RESUMO
Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.
Assuntos
Autoanticorpos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Feminino , Gravidez , Finlândia/epidemiologia , Adulto , Estudos de Casos e Controles , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/sangue , Câncer Papilífero da Tireoide/sangue , Câncer Papilífero da Tireoide/epidemiologia , Adolescente , Adulto Jovem , Incidência , Autoanticorpos/sangue , Autoimunidade , Carcinoma Papilar/sangue , Carcinoma Papilar/epidemiologia , Hormônios Tireóideos/sangue , Hormônios Esteroides Gonadais/sangue , Estudos de Coortes , Tireotropina/sangue , Glândula Tireoide/imunologia , Iodeto Peroxidase/imunologiaRESUMO
PURPOSE: Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways. METHODS: This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex-hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders. RESULTS: Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI 1.03 to 1.44), androstenedione (RR 1.20, 95% CI 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI 0.98 to 1.28), estrone (RR 1.21, 95% CI 0.99 to 1.48), total estradiol (RR 1.19, 95% CI 1.02 to 1.39) and free estradiol (RR 1.22, 95% CI 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR 0.83, 95% CI 0.66 to 1.05). CONCLUSION: Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex-hormone-driven nature of postmenopausal breast cancer.
Assuntos
Neoplasias da Mama , Hormônios Esteroides Gonadais , Pós-Menopausa , Receptores de Estrogênio , Humanos , Feminino , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/etiologia , Pós-Menopausa/sangue , Pessoa de Meia-Idade , Hormônios Esteroides Gonadais/sangue , Estudos de Coortes , Receptores de Estrogênio/metabolismo , Fatores de Risco , Idoso , Estudos de Casos e Controles , Globulina de Ligação a Hormônio Sexual/metabolismo , Globulina de Ligação a Hormônio Sexual/análiseRESUMO
Males and females differ in their susceptibility to develop autoimmunity and allergy but also in their capacity to cope with infections and cancers. Cellular targets and molecular pathways underlying sexual dimorphism in immunity have started to emerge and appeared multifactorial. It became increasingly clear that sex-linked biological factors have important impact on the development, tissue maintenance and effector function acquisition of distinct immune cell populations, thereby regulating multiple layers of innate or adaptive immunity through distinct mechanisms. This review discusses the recent development in our understanding of the cell-intrinsic actions of biological factors linked to sex, sex hormones and sex chromosome complement, on immune cells, which may account for the sex differences in susceptibility to autoimmune diseases and allergies, and the sex-biased responses in natural immunity and cancer.
Assuntos
Doenças Autoimunes , Hipersensibilidade , Feminino , Masculino , Humanos , Cromossomo X , Hormônios Esteroides Gonadais/genética , Doenças Autoimunes/genética , Imunidade AdaptativaRESUMO
The present study aims to analyze the effects of developmental exposure to phthalates at environmentally relevant doses on the neural control of male and female reproduction. For this purpose, C57Bl/6J mice were exposed to di-(2-ethylexyl) phthalate (DEHP) alone (5 or 50 µg/kg/d), or DEHP (5 µg/kg/d) in a phthalate mixture. Exposure through diet started 6 weeks before the first mating and lasted until weaning of litters from the second gestation (multiparous dams). Analyses of offspring born from multiparous dams exposed to DEHP alone or in a phthalate mixture showed that females experienced a delayed pubertal onset, and as adults they had prolonged estrous cyclicity and reduced Kiss1 expression in the preoptic area and mediobasal hypothalamus. Male littermates showed a reduced anogenital distance and delayed pubertal onset compared with controls. However, in adulthood the weight of androgen-sensitive organs and hypothalamic Kiss1 expression were unaffected, suggesting normal functioning of the male gonadotropic axis. Developmental exposure to DEHP alone or in a phthalate mixture reduced the ability of intact males and ovariectomized and hormonally primed females to attract a sexual partner and to express copulatory behaviors. In addition, females were unable to discriminate between male and female stimuli in the olfactory preference test. Social interaction was also impaired in females, while locomotor activity and anxiety-like behavior in both sexes were unaffected by the treatment. The sexual deficiencies were associated with reduced expression of the androgen receptor in the preoptic area and progesterone receptor in the mediobasal hypothalamus, the key regions involved in male and female sexual behavior, respectively. Thus, the neural structures controlling reproduction are vulnerable to developmental exposure to phthalates at environmentally relevant doses in male and female mice. Adult females had an impaired gonadotropic axis and showed more affected behaviors than adult males.
