Current Opinion in Endocrine and Metabolic Research最新文献

As energy depots in many circumstances have been limited during evolution, it is necessary to prioritize how to manage energy resources. In this review we summarize data from the last 15 years indicating that osteoblast-lineage cells are regulators of whole-body energy metabolism and fat mass. We focus mainly on three factors, osteocalcin, lipocalin-2 and sclerostin, that are released by osteoblast-lineage cells and proposed to exert endocrine effects on metabolism. In addition, we present a hypothesis on why osteoblast-lineage cells during evolution have developed a function to regulate metabolism and fat mass. We propose that osteoblast-lineage cells through the osteocyte network in bone are sensors of gravitational forces induced by body mass and gravity on land-living species. By sensing the body weight, the osteoblastlineage cells may then feed-back this information on the whole-body nutritional status via osteoblast-derived endocrine factors or via the nervous system to regulate energy metabolism and fat mass.

There is increasing evidence from animal models that bone, in addition to its traditional function of providing structural support for the organism, has a rich network of interactions with multiple other tissues. This perspective focuses on evidence from human studies demonstrating that bone is an endocrine organ regulating energy metabolism, with the specific examples being osteocalcin, lipocalin 2, RANKL, and sclerostin. Conversely, animal studies have also demonstrated that a key hormone regulating energy metabolism, leptin, regulates bone metabolism via the sympathetic nervous system. Studies in humans have established a role for the sympathetic nervous system in regulating bone turnover; indeed, the potential therapeutic benefit of targeting this pathway in humans to prevent postmenopausal bone loss is currently being evaluated.

Depression and anxiety are amongst the most prevalent and disabling conditions worldwide, imposing significant burden to individuals, families, and their communities. It is now known that both conditions affect females more often than males, and that some can be particularly more vulnerable to symptoms (new, recurrent) during reproductive-related windows of vulnerability, including the menopause transition and early postmenopausal years.

As estrogen exerts neuro-modulatory effects on mood, cognition, and behaviour through monoaminergic systems (e.g., 5-HT, NE), rapid fluctuations of estradiol (E2) levels seem to be associated with heightened risk for/emergency of anxiety and depression during midlife years, along with other menopause-associated complaints such as vasomotor symptoms and sleep disturbances.

Psychopharmacologic and behavioural interventions remain the first-line treatment for depression and anxiety across the life span; however, estrogen-based therapies, particularly transdermal estradiol, should be considered as part of the treatment armamentarium for symptomatic, midlife women.

Early-stage thyroid cancer is about 4 times more common in women than men, but the underlying subclinical prevalence is the same between the two sexes. As the lethality of the cancer type increases, the ratio in incidence for women compared to men approaches 1:1. These facts suggest that differences in healthcare utilization may be a major reason thyroid cancer is diagnosed more in women than men. Physiological elements could also contribute, as women have a higher prevalence of thyroid nodularity compared to men. Current research suggests estrogen does not play a major role, but genetics may be a potential reason for increased rates of thyroid cancer in women compared to men. Immune surveillance is greater in women and currently is thought to be protective against thyroid cancer development. This review summarizes recent evidence examining the role of these factors in modulating the sex-disparity observed in thyroid cancer incidence.

Thyroid cancers are often initiated by the acquisition of a BRAF^V600E mutation. BRAF^V600E-driven thyroid tumors display a wide range of behaviors, from the slow-growing papillary carcinomas to the highly aggressive anaplastic. Mutations in the promoter of TERT (telomerase reverse transcriptase) gene were discovered a decade ago and identified as prevalent events in thyroid cancers. Multiple studies showed that TERT promoter mutations, particularly when co-occurring with BRAF^V600E, are markers of poor prognosis across thyroid cancer subtypes, and can be implemented for routine clinical stratification. Mechanistically, TERT promoter mutations reactivate telomerase expression via the differential recruitment of transcriptional complexes. Re-expression of TERT impacts tumor biology, plausibly via both the well-known function of telomerase maintaining telomeres and by affecting other cancer-relevant processes.

Hot flashes and night sweats, also known as vasomotor symptoms (VMS), are common and bothersome symptoms of the menopause transition. In addition to negatively impacting quality of life, VMS have been associated with multiple indicators of cardiovascular disease (CVD) risk, including an unfavorable CVD risk factor profile, increased subclinical CVD, and elevated risk of CVD events. Several facets of VMS have been associated with CVD risk, including the frequency, timing, duration, and severity of VMS. VMS may signify poor or degrading cardiovascular health among midlife women and indicate women who warrant focused CVD prevention efforts.

Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal types of cancer and treatment options remain very limited. The majority of patients present initially with metastatic disease and require systemic therapy. The shift from conventional cytotoxic therapies to more specific, molecularly targeted therapies is a rapidly developing phenomenon. Despite the recent success of BRAF-directed therapies, druggable mutations in ATC remain scarce and disappointing. Translational research in this area is key to unlocking therapeutic options in ATC, especially as molecular testing becomes increasingly routine. Increasing number of studies in the last decade have described the genomic alterations of ATC, vastly improving our understanding of its development and evolution. In this review, we provide a snapshot of the key DNA sequencing studies of ATC and their potential applications in emerging targeted therapies. We also highlight the future directions of research to tackle this devastating diagnosis.