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1.
Curr Urol Rep ; 20(11): 78, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734886

RESUMO

PURPOSE OF REVIEW: Hypogonadism is a common endocrine dysfunction. This review focuses on the most up-to-date guideline for evaluation of pituitary function among men presenting with signs and symptoms of hypogonadism. RECENT FINDINGS: The clinician must differentiate between primary (testicular) and secondary (pituitary-hypothalamic or central) hypogonadisms and be aware of adult-onset hypogonadism. If gonadotropins are low or inappropriately normal, the clinician must consider potential reversible causes in the hypothalamus-pituitary axis. Also, it is critical to understand the pitfalls of testosterone testing. When clinically indicated, evaluation of other pituitary hormone functions as well as pituitary magnetic resonance imaging may be necessary. Furthermore, it is essential to recognize that pituitary incidentalomas are common. Patients with microprolactinoma are more likely to present with symptoms of sexual dysfunction while those with macroprolactinoma are more likely to present with symptoms of mass effect. Some functional pituitary tumors respond to drug therapy while other nonfunctional tumors require surgical intervention. It is important for the clinician to understand the proper work-up of the hypogonadal patient with pituitary dysfunction and when necessary to refer to an endocrinologist or a neurosurgeon.


Assuntos
Hipogonadismo/etiologia , Hipófise/fisiopatologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/terapia , Prolactinoma/complicações , Testosterona/uso terapêutico , Gonadotropinas/sangue , Humanos , Imagem por Ressonância Magnética , Masculino , Doenças da Hipófise/complicações , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/fisiopatologia , Neoplasias Hipofisárias/diagnóstico , Guias de Prática Clínica como Assunto , Prolactinoma/diagnóstico , Prolactinoma/tratamento farmacológico , Disfunções Sexuais Fisiológicas/etiologia , Doenças Testiculares/sangue , Doenças Testiculares/complicações , Doenças Testiculares/diagnóstico , Testosterona/sangue
2.
PLoS One ; 14(9): e0222239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509577

RESUMO

AIM: To investigate circulating hormonal, metabolic and inflammatory biomarker profiles in obese and non-obese middle-aged women. METHODS: A total of 110 women, aged 40-60 years, were included in this cross-sectional study. Patients were allocated, according to the occurrence of menopause and body mass index (BMI), into four groups: PM0 (premenopausal non-obese), PM1 (premenopausal obese), M0 (postmenopausal non-obese), and M1 (postmenopausal obese). Serum levels of gonadotropins, sex hormones, lipid markers, leptin, hs-CRP and interleukin-6 were obtained using either colorimetric or immunoenzymatic assays. Univariate and correlation analyses were performed among all clinical and laboratorial parameters. Principal component analysis was used to characterize subsets of biomarkers, which had their discriminatory capacity tested using discriminant function analysis. RESULTS: Levels of gonadotropins and female sex hormones were similar between PM0 and PM1 and between M0 and M1 (p > 0.05), all of them varied between PM0 and M0 (p < 0.05), but only estradiol was significantly altered in the comparison between PM1 and M1 (p = 0.027). Regarding metabolic markers, leptin was lower in PM0 than in M0 (p = 0.010) and higher in M1 than in M0 (p = 0.046). In premenopausal women, BMI correlated only to leptin, while it correlated to several other markers in postmenopausal women. A combination of FSH and leptin serum levels significantly discriminated the four groups (Wilks's lambda < 0.001, in canonical functions 1 and 2). CONCLUSION: A combined analysis of hormonal biomarkers may potentially distinguish obese from non-obese women with distinct menopause status. Further research is thus required to clarify the clinical significance of such findings.