Assuntos
Exposição Ambiental , Ácidos Ftálicos , Reprodução , Reprodução/efeitos dos fármacos , Masculino , Feminino , Animais , Camundongos , Ácidos Ftálicos/toxicidade , Exposição Ambiental/efeitos adversos , Camundongos Endogâmicos C57BL , Peso ao Nascer/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Dietilexilftalato/toxicidade , Comportamento Sexual Animal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Kisspeptinas/metabolismoRESUMO
BACKGROUND: The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids. CASE PRESENTATION: This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge. CONCLUSIONS: When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.
Assuntos
Doenças das Cabras , Cabras , Leiomioma , Receptores de Progesterona , Neoplasias Vaginais , Animais , Feminino , Leiomioma/veterinária , Leiomioma/patologia , Leiomioma/cirurgia , Neoplasias Vaginais/veterinária , Neoplasias Vaginais/patologia , Receptores de Progesterona/metabolismo , Doenças das Cabras/patologiaRESUMO
The pituitary gland is a small endocrine gland located below the hypothalamus. This gland releases several important hormones and controls the function of many other endocrine system glands to release hormones. Fish pituitary hormonal cells are controlled by neuroendocrine and sex steroid feedback. To study the complex pituitary function in vivo, we established an in vitro pituitary spheroid assay and evaluated its suitability for monitoring the annual reproductive physiological conditions in Takifugu rubripes, also known as torafugu, is one of the most economically important species distributed in the northwestern part of the Pacific Ocean, in the western part of the East China Sea, and in more northern areas near Hokkaido, Japan. Fish pituitary spheroids can be easily constructed in liquid or solid plates. The culture medium (L-15) made the aggregation faster than MEM (Hank's). A Rho-kinase inhibitor (Y-27632, 10 µM) and/or fish serum (2.5 %) also promoted spheroid formation. Laser confocal microscopy analysis of spheroids cultured with annual serum of both sexes revealed that luteinizing hormone (LH) synthesis has the highest peak in the final maturation stage (3 years old, May) in accordance with the highest serum sex steroid levels; in contrast, follicle stimulating hormone (FSH) synthesis has no correlation with the dose of serum or nutrients. Similarly, 3D cell propagation assays using female serum showed that total pituitary cells displayed the highest proliferation at puberty onset (2 years old, October) before half a year of the spawning season. These results indicate that pituitary spheroids are useful in vitro models for monitoring the reproductive physiological status of fish in vivo and may be applicable to the in vitro screening of environmental chemicals and bioactive compounds affecting reproductive efficiency in aquaculture.
Assuntos
Hipófise , Maturidade Sexual , Animais , Masculino , Feminino , Hormônio Luteinizante , Hormônio Foliculoestimulante , Sistema Endócrino , Hormônios Esteroides Gonadais , Esteroides , Hormônio Liberador de Gonadotropina/fisiologiaRESUMO
BACKGROUND: The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls. These hormones may be modulated by exercise to impact the overall health of females. OBJECTIVE: To determine the effects of exercise on sex steroid hormones in eumenorrheic females. METHODS: This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines in Lahore, Pakistan. The full-length articles were searched using these databases/search engines (PubMed, Web of Science and Google Scholar, Sci-Hub). Randomized controlled trials along with single group experimental studies were also included. All types of exercises were compared with no exercise in the control group. The Cochrane Risk of Bias assessment tool assessed and screened the articles. The data were then analyzed. The primary outcomes were the levels of estrogen, progesterone and testosterone. RESULTS: Eleven studies were included (5 randomized controlled trials and 6 quasi-experimental studies). The effects of exercise on free estradiol concentration and serum progesterone level were not significant [p = 0.37 (SMD = 0.33, 95% CI = 0.14 to 0.74, I2 = 0%) and p = 0.84 (S.D= -0.65, C.I= -6.92 to 5.62, I2 = 94%)] respectively, whereas, the effects on testosterone levels were significant [p value < 0.00001 (M.D = 0.89, 95% C.I= -2.16 to 3.95, I2 = 94%)]. CONCLUSION: A blinded randomized controlled trial should be conducted in which a structured approach should be followed by women along with warm-ups, cool down and rest intervals. TRIAL REGISTRATION NUMBER: The systematic review was registered prospectively on PROSPERO with registration number CRD42023473767.
