- At the crossroads of fate - somatic cell lineage specification in the fetal gonad. [Journal Article]
- EREndocr Rev 2018 May 15
- The reproductive endocrine systems are vastly different between male and female. This sexual dimorphism of endocrine milieu originates from sex-specific differentiation of the somatic cells in the go...
The reproductive endocrine systems are vastly different between male and female. This sexual dimorphism of endocrine milieu originates from sex-specific differentiation of the somatic cells in the gonads during fetal life. The majority of gonadal somatic cells arise from the adrenogonadal primordium. After separation of the adrenal and gonadal primordia, the gonadal somatic cells initiate sex-specific differentiation during gonadal sex determination with the specification of the supporting cell lineages: Sertoli cells in the testis vs. granulosa cells in the ovary. The supporting cell lineages then facilitate the differentiation of the steroidogenic cell lineages, Leydig cells in the testis and theca cells in the ovary. Proper differentiation of these cell types defines the somatic cell environment that is essential for germ cell development, hormone production, and establishment of the reproductive tracts. Impairment of lineage specification and function of gonadal somatic cells can lead to disorders of sexual development (DSDs) in humans. Human DSDs and processes for gonadal development have been successfully modelled using genetically modified mouse models. In this review, we focus on the fate decision processes from the initial stage of formation of the adrenogonadal primordium in the embryo, to the maintenance of the somatic cell identities in the gonads when they become fully differentiated in adulthood.
- Metabolic flexibility as an adaptation to energy resources and requirements in health and disease. [Journal Article]
- EREndocr Rev 2018 Apr 24
- The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we...
The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways which is regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors like dietary composition and feeding frequency, exercise training, and use of pharmacological compounds influence metabolic flexibility and will be discussed here. Lastly, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.
- Pituitary Diseases and Bone. [Journal Article]
- EREndocr Rev 2018 Apr 19
- Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. Skeletal fragility associated with high risk o...
Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. Skeletal fragility associated with high risk of fractures is a common complication of several pituitary diseases such as hypopituitarism, Cushing disease, acromegaly and hyperprolactinemia. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity and fractures may occur even in the presence of normal or low-normal bone mineral density as measured by dual-energy X-ray absorptiometry, making difficult the prediction of fractures in these clinical settings. Treatment of pituitary hormone excess and deficiency generally improves skeletal health, although some patients remain at high risk of fractures and treatment with bone-active drugs may become mandatory.Aim of this review will be to discuss the physiological, pathophysiological and clinical insights of the bone involvement in pituitary diseases.
- Sex and Gender Differences Research Design for Basic, Clinical and Population Studies: Essentials for Investigators. [Journal Article]
- EREndocr Rev 2018 Apr 12
- A sex and gender-informed perspective increases rigor, promotes discovery, and expands the relevance of biomedical research. In the current era of accountability to present data for males and females...
A sex and gender-informed perspective increases rigor, promotes discovery, and expands the relevance of biomedical research. In the current era of accountability to present data for males and females, thoughtful and deliberate methodology can improve study design and inference in sex and gender differences research. We address issues of motivation, subject selection, sample size, data collection, analysis, and interpretation, considering implications for basic, clinical, and population research. In particular, we focus on methods to test sex/gender differences as effect modification or interaction, and discuss why some inferences from sex-stratified data should be viewed with caution. Without careful methodology, the pursuit of sex difference research, despite a mandate from funding agencies, will result in a literature of contradiction. However, given the historic lack of attention to sex differences, the absence of evidence for sex differences is not necessarily evidence of the absence of sex differences. Thoughtfully conceived and conducted sex and gender differences research is needed to drive scientific and therapeutic discovery for all sexes and genders.
- Erratum. [Journal Article]
- EREndocr Rev 2018 Mar 23
- ERRATUM FOR "Ovarian Follicular Theca Cell Recruitment, Differentiation, and Impact on Fertility: 2017 Update". [Journal Article]
- EREndocr Rev 2018 Mar 08
- Lessons from the Testosterone Trials. [Journal Article]
- EREndocr Rev 2018 Mar 07
- The Testosterone Trials (TTrials) were a coordinated set of seven, placebo-controlled, double blind trials in 788 men of mean age 72 years to determine the efficacy of increasing the testosterone lev...
The Testosterone Trials (TTrials) were a coordinated set of seven, placebo-controlled, double blind trials in 788 men of mean age 72 years to determine the efficacy of increasing the testosterone levels of older men with low testosterone. Testosterone treatment increased the median testosterone level from unequivocally low at baseline to midnormal for young men after three months and maintained that level until month 12. In the Sexual Function Trial, testosterone increased sexual activity, sexual desire and erectile function. In the Physical Function Trial, testosterone did not increase the distance walked in 6 minutes in men whose walk speed was slow, but in all TTrials participants, testosterone did increase the distance walked. In the Vitality Trial, testosterone did not increase energy but slightly improved mood and depressive symptoms. In the Cognitive Function Trial, testosterone did not improve cognitive function. In the Anemia Trial, testosterone increased hemoglobin in both men who had anemia of known cause as well as in men with unexplained anemia. In the Bone Trial, testosterone increased volumetric bone mineral density and estimated strength of the spine and hip. In the Cardiovascular Trial, testosterone increased coronary artery noncalcified plaque volume by computerized tomographic angiography. Although testosterone was not associated with more cardiovascular or prostate adverse events than placebo, a trial in a much larger number of men for a much longer period would be necessary to determine if testosterone increases cardiovascular or prostate risk.