Assuntos
Menopausa/metabolismo , Obesidade/metabolismo , Biomarcadores/sangue , Índice de Massa Corporal , Brasil/epidemiologia , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Hormônios Esteroides Gonadais/análise , Hormônios Esteroides Gonadais/sangue , Gonadotropinas/análise , Gonadotropinas/sangue , Humanos , Interleucina-6/análise , Interleucina-6/sangue , Leptina/análise , Leptina/sangue , Lipídeos/análise , Lipídeos/sangue , Menopausa/sangue , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Pós-Menopausa/sangue , Pré-Menopausa/sangue
3.
Andrologia ; 51(10): e13407, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31448444

RESUMO

Although varicoceles are a widely accepted identifiable male factor in infertile couples, the benefit of varicocele repair in improving pregnancy and live birth rates remains uncertain. The Study for Future Families obtained semen and reproductive hormone samples from US men whose partners were currently pregnant. In our analysis cohort of 709 men, a varicocele was detected by clinical examination in 56 (8%) of men. Men with varicocele had smaller left testis, and lower total and total motile sperm counts than men without varicocele. Gonadotropin levels were higher as well in men with varicocele. Interestingly, testosterone levels were also slightly higher in men with varicocele. Despite these differences, there was no difference between the groups in the time to achieve the study pregnancy or percentage of men with a previous pregnancy. We conclude that even in fertile men, varicoceles are associated with some degree of testicular hypofunction. This would support current recommendations to consider varicocele repair in male partners in infertile couples who demonstrate both a varicocele and abnormal semen parameters and after evaluation for treatable female factors.


Assuntos
Fertilidade/fisiologia , Sêmen/fisiologia , Testículo/fisiopatologia , Varicocele/fisiopatologia , Adulto , Estudos de Coortes , Feminino , Gonadotropinas/sangue , Humanos , Masculino , Gravidez , Estudos Prospectivos , Análise do Sêmen/normas , Testosterona/sangue , Varicocele/sangue , Varicocele/diagnóstico
4.
Proc Natl Acad Sci U S A ; 116(30): 15236-15243, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31285329

RESUMO

Dopamine neurons of the hypothalamic arcuate nucleus (ARC) tonically inhibit the release of the protein hormone prolactin from lactotropic cells in the anterior pituitary gland and thus play a central role in prolactin homeostasis of the body. Prolactin, in turn, orchestrates numerous important biological functions such as maternal behavior, reproduction, and sexual arousal. Here, we identify the canonical transient receptor potential channel Trpc5 as an essential requirement for normal function of dopamine ARC neurons and prolactin homeostasis. By analyzing female mice carrying targeted mutations in the Trpc5 gene including a conditional Trpc5 deletion, we show that Trpc5 is required for maintaining highly stereotyped infraslow membrane potential oscillations of dopamine ARC neurons. Trpc5 is also required for eliciting prolactin-evoked tonic plateau potentials in these neurons that are part of a regulatory feedback circuit. Trpc5 mutant females show severe prolactin deficiency or hypoprolactinemia that is associated with irregular reproductive cyclicity, gonadotropin imbalance, and impaired reproductive capabilities. These results reveal a previously unknown role for the cation channel Trpc5 in prolactin homeostasis of female mice and provide strategies to explore the genetic basis of reproductive disorders and other malfunctions associated with defective prolactin regulation in humans.


Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Doenças Genéticas Inatas/genética , Transtornos da Lactação/genética , Prolactina/deficiência , Prolactina/genética , Canais de Cátion TRPC/genética , Animais , Núcleo Arqueado do Hipotálamo/patologia , Nível de Alerta/fisiologia , Neurônios Dopaminérgicos/patologia , Retroalimentação Fisiológica , Feminino , Regulação da Expressão Gênica , Doenças Genéticas Inatas/metabolismo , Doenças Genéticas Inatas/patologia , Gonadotropinas/sangue , Gonadotropinas/genética , Homeostase/genética , Humanos , Transtornos da Lactação/metabolismo , Transtornos da Lactação/patologia , Potenciais da Membrana/fisiologia , Camundongos , Mutação , Prolactina/sangue , Prolactina/metabolismo , Reprodução/fisiologia , Transdução de Sinais , Canais de Cátion TRPC/deficiência
5.
J Urol ; 202(5): 1029-1035, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31216250