Assuntos
Estrogênios , Exercício Físico , Progesterona , Testosterona , Humanos , Feminino , Progesterona/sangue , Exercício Físico/fisiologia , Testosterona/sangue , Estrogênios/sangue , Hormônios Esteroides Gonadais/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Estradiol/sangueRESUMO
BACKGROUND: The relationship of testosterone and estradiol concentrations with cognitive function among community-dwelling older men was inconclusive. To examine the association of serum testosterone and estradiol concentrations with cognitive function in older men with or without vascular risk factors (VRFs). METHODS: This cross-sectional study consisted of 224 community-dwelling men aged 65-90 years in the Songjiang District of Shanghai, China. Serum testosterone and estradiol were measured by electrochemiluminescence immunoassay. The following five factors were defined as VRFs in this study: obesity, history of hypertension, diabetes, stroke, and coronary heart disease. Multivariable linear regression was used to examine the association of testosterone and estradiol with the Mini-Mental State Examination (MMSE) in participants with or without VRF. Restricted cubic spline (RCS) regression was performed to account for the nonlinearity of these associations. RESULTS: An inverted "U" shaped non-linear relationship was found between testosterone concentration and MMSE score in men with one VRF (P overall =.003, non-linear P =.002). Estradiol showed an inverted "U" shaped non-linear relationship with MMSE score independent of VRFs (men without VRF, P overall =.049, non-linear P =.015; men with one VRF, overall P =.007, non-linear P =.003; men with two or more VRFs, overall P =.009, non-linear P =.005). CONCLUSION: In older men, an optimal level of sex steroid concentration may be beneficial to cognitive function and the VRFs should be considered when interpreting the relationship between sex steroid and cognitive function.
Assuntos
Cognição , Estradiol , Hormônios Esteroides Gonadais , Idoso , Humanos , Masculino , China/epidemiologia , Estudos Transversais , Estradiol/sangue , Hormônios Esteroides Gonadais/sangue , Vida Independente , Fatores de Risco , TestosteronaRESUMO
BACKGROUND: Dose-response and nonlinear relationships of cigarette exposure with sleep disturbances and depression are warranted, and the potential mechanism of sex hormones in such associations remains unclear. METHODS: Cigarette exposure, trouble sleeping, and depression were assessed by standard questionnaires, and the levels of cotinine and sex steroid hormones were determined among 9900 adults from the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression, logistic regression, and mediation models were conducted to evaluate the associations between smoking, sex steroid hormones, trouble sleeping, and depression. RESULTS: With never smokers as a reference, current smokers had a higher prevalence of trouble sleeping (OR = 1.931, 95% CI: 1.680, 2.219) and depression (OR = 2.525, 95% CI: 1.936, 3.293) as well as testosterone level (ß = 0.083, 95% CI: 0.028, 0.140). Pack-years of smoking and cigarettes per day were positively associated with the prevalence of trouble sleeping and depression as well as testosterone level (Ptrend <0.05). The restricted cubic spline model showed linear relationships of cotinine with trouble sleeping, depression, and testosterone. The positive associations of cigarettes per day with trouble sleeping and depression were greater in females than that in males (Pmodification <0.05). However, the potential role of sex hormones was not observed in the association of cotinine with trouble sleeping or depression (Pmediation >0.05). CONCLUSION: Smoking may induce sex hormone disturbance and increase the risk of sleep problems and depression symptoms, and ceasing smoking may reduce the risk of such complications.
Assuntos
Cotinina , Depressão , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Estudos Transversais , Adulto , Depressão/epidemiologia , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Cotinina/sangue , Cotinina/análise , Transtornos do Sono-Vigília/epidemiologia , Fumar/epidemiologia , Prevalência , Hormônios Esteroides Gonadais/sangue , Adulto Jovem , Testosterona/sangue , IdosoRESUMO
Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6-19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E2 (TT/E2) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E2 in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E2, FAI, and TT (p trend <0.05) was observed in female adolescents for the highest quartile of urinary glyphosate compared to the lowest quartile. However, no similar association was observed among male adolescents. Our findings suggest that exposure to glyphosate at the current level may decrease the levels of sex steroids in adolescents, particularly female adolescents. Considering the cross-sectional study design, further research is needed to confirm our findings.
