Pheochromocytomas (PCCs) are tumors arising from chromaffin cells in the adrenal medulla, and paragangliomas (PGLs) are tumors derived from extra-adrenal sympathetic or parasympathetic paraganglia; these tumors are collectively referred to as PPGL cancer. Treatment for PPGL primarily involves surgical removal of the tumor, and only limited options are available for treatment of the disease once it becomes metastatic. Human carriers of the heterozygous mutations in the succinate dehydrogenase subunit B () gene are susceptible to the development of PPGL.
View Article and Find Full Text PDFBest Pract Res Clin Endocrinol Metab
December 2024
The complexity of omes - the key cellular ensembles (genome and epigenome, transcriptome, proteome, and metabolome) - is becoming increasingly understood in terms of big-data analysis, the omics. Amongst these, proteomics provides a global description of quantitative and qualitative alterations of protein expression (or protein abundance in body fluids) in response to physiologic or pathologic processes while metabolomics offers a functional portrait of the physiological state by quantifying metabolite abundances in biological samples. Here, we summarize how different techniques of proteomic and metabolic analysis can be used to define key biochemical characteristics of pheochromocytomas/paragangliomas (PPGL).
View Article and Find Full Text PDFBackground: Prenatal nicotine exposure (PNE) has been documented to cause numerous deleterious effects on fetal development. However, the epigenetic changes promoted by nicotine exposure on germ cells are still not well understood.
Objectives: In this study, we focused on elucidating the impact of prenatal nicotine exposure on regulatory epigenetic mechanisms important for germ cell development.
GATA4 is a transcription factor known for its crucial role in the development of many tissues, including the liver; however, its role in adult liver metabolism is unknown. Here, using high-throughput sequencing technologies, we identified GATA4 as a transcriptional regulator of metabolism in the liver. GATA4 expression is elevated in response to refeeding, and its occupancy is increased at enhancers of genes linked to fatty acid and lipoprotein metabolism.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
November 2022
Genetic testing has become the standard of care for many disease states. As a result, physicians treating patients who have tumors often rely on germline genetic testing results for making clinical decisions. Cases of two sisters carrying a germline variant are highlighted whereby possible other genetic drivers were discovered on tumor analysis (also referred to as CHK2) loss of function has been firmly associated with breast cancer development.
View Article and Find Full Text PDFBrown adipose tissue (BAT) generates heat through non-shivering thermogenesis, and increasing BAT amounts or activity could facilitate obesity treatment and provide metabolic benefits. In mice, BAT has been reported in perirenal, thoracic and cranial sites. Here, we describe new pelvic and lower abdominal BAT depots located around the urethra, internal reproductive and urinary tract organs and major lower pelvic blood vessels, as well as between adjacent muscles where the upper hind leg meets the abdominal cavity.
View Article and Find Full Text PDFTobacco smoking is the leading cause of preventable death. Numerous reports link smoking in pregnancy with serious adverse outcomes, such as miscarriage, stillbirth, prematurity, low birth weight, perinatal morbidity, and infant mortality. Corollaries of consuming nicotine in pregnancy, separate from smoking, are less explored, and the mechanisms of nicotine action on maternal-fetal communication are poorly understood.
View Article and Find Full Text PDFBackground: Neonicotinoids, a widely used class of insecticide, have attracted much attention because of their widespread use that has resulted in the decline of the bee population. Accumulating evidence suggests potential animal and human exposure to neonicotinoids, which is a cause of public concern.
Objectives: In this study, we examined the effects of a neonicotinoid, , on the male reproductive system.
Background: Chlordecone (CD), also known as Kepone, is an organochlorine insecticide that has been used in banana crops in the French West Indies. Due to long-term contamination of soils and water, the population is still exposed to CD. Exposure to CD in adulthood is associated with an increased risk of prostate cancer (PCa).
View Article and Find Full Text PDFJ Investig Med High Impact Case Rep
June 2021
To characterize the expression of steroidogenic enzymes implicated in the development of ovarian steroid cell tumors, not otherwise specified (SCT-NOS). We present 4 ovarian SCT-NOS evaluated by immunohistochemical staining of steroidogenic enzymes as an approach to define this entity pathologically. All 4 ovarian SCT-NOS showed increased expression for cholesterol side-chain cleavage enzyme (CYP11A1), 17α-hydroxylase (CYP17A1), 17β-hydroxysteroid dehydrogenase 1 (HSD17B1), aldo-ketoreductase type 1 C3 (AKR1C3), 3β-hydroxysteroid dehydrogenase 2 (HSD3B2), 5α-reductase type 2 (SRD5A2), steroid sulfatase (SULT2A1), estrogen sulfotransferase (EST), and aromatase (CYP19A1).