RESUMO

PURPOSE: Clomiphene citrate may be used as an off label treatment of hypogonadism. There are few long-term data on clomiphene citrate efficacy and safety when administered for more than 3 years. We assessed improvements in testosterone and hypogonadal symptoms while on clomiphene citrate for extended periods. MATERIALS AND METHODS: We performed a retrospective review to identify patients treated with clomiphene citrate for hypogonadism (baseline testosterone less than 300 ng/dl) at a total of 2 institutions from 2010 to 2018. We assessed the duration of clomiphene citrate therapy, serum testosterone levels, symptom improvement and clomiphene citrate side effects. RESULTS: A total of 400 patients underwent clomiphene citrate treatment for a mean ± SD of 25.5 ± 20.48 months (range 0 to 84). Of the patients 280 received clomiphene citrate for 3 years or less (mean 12.75 ± 9.52 months) and 120 received it for more than 3 years (mean 51.93 ± 10.52 months). Of men on clomiphene citrate for more than 3 years 88% achieved eugonadism, 77% reported improved symptoms and 8% reported side effects. Estradiol was significantly increased following clomiphene citrate treatment. Results did not significantly differ between patients treated for more than 3, or 3 or fewer years. The most common side effects reported by patients treated more than 3 years included changes in mood in 5, blurred vision in 3 and breast tenderness in 2. There was no significant adverse event in any patient treated with clomiphene citrate. CONCLUSIONS: Clomiphene citrate is not typically offered as primary treatment of hypogonadism in men who do not desire fertility preservation. These data demonstrate that clomiphene citrate is safe and effective with few side effects when used as long-term treatment of hypogonadism.


Assuntos
Clomifeno/administração & dosagem , Hipogonadismo/tratamento farmacológico , Adulto , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Estradiol/sangue , Seguimentos , Gonadotropinas/sangue , Humanos , Hipogonadismo/sangue , Masculino , Prolactina/sangue , Estudos Retrospectivos , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Testosterona/sangue , Fatores de Tempo , Resultado do Tratamento
6.
Eur J Obstet Gynecol Reprod Biol ; 238: 104-109, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31128532

RESUMO

OBJECTIVE: To determine the effect of a 3-month course of clomiphene citrate (CC) on plasma testosterone (T) level and on semen parameters in 18 infertile men with low T level and normal or low gonadotropines level. STUDY DESIGN: A retrospective study was conducted by reviewing the medical records of men referred to a university fertility medicine unit for infertility management between January 2010 and March 2015. Men treated with CC for at least 3 months were included if they presented with: RESULTS: 18 patients met the inclusion criteria. CC was prescribed for 3 months at the dose of 50 mg every 48 h. Plasma T level was assessed at baseline and after 1 month of CC administration. Semen parameters were assessed at baseline and after 3 months of CC administration. The median pre-treatment T level was 9.1 nmol/l; after 1 month of CC treatment the median post-treatment T level increased to 20.2 nmol/l (p = <0.001). Median baseline sperm concentration was 7 millions/ml with a median progressive motility of 18%. After 3 months of CC, the median post-treatment sperm concentration was 17.5 millions/ml (p = 0.024) and the median post-treatment progressive sperm motility was 18% (p = 0.40). Three natural pregnancies occurred during the treatment period. CONCLUSION: CC is an effective and inexpensive treatment to increase plasma T level in infertile men with low T level and normal or low gonadotropines level. Our study suggests that CC could increase sperm concentration even in oligospermic infertile men, without, however, a significant effect on progressive sperm motility. More powered randomized controlled trials are needed to definitively assess CC effect on sperm parameters and on natural pregnancy rates.


Assuntos
Clomifeno/uso terapêutico , Gonadotropinas/sangue , Infertilidade Masculina/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Testosterona/sangue , Adulto , Humanos , Infertilidade Masculina/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise do Sêmen , Adulto Jovem
8.
Theriogenology ; 128: 91-100, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30743108

RESUMO

Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effects. This study was designed to determine whether prenatal HMB treatment has an effect on oogenesis and folliculogenesis in the ovary of newborn piglets. HMB decreased the number of egg nests and primordial follicles and increased the pool of developing follicles compared to the control group. Although the percentage of TUNEL-positive oocytes within the egg nests was higher in HMB-treated group no increase in the Bax/Bcl-2 ratio and active caspase-3 expression was observed. Moreover, the granulosa cell proliferation index and StAR protein expression were higher in HMB-treated group. In contrast to the control group, the expression of E-cadherins was reduced after the HMB treatment. In addition, a significant increase in the serum level of gonadotropins and steroid hormones was detected in HMB-treated piglets. In conclusion, prenatal HMB treatment dysregulates hormonal homeostasis which impairs early folliculogenesis in piglets.