Assuntos
Glifosato , Hormônios Esteroides Gonadais , Criança , Humanos , Masculino , Adolescente , Feminino , Adulto Jovem , Adulto , Inquéritos Nutricionais , Estudos Transversais , Testosterona , Estradiol , Globulina de Ligação a Hormônio Sexual/metabolismoRESUMO
The objective of the present study was to investigate the association among the largest follicle (LF), preovulatory estradiol (E2), and predominant vaginal epithelial cell at the completion of hormonal ovarian stimulation for fixed-time artificial insemination (FTAI) in goats. Thirty-seven crossbred Boer does received gonadotropin-releasing hormone (GnRH) and intravaginal progesterone (P4)-releasing devices (day 0). On day 5, P4 devices were removed and does received prostaglandin F2α and equine chorionic gonadotrophin. On day 7, does received GnRH, and FTAI was undertaken. On day 7, does were divided into three groups, i.e. small-sized (3-3.9 mm; n = 5), medium-sized (4-4.9 mm; n = 8), and large-sized (≥5 mm; n = 24) according to the diameter of the ovarian LF; follicular characteristics (number and diameter) were identified, and blood samples and vaginal smears were collected. The average diameters of total antral follicles and LF and the percentage of superficial cell were greatest in large-sized LF does (p < .01). The average diameters of total antral follicle (r = .68) and LF (r = .71), number of preovulatory follicle (r = .58), and plasma E2 concentrations (r = .61) were positively correlated with the percentage of superficial cells (p < .01). The likelihood of a pregnancy outcome after the FTAI increased by 13.71 times in does with a greater average diameter of antral follicle, 14.18 times with emergence of a large preovulatory follicle, and 36.83 times with a higher percentage of vaginal superficial cells (p < .01). It was concluded that there is a relationship between the cell types of the vaginal epithelium, the diameters of the largest ovarian follicles, and the concentration of E2 in goats subjected to FTAI protocols.
Assuntos
Células Epiteliais , Estradiol , Cabras , Inseminação Artificial , Folículo Ovariano , Indução da Ovulação , Progesterona , Vagina , Animais , Feminino , Cabras/fisiologia , Estradiol/sangue , Folículo Ovariano/efeitos dos fármacos , Inseminação Artificial/veterinária , Células Epiteliais/efeitos dos fármacos , Progesterona/sangue , Gravidez , Indução da Ovulação/veterinária , Indução da Ovulação/métodos , Hormônio Liberador de Gonadotropina/farmacologia , Gonadotropina Coriônica/farmacologia , Gonadotropina Coriônica/administração & dosagem , Dinoprosta/farmacologia , Dinoprosta/administração & dosagem , Administração IntravaginalRESUMO
BACKGROUND: Ovarian development is an important prerequisite and basis for animal reproduction. In many vertebrates, it is regulated by multiple genes and influenced by sex steroid hormones and environmental factors. However, relative information is limited in shellfish. To explore the biological functions and molecular mechanisms of mRNA and non-coding RNA that regulate ovarian development in Scapharca broughtonii, we performed whole transcriptome sequencing analysis on ovaries at three developmental stages. Furthermore, the biological processes involved in the differential expression of mRNA and ncRNA were analyzed. RESULTS: A total of 11,342 mRNAs, 6897 lncRNAs, 135 circRNAs, and 275 miRNAs were differentially expressed. By mapping the differentially expressed RNAs from the three developmental stages of Venn diagram, multiple groups of shared mRNAs and lncRNAs were found to be associated with ovarian development, with some mRNA and ncRNA functions associated with steroid hormone. In addition, we constructed and visualized the lncRNA/circRNA-miRNA-mRNA network based on ceRNA targeting relationships. CONCLUSIONS: These findings may facilitate our further understanding the mRNA and ncRNAs roles in the regulation of shellfish reproduction.
Assuntos
Arcidae , MicroRNAs , RNA Longo não Codificante , Scapharca , Animais , Feminino , RNA Mensageiro/genética , RNA Longo não Codificante/genética , Ovário , RNA não Traduzido/genética , MicroRNAs/genética , RNA CircularRESUMO
Reproductive behaviors are sexually differentiated: for example, male rodents show mounting behavior, while females in estrus show lordosis behavior as sex-specific sexual behaviors. Kisspeptin neurons govern reproductive function via direct stimulation of gonadotropin-releasing hormone (GnRH) and subsequent gonadotropin release for gonadal steroidogenesis in mammals. First, we discuss the role of hypothalamic kisspeptin neurons as an indispensable regulator of sexual behavior by stimulating the synthesis of gonadal steroids, which exert "activational effects" on the behavior in adulthood. Second, we discuss the central role of kisspeptin neurons that are directly involved in neural circuits controlling sexual behavior in adulthood. We then focused on the role of perinatal hypothalamic kisspeptin neurons in the induction of perinatal testosterone secretion for its "organizational effects" on masculinization/defeminization of the male brain in rodents during a critical period. We subsequently concluded that kisspeptin neurons are key players in bridging the endocrine system and sexual behavior in mammals.