View Article and Find Full Text PDFBackground: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors that are mostly benign. Metastatic disease does occur in about 10% of cases of PCC and up to 25% of PGL, and for these patients no effective therapies are available. Patients with mutations in the succinate dehydrogenase subunit B (SDHB) gene tend to have metastatic disease.
View Article and Find Full Text PDFPrimary aldosteronism (PA) results from excess production of mineralocorticoid hormone aldosterone by the adrenal cortex. It is normally caused either by unilateral aldosterone-producing adenoma (APA) or by bilateral aldosterone excess as a result of bilateral adrenal hyperplasia. PA is the most common cause of secondary hypertension and associated morbidity and mortality.
View Article and Find Full Text PDFEnhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that suppresses gene expression. Previously, we developed a conditional null model where EZH2 is knocked out in uterus. Deletion of uterine EZH2 increased proliferation of luminal and glandular epithelial cells.
View Article and Find Full Text PDFGenetic studies traditionally focus on DNA as the molecule that passes information on from parents to their offspring. Changes in the DNA code alter heritable information and can more or less severely affect the progeny's phenotype. While the idea that information can be inherited between generations independently of the DNA's nucleotide sequence is not new, the outcome of recent studies provides a mechanistic foundation for the concept.
View Article and Find Full Text PDFPheochromocytomas are rare neuroendocrine tumors. Extra-adrenal lesions arising from the autonomic neural ganglia are termed paraganglioma. Clinical symptoms are common between the adrenal and extra-adrenal forms and are determined by excess secretion of catecholamines.
View Article and Find Full Text PDFChlordecone (CD) is an insecticide that was used in the French West Indies for several years to control the banana root borer pest. Given its nonsignificant degradation, it persists in the environment. CD is a carcinogenic compound with reproductive and developmental toxicity and is a recognized endocrine-disrupting chemical.
View Article and Find Full Text PDFEnvironmental factors can affect epigenetic events during germline reprogramming and impose distinctive transgenerational consequences onto the offspring. In this study, we examined the transgenerational effects of chlordecone (CD), an organochlorine insecticide with well-known estrogenic properties. We exposed pregnant mice to CD from embryonic day 6.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
May 2018
Context: Pheochromocytomas (PCCs) are tumors that are derived from the chromaffin cells of the adrenal medulla. Extra-adrenal PCCs called paragangliomas (PGLs) are derived from the sympathetic and parasympathetic chain ganglia. PCCs secrete catecholamines, which cause hypertension and have adverse cardiovascular consequences as a result of catecholamine excess.
View Article and Find Full Text PDFThe widely-used herbicide atrazine (ATZ) is detected in ground and surface water in many countries. Several studies in animals have demonstrated that ATZ has endocrine-disrupting effects on male and female reproduction in many vertebrate species. In this study, we investigated the effects of ATZ exposure on meiosis, a key step in gametogenesis in mammals.
View Article and Find Full Text PDFSteroid hormones, acting through their cognate nuclear receptors, are critical for many reproductive and non-reproductive functions. Over the past two decades, it has become increasingly clear that in addition to cytoplasmic/nuclear steroid receptors that alter gene transcription when liganded, a small fraction of cellular steroid receptors are localized to the cell membranes, where they mediate rapid steroid hormone effects. 17β-Estradiol (E2), a key steroid hormone for both male and female reproduction, acts predominately through its main receptor, estrogen receptor 1 (ESR1).
View Article and Find Full Text PDFThe epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females.
View Article and Find Full Text PDFThe adrenal glands consist of an outer cortex and an inner medulla, and their primary purposes include hormone synthesis and secretion. The adrenal cortex produces a complex array of steroid hormones, whereas the medulla is part of the sympathetic nervous system and produces the catecholamines epinephrine and norepinephrine. In the mouse, GATA binding protein (GATA) 4 and GATA6 transcription factors are coexpressed in several embryonic tissues, including the adrenal cortex.
View Article and Find Full Text PDFThe roles of the GATA4 and GATA6 transcription factors in testis development were examined by simultaneously ablating Gata4 and Gata6 with Sf1Cre (Nr5a1Cre). The deletion of both genes resulted in a striking testicular phenotype. Embryonic Sf1Cre; Gata4(flox/flox) Gata6(flox/flox) (conditional double mutant) testes were smaller than control organs and contained irregular testis cords and fewer gonocytes.
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