Assuntos
Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos , Suínos/crescimento & desenvolvimento , Valeratos/farmacologia , Animais , Caspase 3/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gonadotropinas/sangue , Homeostase/efeitos dos fármacos , Imuno-Histoquímica/veterinária , Marcação In Situ das Extremidades Cortadas , Folículo Ovariano/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
9.
J Obstet Gynaecol ; 39(3): 291-296, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30653368

RESUMO

We aimed to examine how leuprorelin has been studied for the treatment of women with endometriosis in Asia. We conducted a literature search of PubMed, the Cochrane Library and ClinicalTrials.gov. This review includes randomised trials of women with endometriosis treated with leuprorelin in Asia. Phase I-IV clinical trials published between January 1 2000 and December 31 2016 and written in English were included. Four studies were identified, showing that leuprorelin significantly improves pain and quality of life. The oestrone and oestradiol levels are decreased by leuprorelin but can be increased using an 'add-back' therapy with conjugated equine oestrogen and methoxyprogesterone. Menopause is more common in women treated with leuprorelin. The bone mineral density is reduced in women treated with leuprorelin. There are limited studies investigating the use of leuprorelin for the treatment of endometriosis in Asian populations. However, the research that has been conducted supports the use of leuprorelin in an Asian population.


Assuntos
Endometriose/tratamento farmacológico , Leuprolida/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Feminino , Gonadotropinas/sangue , Humanos , Dor/tratamento farmacológico
10.
BMJ Case Rep ; 12(1)2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30610037

RESUMO

Despite the fact that a small percentage of peri en postmenopausal women have mild elevations in human chorionic gonadotrophin (hCG) concentrations (<14 IU/L) besides high levels of gonadotrophins, a considerable number of clinicians are not aware of this phenomenon. We report a case of a 53-year-old woman with an unusually high hCG concentration (>40 IU/L) given her menopausal state. Although a pregnancy or a malignancy was unlikely on the basis of stable hCG levels, elevated gonadotrophins and a negative transvaginal ultrasound, her physicians were uncertain and chose an expectant approach by repeated testing. Ultimately, after consulting the laboratory, analytical interference was ruled out and pituitary origin of unusual high hCG level could be confirmed after conduction of a suppression test by oestrogen-progesterone hormone replacement therapy. Until that time, the patient had undergone a vast amount of laboratory tests and gynaecology consultations, resulting in an enormous amount of confusion, anxiety and overdiagnosis.


Assuntos
Gonadotropina Coriônica/sangue , Menopausa/sangue , Neoplasias/sangue , Perimenopausa/sangue , Gravidez/sangue , Diagnóstico Diferencial , Feminino , Gonadotropinas/sangue , Terapia de Reposição Hormonal/métodos , Humanos , Sobremedicalização , Menopausa/fisiologia , Menopausa/psicologia , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Perimenopausa/fisiologia , Hipófise/efeitos dos fármacos , Hipófise/fisiopatologia , Gravidez/fisiologia , Ultrassonografia/métodos
11.
J Pediatr Adolesc Gynecol ; 32(2): 117-121, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30502496

RESUMO

STUDY OBJECTIVE: To compare ovarian function between adolescents conceived using assisted reproductive technology (AcART) and adolescents who were conceived spontaneously (AcSP). DESIGN: Multicenter study of ovarian function in AcART because of male or tubal infertility. SETTING: University Hospital. PARTICIPANTS: We evaluated 22 AcART and 53 AcSP at 1-2 years after menarche. The participants were born at term (≥37 weeks of gestation) with normal birth weights (≥2500 g) from singleton pregnancies. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Differences in ovulation, reproductive hormones, and ovarian morphology. RESULTS: AcART had an older age of menarche than that of AcSP, even after adjusting for maternal age at menarche, gestational age, and birth weight (P = .027). AcART had lower incidence of ovulation (P = .021) and higher luteinizing hormone serum levels (P = .01) than those of AcSP. The incidence of oligomenorrhea and the cycle length were similar between AcART and AcSP. AcART had levels of anti-Müllerian hormone, inhibin B, follicle-stimulating hormone, estradiol, and androgens similar to those of AcSP. The ovarian morphology, ovarian volume, and follicle counts were similar in both groups. CONCLUSION: AcART had later menarche, lower ovulation rates, and higher luteinizing hormone levels than those of AcSP. Future studies should investigate whether these findings are indicative of a risk of ovarian dysfunction later in life for AcART.