Assuntos
Hormônio Liberador de Gonadotropina , Kisspeptinas , Animais , Sistema Endócrino , Feminino , Masculino , Mamíferos , Neurônios , Gravidez , Receptores de Kisspeptina-1RESUMO
Duncan et al. reviewed the response to growth hormone stimulation testing after priming in peripubertal children. The concern is that there is little research documenting the response to growth hormone treatment in patients with sex hormone primed growth hormone stimulation testing and those unprimed. The controversy about priming or not can be summarized as follows: if one wants to know if the production of growth hormone during puberty will be adequate in terms of peak growth hormone responses then stimulation with priming should be done.
Assuntos
Hormônio do Crescimento , Hormônio do Crescimento Humano , Humanos , Criança , Adolescente , Hormônio do Crescimento/farmacologia , Hormônio do Crescimento Humano/farmacologia , Hormônios Esteroides Gonadais , Puberdade/fisiologia , Esteroides , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/tratamento farmacológico , Estatura/fisiologiaRESUMO
OBJECTIVE: Growth hormone stimulation testing (GHST) is used to diagnose growth hormone deficiency (GHD) in children. As sex steroids impact on anterior pituitary function, there is concern around the efficacy of GHST in peripubertal children, where endogenous sex steroid levels are low. Sex steroid priming before GHST is thought to improve test efficacy in these children, however evidence to support its use in clinical practice is limited. In this systematic review, we addressed the following research questions: Does priming increase GH stimulation test efficacy in peripubertal children? Does priming identify those who would benefit most from treatment in terms of final height? Is there evidence for an optimal sex-steroid priming regimen? DESIGN, PATIENTS, MEASUREMENTS: The study was registered with PROSPERO and conducted according to PRISMA guidelines. We searched Medline, Cochrane-Library, Scopus, EMBASE and Web-of-Science and included all studies that included GHST in both primed and unprimed children. A GH cut-off of 7 µg/L was used as a threshold for GHD. Study quality was assessed using the Risk-Of-Bias in Non- Randomized Studies (ROBINS-I) tool or the revised Cochrane risk-of-bias tool for Randomised trials. RESULTS: Fifteen studies met our inclusion criteria, of which 4/15 (27%) were randomised control trials. The majority (9/15) of the studies indicated that priming increases growth hormone response upon GHST in peripubertal children, increasing test specificity. Two studies investigated final height after treatment based on the results of primed versus unprimed GHST. These results indicate that growth hormone treatment based on results of a primed GHST improve outcomes compared with treatment based on an unprimed test. CONCLUSION: Sex-steroid priming increases the growth hormone response during GHST, resulting in fewer patients meeting the threshold required for a diagnosis of GHD. Unnecessary GH treatment may be avoided in some patients without a detrimental effect on final height. Numerous sex-steroid priming regimens have been used in clinical practice and the majority appear to be effective, but an optimal regimen has not been determined.
Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Humanos , Criança , Adolescente , Hormônio do Crescimento/uso terapêutico , Hormônios Esteroides Gonadais , Nanismo Hipofisário/tratamento farmacológico , Transtornos do Crescimento/tratamento farmacológico , Estatura , Esteroides/uso terapêuticoRESUMO
BACKGROUND: Ovarian advanced glycation end-products (AGEs) accumulation is associated with ovarian granulosa cells (GCs) dysfunction. Vitamin B6 derivatives positively affected reproduction. The current study was conducted to elucidate the AGEs effects on human luteinized mural GCs steroidogenesis in the presence or absence of pyridoxamine (PM). METHODS AND RESULTS: Isolated GCs of 50 healthy women were divided into four parts and treated with media alone (Control), PM alone, or human glycated albumin (HGA) with/without PM. Main steroidogenic enzymes and hormones were assessed by qRT-PCR and ELISA. The AGE receptor (RAGE) protein was also determined using Western blotting. The non-toxic concentration of HGA increased the expression of RAGE, StAR, 3ß-HSD, and 17ß-HSD (P < 0.0001 for all) but decreased the expression of CYP19A1 at mRNA levels. The increased RAGE protein expression was also confirmed by western blot analysis. These effects resulted in declined estradiol (E2), slightly, and a sharp rise in progesterone (P4) and testosterone (T) levels, respectively. PM, on its own, ameliorated the HGA-altered enzyme expression and, thereby, corrected the aberrant levels of E2, P4, and T. These effects are likely mediated by regulating the RAGE gene and protein expression. CONCLUSION: This study indicates that hormonal dysfunctions induced by the AGEs-RAGE axis in luteinized GCs are likely rectified by PM treatment. This effect is likely acquired by reduced expression of RAGE. A better understanding of how AGEs and PM interact in ovarian physiology and pathology may lead to more targeted therapy for treating ovarian dysfunction.