- The Science of Obesity Management: An Endocrine Society Scientific Statement. [Journal Article]
- EREndocr Rev 2018 Apr 01; 39(2):79-132
- The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health implications. Genetic...
The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health implications. Genetic, environmental, and behavioral factors influence the development of obesity, and both the general public and health professionals stigmatize those who suffer from the disease. Obesity is associated with and contributes to a shortened life span, type 2 diabetes mellitus, cardiovascular disease, some cancers, kidney disease, obstructive sleep apnea, gout, osteoarthritis, and hepatobiliary disease, among others. Weight loss reduces all of these diseases in a dose-related manner-the more weight lost, the better the outcome. The phenotype of "medically healthy obesity" appears to be a transient state that progresses over time to an unhealthy phenotype, especially in children and adolescents. Weight loss is best achieved by reducing energy intake and increasing energy expenditure. Programs that are effective for weight loss include peer-reviewed and approved lifestyle modification programs, diets, commercial weight-loss programs, exercise programs, medications, and surgery. Over-the-counter herbal preparations that some patients use to treat obesity have limited, if any, data documenting their efficacy or safety, and there are few regulatory requirements. Weight regain is expected in all patients, especially when treatment is discontinued. When making treatment decisions, clinicians should consider body fat distribution and individual health risks in addition to body mass index.
- The circadian clock in white and brown adipose tissue: mechanistic, endocrine and clinical aspects. [Journal Article]
- EREndocr Rev 2018 Feb 27
- Obesity is a major risk factor for the development of illnesses, such as insulin resistance and hypertension and has become a serious public health problem. Mammals have developed a circadian clock l...
Obesity is a major risk factor for the development of illnesses, such as insulin resistance and hypertension and has become a serious public health problem. Mammals have developed a circadian clock located in the hypothalamic suprachiasmatic nuclei (SCN) that responds to the environmental light-dark cycle. Clocks similar to the one located in the SCN are found in peripheral tissues, such as the kidney, liver and adipose tissue. The circadian clock regulates metabolism and energy homeostasis in peripheral tissues by mediating activity and/or expression of key metabolic enzymes and transport systems. Knockouts or mutations in clock genes that lead to disruption of cellular rhythmicity have provided evidence to the tight link between the circadian clock and metabolism. In addition, key proteins play a dual role in regulating the core clock mechanism as well as adipose tissue metabolism and link circadian rhythms with lipogenesis and lipolysis. Adipose tissues are distinguished as white, brown and beige (or brite), each with unique metabolic characteristics. Recently, the role of the circadian clock in regulating the differentiation into the different adipose tissues has been investigated. In this review, the role of clock proteins and the downstream signaling pathways in white, brown and brite adipose tissue function and differentiation will be reviewed. In addition, chronodisruption and metabolic disorders and clinical aspects of circadian adiposity will be addressed.
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- Klinefelter syndrome - integrating genetics, neuropsychology and endocrinology. [Journal Article]
- EREndocr Rev 2018 Feb 09
- Although first identified over 70 years ago, Klinefelter syndrome (KS) continue to pose significant diagnostic challenges, as many patients are still misdiagnosed, or remain undiagnosed. In fact, as ...
Although first identified over 70 years ago, Klinefelter syndrome (KS) continue to pose significant diagnostic challenges, as many patients are still misdiagnosed, or remain undiagnosed. In fact, as few as 25% of KS patients are accurately diagnosed, and most of these diagnoses are not made until adulthood. Classic characteristics of KS include small testes, infertility, hypergonadothropic hypogonadism, and cognitive impairment. However, the pathophysiology behind KS is not well understood, although genetic effects are also thought to play a role. For example, recent developments in genetics and genomics point to a fundamental change in our understanding of KS, with global epigenetic and RNA expression changes playing a central role for the phenotype.KS is also associated with more general health markers, including higher morbidity and mortality rates, and lower socio-economic status (which likely affects both morbidity and mortality). In addition, hypogonadism is associated with greater risk of of metabolic syndrome, type 2 diabetes, cardiovascular disease, breast cancer, and extragonadal germ cell tumors. Medical treatment typically focuses on testosterone replacement therapy (TRT), although the effects of this therapy has not been studied rigorously, and future studies need to evaluate the effects of TRT on metabolic risk and neurocognitive outcomes.This review presents a comprehensive, interdisciplinary examination of recent developments in genetic, endocrine and neurocognitive science, including the study of animal models regarding KS. It also provides a number of recommendations for improving the effectiveness of research and clinical practice, including neonatal KS screening programs, and a multidisciplinary approach to KS treatment from childhood until senescence.