Assuntos
Ovário/fisiologia , Ovulação/fisiologia , Técnicas de Reprodução Assistida/efeitos adversos , Adolescente , Feminino , Hormônios Gonadais/sangue , Gonadotropinas/sangue , Humanos , Gravidez , Gravidez na Adolescência/fisiologia , Globulina de Ligação a Hormônio Sexual/análise , Ultrassonografia
12.
J Clin Endocrinol Metab ; 104(3): 906-914, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30295816

RESUMO

Context: Clomiphene is a performance-enhancing drug commonly abused by males in sport, but the extent to which testosterone increases in healthy males following its use is unknown. In addition, evidence suggests that clomiphene, a mixture of cis- and trans-isomers zuclomiphene and enclomiphene, is detectable in urine for months following use; the isomer-specific urinary detection window has yet to be characterized in a controlled study. Objective: To determine the effect of once-daily, 30-day clomiphene treatment on serum testosterone and gonadotropin levels in the subject population studied and the urinary clearance and detection window of clomiphene isomers following administration for antidoping purposes. Participants and Design: Twelve healthy males aged 25 to 38 years, representing a recreational athlete population, participated in this open-label, single-arm study. Intervention: Oral clomiphene citrate (50 mg) was self-administered once daily for 30 days. Serum and urine samples were collected at baseline and at days 7, 14, 21, 28, 30, 32, 35, 37, 44, 51, and 58; urine collections continued periodically up to day 261. Results: Mean testosterone, LH, and FSH levels increased 146% (SEM, ±23%), 177% (±34%), and 170% (±33%), respectively, during treatment compared with baseline. Serum drug concentrations and urinary excretion were nonuniform among individuals as isomeric concentrations varied. The zuclomiphene urinary detection window ranged from 121 to >261 days. Conclusions: Clomiphene significantly raised serum testosterone and gonadotropin levels in healthy men and thus can be abused as a performance-enhancing drug. Such abuse is detectable in urine for ≥4 months following short-term use.


Assuntos
Clomifeno/efeitos adversos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Substâncias para Melhoria do Desempenho/efeitos adversos , Testículo/efeitos dos fármacos , Administração Oral , Adulto , Clomifeno/administração & dosagem , Clomifeno/urina , Doping nos Esportes/métodos , Doping nos Esportes/prevenção & controle , Hormônio Foliculoestimulante/sangue , Gonadotropinas/sangue , Gonadotropinas/metabolismo , Voluntários Saudáveis , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Hormônio Luteinizante/sangue , Masculino , Substâncias para Melhoria do Desempenho/administração & dosagem , Substâncias para Melhoria do Desempenho/urina , Autoadministração , Testículo/metabolismo , Testosterona/sangue , Testosterona/metabolismo
13.
Horm Res Paediatr ; 91(5): 336-345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30537713

RESUMO

BACKGROUND/AIMS: Mutations in the DAX1 gene cause X-linked adrenal hypoplasia congenita (AHC) classically associated with hypogonadotropic hypogonadism. Unexpectedly, precocious puberty (PP) has been reported in some cases, its mechanism remaining unclear. METHODS: We longitudinally studied a boy with AHC due to DAX1 gene mutation who developed peripheral PP at age 4.5 years. Initially he presented pubic hair, penile enlargement, advanced bone age and elevated testosterone levels. PP progressed with acne, body odour and ejaculations. In addition, we summarized reported findings of patients with DAX1 mutations and PP in the literature in a structured manner providing a basis to discuss possible pathomechanisms of PP in DAX1 patients. RESULTS: In our patient, hydrocortisone treatment was increased to 20 mg/m2/day as suggested in similar published cases. However, despite the suppression of adrenocorticotropic hormone (ACTH), this remained without clinical effect or change in laboratory results. The progression of symptoms of pubertal development was well suppressed under cyproterone acetate treatment. Twenty-four-hour steroid urine excretion rate measurements excluded an effect of adrenal androgens and showed a prepubertal rise of excreted testosterone. Testes size remained small. GnRH testing showed peripheral PP. CONCLUSION: We hypothesize that an intrinsic, gonadotropin- and ACTH-independent activation of steroidogenesis in the DAX1 deficient testes leads to PP in AHC patients with DAX1 mutations.