Assuntos
Reação de Maillard , Piridoxamina , Humanos , Feminino , Piridoxamina/farmacologia , Vitamina B 6 , Células da Granulosa , Produtos Finais de Glicação AvançadaRESUMO
We developed a microplate enzyme immunoassay (EIA) to measure dehydroepiandrosterone sulfate (DHEAS) in the blood, urine, and feces of Japanese macaques and evaluated the relationship between serum DHEAS and excreta DHEAS. Our DHEAS EIA using heterological DHEA derivatives conjugated with enzyme was highly sensitive, and linearities and recoveries for all matrices of Japanese macaques were reliable. For the biological evaluation of the metabolism of DHEAS in Japanese macaques, dissolved DHEAS was injected into the subjects, and consecutively collected serum, urine, and fecal samples were analyzed. The peaks of serum DHEAS were observed 6 h after the administration, while those of urine and feces were observed after 24 h. The fluctuation of those in urine and feces were significantly correlated with serum DHEAS levels. In addition, we measured pregnanediol-glucuronide (PdG), and estrone-conjugate (E1C) in urine and fecal samples to investigate the effects of administrated DHEAS on these progesterone and estrogen metabolites. The peak of PdG was observed 24 h after administration, then declined sharply. The concentration of E1C increased 1 week after administration in two out of three subjects. Our results suggest that measuring urinary and fecal DHEAS with our EIA provides a non-invasive alternative to assessing DHEAS levels in the serum of Japanese macaques.
Assuntos
Macaca fuscata , Progesterona , Animais , Macaca fuscata/metabolismo , Sulfato de Desidroepiandrosterona , Estrogênios , Estrona , DesidroepiandrosteronaRESUMO
The alligator snapping turtle (Macrochelys temminckii) is a species for which captive propagation and reintroduction programs are well established; however, little is known about its reproductive behavior and physiology. In this study, we measured monthly plasma sex steroid hormone concentrations of androgen (T + DHT) estradiol-17B (E2), and progesterone (P4), and used ultrasonography to monitor annual reproductive cycles of a captive population of alligator snapping turtles that is maintained under semi-natural conditions in southeastern Oklahoma. Concurrently, we used automated radio telemetry to measure the relative activity levels of male and female alligator snapping turtles and examine these activity patterns in the context of their reproductive cycles. We also measured monthly concentrations of the glucocorticoid (GC) corticosterone (CORT). Seasonal variation was only detected for T in males, but was observed for T, E2, and P4 in females. Vitellogenesis began in August and ended in April and coincided with elevated E2. Ovulation took place 10-29 April and the nesting period lasted from 11 May - 3 June. Males exhibited greater relative activity levels than females in the fall, winter, and early spring, which coincided with the period when mature sperm would be available for mating. Females were more active than males during the peri-nesting period in the spring. Seasonal changes in CORT were detected and did not differ between males and females. CORT concentrations were elevated in the late spring and summer, coincident with the foraging season, and depressed in the fall, and winter, and at their nadir in the early spring.
Assuntos
Jacarés e Crocodilos , Tartarugas , Animais , Masculino , Feminino , Sêmen , Hormônios Esteroides Gonadais , Progesterona , Corticosterona , Reprodução/fisiologia , Estações do AnoRESUMO
Transgender medicine is a growing clinical field. Hormone therapy (testosterone or estrogen treatment) is part of the standard of gender-affirming medical care, yet clinical pharmacological knowledge in transgender medicine is lacking. Herein, we summarize available clinical and pharmacologic data for hormone therapy among transgender and gender diverse people.
RESUMO
BACKGROUND: Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. METHODS: The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children's Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. RESULTS: After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36-0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01-4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. CONCLUSIONS: The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children.