pivotal role in the control of human and animal reproduction within the hypothalamic-pituitary-gonadal (HPG) axis. The computational modeling of pituitary gonadotropin signaling encompasses phenomena of different natures such as the dynamic encoding of gonadotropin secretion, and the intracellular cascades triggered by gonadotropin binding to their cognate receptors, resulting in a variety of biological outcomes. Areas covered: The authors provide an overview of the historical and ongoing issues in modeling and data analysis related to gonadotropin secretion in the field of both physiology and neuroendocrinology. They mention the different mathematical formalisms involved, their interest and limits. They also discuss open statistical questions in signal analysis associated with key endocrine issues and review recent advances in the modeling of the intracellular pathways activated by gonadotropins, which yields promising development for innovative approaches in drug discovery. Expert opinion: The greatest challenge to be tackled in computational modeling of pituitary gonadotropin signaling is the embedding of gonadotropin signaling within its natural multi-scale environment, from the single cell level, to the organic and whole HPG level. The development of modeling approaches of G protein-coupled receptor signaling, together with multicellular systems biology may lead to unexampled mechanistic understanding with critical expected fallouts in the therapeutic management of reproduction.


Assuntos
Simulação por Computador , Descoberta de Drogas/métodos , Gonadotropinas Hipofisárias/metabolismo , Animais , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Modelos Teóricos , Receptores Acoplados a Proteínas-G , Reprodução/fisiologia , Transdução de Sinais/fisiologia , Biologia de Sistemas/métodos
15.
J Am Acad Dermatol ; 79(6): 1133-1140.e3, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30055204

RESUMO

BACKGROUND: The role of female sex hormones in the pathogenesis of malignant melanoma (MM) remains controversial. Although melanocytes appear to be hormonally responsive, the effect of estrogen on MM cells is less clear. Available clinical data does not consistently demonstrate that increased endogenous hormones from pregnancy or increased exogenous hormones from oral contraceptive pills and hormone replacement affect MM prevalence and outcome. OBJECTIVE: We sought to examine potential associations between in vitro fertilization (IVF) and melanoma. METHODS: A literature review was conducted. Primary outcomes were reported as associations between IVF and melanoma risk compared with the general population. Secondary outcomes included associations stratified by type of IVF regimen and subgroup, such as parous versus nulliparous patients. RESULTS: Eleven studies met our inclusion criteria. Five studies found no increased risk for MM among IVF users compared with the general population. Two studies found an increase in MM in clomiphene users, and 4 studies found an increase in MM among patients who were gravid or parous either before or after IVF. CONCLUSION: The reviewed studies do not reveal consistent patterns of association between IVF and MM among all infertile women. However, the data indicates a potential increased risk for MM in ever-parous patients treated with IVF. High-quality studies including a large number of MM cases that control for well-established MM risk factors are needed to adequately assess the relationship between IVF and MM, particularly among ever-parous women.


Assuntos
Clomifeno/efeitos adversos , Estrogênios , Fertilização In Vitro , Melanoma/induzido quimicamente , Neoplasias Hormônio-Dependentes/induzido quimicamente , Indução da Ovulação/efeitos adversos , Feminino , Fertilização In Vitro/métodos , Gonadotropinas Hipofisárias/efeitos adversos , Gonadotropinas Hipofisárias/farmacologia , Humanos , Infertilidade Feminina/complicações , Melanócitos/efeitos dos fármacos , Melanócitos/patologia , Melanoma/epidemiologia , Neoplasias Hormônio-Dependentes/epidemiologia , Paridade , Gravidez , Receptores Estrogênicos/efeitos dos fármacos
16.
Biochem Pharmacol ; 154: 213-221, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29753751