Assuntos
Hiperplasia Suprarrenal Congênita , Hormônio Adrenocorticotrópico/sangue , Receptor Nuclear Órfão DAX-1 , Gonadotropinas/sangue , Mutação , Puberdade Precoce , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/patologia , Pré-Escolar , Receptor Nuclear Órfão DAX-1/genética , Receptor Nuclear Órfão DAX-1/metabolismo , Humanos , Masculino , Puberdade Precoce/sangue , Puberdade Precoce/genética , Puberdade Precoce/patologia , Testículo/metabolismo , Testículo/patologia
14.
Asian J Androl ; 21(4): 332-336, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30531061

RESUMO

Inhibin B is a gonadal hormone that downregulates the pituitary production of follicle-stimulating hormone (FSH). In recent years, inhibin B has proved to be an excellent marker of spermatogenesis and even a predictive factor for the recovery of fertility in patients undergoing orchiectomy and antineoplastic treatments. We propose to study inhibin B levels in orchiectomised testicular cancer patients, in order to identify a minimum value representative of normal semen quality. This retrospective study evaluates hormonal and semen parameters of 290 normozoospermic patients attending the Laboratory of Seminology - Sperm Bank "Loredana Gandini" (Rome, Italy) for cryopreservation of seminal fluid following a diagnosis of testicular cancer (TC group) and 117 healthy, normozoospermic men as a control group (CTR group). The percentile distribution of gonadotropin and inhibin B values in the TC and CTR groups was analyzed. There was a statistically significant difference between the two groups in the levels of all hormones (P ≤ 0.001) and in all semen parameters (P < 0.05). About 20% of TC patients revealed inhibin B levels below the 5th percentile of CTR group, despite normozoospermia, and 31.4% had normal spermatogenesis in the presence of FSH values >95th percentile of CTR group. Orchiectomised patients for testicular cancer presented inhibin B levels lower than healthy patients, despite normozoospermia. Our study revealed the poor sensitivity of the current inhibin B reference range when applied to monorchidic patients, suggesting the need to establish more representative ranges to enable more appropriate counseling in relation to the patient's new endocrine condition.


Assuntos
Inibinas/sangue , Orquiectomia , Neoplasias Testiculares/sangue , Testosterona/sangue , Adulto , Gonadotropinas/sangue , Humanos , Masculino , Valores de Referência , Neoplasias Testiculares/cirurgia , Adulto Jovem
15.
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
16.
J Ovarian Res ; 11(1): 83, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241552

RESUMO

BACKGROUND: Very small embryonic-like stem cells (VSELs) exist in adult organs, express pluripotent markers and have the ability to differentiate into three germ layers in vitro. Testicular, ovarian and hematopoietic stem/progenitor cells express receptors for follicle stimulating (FSH) and ovarian hormones and are activated by them to undergo proliferation/differentiation. VSELs exist in mouse uterus and are regulated by physiological dose of estradiol (E) & progesterone (P) during endometrial growth, differentiation and regeneration/remodeling. In the present study, effects of daily administration of E (2 µg/day), P (1 mg/Kg/day) or FSH (5 IU/day) for 7 days on the endometrium and stem/progenitor cells was studied in bilaterally ovariectomized mice. RESULTS: E treatment resulted in hypertrophy whereas P resulted in hyperplasia and overcrowding of epithelial cells. FSH also directly stimulated the endometrial cells. Nuclear OCT-4A positive VSELs were visualized in ovariectomized (atrophied) endometrium and cytoplasmic OCT-4B positive epithelial, stromal and endothelial cells were observed after treatment. FSH treated uterine tissue showed presence of 4 alternately spliced FSHR isoforms by Western blotting. 3-5 µm VSELs with a surface phenotype of LIN-/CD45-/SCA-1+ were enumerated by flow cytometry and were found to express ER, PR, FSHR1 and FSHR3 by RT-PCR analysis. Differential effects of treatment were observed on pluripotent (Oct4A, Sox2, Nanog), progenitors (Oct-4, Sca-1), primordial germ cells (Stella, Fragilis) and proliferation (Pcna) specific transcripts by qRT-PCR analysis. FSH and P (rather than E) exerted profound, direct stimulatory effects on uterine VSELs. Asymmetric, symmetric divisions and clonal expansion of stem/progenitor cells was confirmed by co-expression of OCT-4 and NUMB. CONCLUSIONS: Results confirm presence of VSELs and their regulation by circulatory hormones in mouse uterus. Stem cell activation was more prominent after P and FSH compared to E treatment. The results question whether epithelial cells proliferation is regulated by paracrine influence of stromal cells or due to direct action of hormones on stem cells. VSELs expressing nuclear OCT-4A are the most primitive and pluripotent stem cells, undergo asymmetric cell division to self-renew and differentiate into epithelial, stromal and endothelial cells with cytoplasmic OCT-4B. Role of follicle stimulating and steroid hormones on the stem cells needs to be studied in various uterine pathologies.


Assuntos
Endométrio/metabolismo , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/sangue , Gonadotropinas/sangue , Útero/metabolismo , Animais , Diferenciação Celular , Feminino , Humanos , Camundongos
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(8): 675-679, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30111479

RESUMO

A 14-year-old female (social gender) patient was admitted to the hospital due to severe hypertension for 11 days. The patient had primary amenorrhea. The blood pressure was 146/90 mm Hg. The skin color was slightly black. The development of secondary sexual characteristics was poor. The labia majora could be observed in the vulva. However, the labia minora, clitoris, vagina, and hymen were absent. The levels of renin, cortisol, and sex hormone were low, while the levels of adrenocorticotropic hormone and gonadotropin were high. The levels of blood potassium and aldosterone were both normal. Radiography indicated retardation of bone age. Ultrasound examination revealed that the ovary and uterus were both absent. The patient had bilateral adrenal hyperplasia and cryptorchid testes located in both inguinal canals. The patient had a 46,XY karyotype. Whole genome sequencing revealed two homozygous mutations, c.985T>C and c.987delC, in exon 6 of the CYP17A1 gene of the patient and heterozygous mutations in the same sites of the parents. The patient was diagnosed with congenital adrenal hyperplasia-17α-hydroxylase deficiency. After treatment with hydrocortisone for 2 months, blood pressure returned to normal and the level of adrenocorticotropic hormone was reduced. According to the request of the patient and the parents, hydrocortisone was replaced with estrogen to allow the patient to live as a female. The patient also received surgical excision of cryptorchid testes to prevent gonadal malignancy. It is concluded that in the differential diagnosis of pediatric hypertension, sexual development should be considered and the levels of adrenocorticotropic hormone and cortisol should be evaluated. The rare disease 17α-hydroxylase deficiency should be considered for patients with low-renin hypertension and gonadal dysgenesis.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Hipertensão/diagnóstico , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/enzimologia , Hiperplasia Suprarrenal Congênita/genética , Hormônio Adrenocorticotrópico/sangue , Sequência de Bases , Éxons , Feminino , Gonadotropinas/sangue , Humanos , Hipertensão/sangue , Hipertensão/enzimologia , Hipertensão/genética , Dados de Sequência Molecular , Mutação Puntual , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo
18.
Dis Markers ; 2018: 1507674, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057649

RESUMO

Background. Placenta accreta spectrum (PAS) is a condition of abnormal placental invasion encompassing placenta accreta, increta, and percreta and is a major cause of severe maternal morbidity and mortality. The diagnosis of a PAS is made on the basis of histopathologic examination and characterised by an absence of decidua and chorionic villi are seen to directly adjacent to myometrial fibres. The underlying molecular biology of PAS is a complex process that requires further research; for ease, we have divided these processes into angiogenesis, proliferation, and inflammation/invasion. A number of diagnostic serum biomarkers have been investigated in PAS, including human chorionic gonadotropin (HCG), pregnancy-associated plasma protein-A (PAPP-A), and alpha-fetoprotein (AFP). They have shown variable reliability and variability of measurement depending on gestational age at sampling. At present, a sensitive serum biomarker for invasive placentation remains elusive. In summary, there are a limited number of studies that have contributed to our understanding of the molecular biology of PAS, and additional biomarkers are needed to aid diagnosis and disease stratification.