RESUMO

Many forms of the toxic effects produced by dioxins and related chemicals take place following activation of the aryl hydrocarbon receptor (AHR). Our previous studies have demonstrated that treating pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic dioxin, attenuates the pituitary expression of gonadotropins to reduce testicular steroidogenesis during the fetal stage, resulting in the impairment of sexually-dimorphic behaviors after the offspring reach maturity. To investigate the contribution of AHR to these disorders, we examined the effects of TCDD on AHR-knockout (AHR-KO) Wistar rats. When pregnant AHR-heterozygous rats were given an oral dose of 1 µg/kg TCDD at gestational day (GD) 15, TCDD reduced the expression of pituitary gonadotropins and testicular steroidogenic proteins in male wild-type fetuses at GD20 without affecting body weight, sex ratio and litter size. However, the same defect did not occur in AHR-KO fetuses. Further, fetal exposure to TCDD impaired the activity of masculine sexual behavior after reaching adulthood only in the wild-type offspring. Also, in female offspring, not only the fetal gonadotropins production but also sexual dimorphism, such as saccharin preference, after growing up were suppressed by TCDD only in the wild-type. Interestingly, in the absence of TCDD, deleting AHR reduced masculine sexual behavior, as well as fetal steroidogenesis of the pituitary-gonadal axis. These results provide novel evidence that 1) AHR is required for TCDD-produced defects in sexually-dimorphic behaviors of the offspring, and 2) AHR signaling plays a role in gonadotropin synthesis during the developmental stage to acquire sexual dimorphism after reaching adulthood.


Assuntos
Hipófise/metabolismo , Dibenzodioxinas Policloradas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptores de Hidrocarboneto Arílico/deficiência , Caracteres Sexuais , Testículo/metabolismo , Animais , Dioxinas/toxicidade , Poluentes Ambientais , Feminino , Gonadotropinas Hipofisárias/antagonistas & inibidores , Gonadotropinas Hipofisárias/metabolismo , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Hipófise/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Wistar , Receptores de Hidrocarboneto Arílico/agonistas , Testículo/efeitos dos fármacos
17.
Toxicol Ind Health ; 34(9): 596-608, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29759042

RESUMO

We investigated the effects of melatonin on sperm parameters and some biochemical markers in lead-exposed male Wistar rats. Lead (50 mg/kg bw/day) and/or melatonin (4 mg/kg or 10 mg/kg bw/day) was administered for 4 weeks, while 2-week lead exposure was preceded by or followed by 2-week treatment with both doses of melatonin in other groups. Lead reduced glutathione, catalase, adjusted testes weight, semen parameters but did not change malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase, and total antioxidant capacity. Though independent of prolactin, lead-induced gonadotoxicity was both centrally and peripherally mediated, as it reduced gonadotropin-releasing hormone and testosterone levels, while gonadotropin levels did not change significantly probably due to negative feedback by elevated estradiol. However, pre-, simultaneous, or posttreatment of lead-exposed rats with melatonin reduced MDA, SOD, and estradiol but dose-dependently increased other parameters. Conclusively, lead causes male gonadotoxicity through oxidative stress and endocrine mechanisms, and these could be dose-dependently prevented and ameliorated by melatonin.


Assuntos
Antioxidantes/farmacologia , Gonadotropinas Hipofisárias/sangue , Chumbo/toxicidade , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/análise , Peso Corporal/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/sangue , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos
18.
Psychosom Med ; 80(6): 564-572, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29794946

RESUMO

OBJECTIVE: Behavioral and psychosocial factors have been associated with a decline of the quality of semen. However, the relationship of depression and physical activity (PA) with semen quality remains unclear. METHODS: Data were obtained from 587 young male Chinese college students in June 2013. Participants completed a questionnaire assessing life-style factors, the Zung self-rated depression scale, and three items related to PA. They underwent a physical examination and provided a semen sample and a blood sample for reproductive hormones (testosterone, estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and prolactin). RESULTS: Men with high depression scores (n = 63, 10.7%) had lower sperm concentration (M (SD) = 66.9 (74.5) versus 72.6 (56.9) [10/ml], p = .043) and total sperm count (M (SD) = 241.6 (299.7) versus 257.0 (204.0) [10], p = .024) than nondepressed men. Participants with low PA levels (n = 99, 16.9%) had lower total sperm count (M (SD) = 204.4 (153.7) versus 265.8 (225.8) [10/ml], p = .017) than participants with higher activity levels. After adjusting for potential confounders, depressed men had 18.90% (95% confidence interval [CI] = 1.14%-33.47%) lower sperm concentration and 21.84% (95% CI = 3.39%-36.90%) lower total sperm count than nondepressed men. Men with low PA levels had 23.03% (95% CI = 2.80%-46.89%) lower total sperm count than physically active participants. An interaction effect between depression and PA on sperm concentration was detected (p = .033). There were no significant associations of depression and PA with reproductive hormones (p > .05). CONCLUSIONS: Depression and low levels of PA are associated with lower levels of semen quality, which may have implications for reproductive health.