Assuntos
Proteínas Fetais/sangue , Gonadotropinas/sangue , Placenta Acreta/sangue , Proteína Plasmática A Associada à Gravidez/metabolismo , Biomarcadores/sangue , Feminino , Humanos , Placenta Acreta/metabolismo , Placenta Acreta/patologia , Gravidez
19.
Mol Cell Endocrinol ; 478: 77-83, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30048678

RESUMO

Knockout of pleomorphic adenoma gene 1 (PLAG1) in mice results in reduced fertility. To investigate whether PLAG1 is involved in reproductive control by the hypothalamo-pituitary system in males, we determined PLAG1 expression sites and compared gene expression between hypothalami and pituitary glands from Plag1 knockout and wildtype animals. Abundant expression of PLAG1 was detected throughout the pituitary gland, including gonadotropes and somatotropes. The hypothalamus also contained a large number of PLAG1-expressing cells. PLAG1 was expressed in some gonadotropin-releasing hormone neurons, but not in kisspeptin neurons. Gene ontology analysis indicated upregulation of cell proliferation in both structures, and of cholesterol biosynthesis in the hypothalamus, but functional confirmation is required. Expression levels of pituitary gonadotropins and gonadotropin-releasing hormone receptor, and of brain gonadotropin-releasing hormone and kisspeptin mRNA were unaffected in knockout mice. We conclude that PLAG1 deficiency does not have a major impact on the reproductive control by the hypothalamo-pituitary system.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Sistema Hipotálamo-Hipofisário/metabolismo , Animais , Colesterol/metabolismo , Gonadotropinas/sangue , Hormônio do Crescimento/sangue , Hipotálamo/metabolismo , Masculino , Camundongos Knockout , Hipófise/metabolismo
20.
Res Vet Sci ; 119: 182-195, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29958153

RESUMO

Meta-analysis was used to compare pigs immunocastrated (IC) with Improvac® versus physically castrated (PC) or entire male (EM) pigs. Performance and carcass data as most relevant for producers and packers were analyzed and the risk of boar taint was assessed by comparing the number of pigs exceeding the consumer thresholds of detection (ToD) for skatole and androstenone. A total of 78 articles fulfilled pre-defined inclusion criteria. Compared to PC pigs, IC pigs have a higher average daily gain (ADG; +32.54 g/day, P < 0.0001) and more favorable feed conversion ratio (FCR; -0.234 kg/kg, P < 0.0001), higher live weight and percentage lean, and lower hot carcass weight (HCW) and dressing percentage. Compared to EM pigs, IC pigs have a higher ADG (+65.04 g/day, P < 0.0001), FCR (+0.075 kg/kg, P < 0.0001), live weight and HCW, and a similar dressing percentage. Conventionally raised IC pigs yield more valuable meat compared to PC (+0.628 kg) and EM (+1.385 kg) pigs. Heavy IC pigs (HCW > 97.7 kg) destined for the production of high-quality cured products gain approximately 0.3 kg more ham than their PC counterparts, with backfat and intramuscular fat still fulfilling the requirements for high-quality cured products. The risk of exceeding the ToD for skatole and androstenone is similar in IC and PC pigs, but significantly higher in EM pigs. Results from our meta-analyses confirm growth performance advantages of IC pigs compared with PC or EM pigs, and reveal a higher gain of valuable meat and a similar risk of boar taint as estimated for PC pigs.


Assuntos
Gonadotropinas/sangue , Imunização/veterinária , Suínos/crescimento & desenvolvimento , Animais , Masculino , Carne , Orquiectomia , Carne Vermelha , Escatol
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