Assuntos
Transtorno Depressivo/sangue , Exercício Físico/fisiologia , Hormônios Esteroides Gonadais/sangue , Gonadotropinas Hipofisárias/sangue , Sêmen , Adolescente , Adulto , China/epidemiologia , Transtorno Depressivo/epidemiologia , Humanos , Masculino , Contagem de Espermatozoides , Estudantes/estatística & dados numéricos , Universidades/estatística & dados numéricos , Adulto Jovem
19.
Reproduction ; 156(2): 121-132, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29794024

RESUMO

It has been demonstrated that food intake and reproductive physiology are both simultaneously modulated to optimize reproductive success under fluctuating metabolic conditions. Ghrelin (GHRL) is an orexigenic peptide identified as the endogenous ligand of the growth hormone secretagogue receptor that is being investigated for its potential role on reproduction. Considering that data available so far are still limited and characterization of GHRL action mechanism on the reproductive system has not been fully elucidated, we studied the participation of hypothalamus in GHRL effects on sperm functional activity, plasma levels of gonadotropins and histological morphology in mice testes after hypothalamic infusion of 0.3 or 3.0 nmol/day GHRL or artificial cerebrospinal fluid (ACSF) at different treatment periods. We found that GHRL 3.0 nmol/day administration for 42 days significantly reduced sperm concentration (GHRL 3.0 nmol/day = 14.05 ± 2.44 × 106/mL vs ACSF = 20.33 ± 1.35 × 106/mL, P < 0.05) and motility (GHRL 3.0 nmol/day = 59.40 ± 4.20% vs ACSF = 75.80 ± 1.40%, P < 0.05). In addition, histological studies showed a significant decrease percentage of spermatogonia (GHRL 3.0 nmol/day = 6.76 ± 0.68% vs ACSF = 9.56 ± 0.41%, P < 0.05) and sperm (GHRL 3.0 nmol/day = 24.24 ± 1.92% vs ACSF = 31.20 ± 3.06%, P < 0.05). These results were associated with a significant reduction in luteinizing hormone and testosterone plasma levels (P < 0.05). As GHRL is an orexigenic peptide, body weight and food intake were measured. Results showed that GHRL increases both parameters; however, the effect did not last beyond the first week of treatment. Results presented in this work confirm that central GHRL administration impairs spermatogenesis and suggest that this effect is mediated by inhibition of hypothalamic-pituitary-gonadal axis.


Assuntos
Grelina/fisiologia , Gonadotropinas Hipofisárias/sangue , Hipotálamo/fisiologia , Espermatogênese , Testosterona/sangue , Animais , Peso Corporal , Ingestão de Alimentos , Masculino , Camundongos , Espermatozoides/fisiologia , Testículo/ultraestrutura
20.
Biol Reprod ; 99(3): 504-513, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29757344

RESUMO

The coordination of pituitary development is complicated and requires input from multiple cellular processes. Recent research has provided insight into key molecular determinants that govern cell fate specification in the pituitary. Moreover, increasing research aimed to identify, characterize, and functionally describe the presumptive pituitary stem cell population has allowed for a better understanding of the processes that govern endocrine cell differentiation in the developing pituitary. The culmination of this research has led to the ability of investigators to recapitulate some of embryonic pituitary development in vitro, the first steps to developing novel regenerative therapies for pituitary diseases. In this current review, we cover the major players in pituitary stem/progenitor cell function and maintenance, and the key molecular determinants of endocrine cell specification. In addition, we discuss the contribution of peripheral hormonal regulation of pituitary gland development, an understudied area of research.


Assuntos
Hipófise/embriologia , Transdução de Sinais/fisiologia , Animais , Diferenciação Celular , Feminino , Expressão Gênica , Gonadotropinas Hipofisárias/biossíntese , Hormônio do Crescimento/biossíntese , Humanos , Camundongos , Células-Tronco Multipotentes/citologia , Hipófise/citologia , Gravidez , Prolactina/biossíntese , Células-Tronco/citologia , Tireotropina/biossíntese , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia
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