Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Cushing Syndrome I: Introduction01:26

Cushing Syndrome I: Introduction

Cushing syndrome refers to the collection of clinical manifestations that arise when tissues are exposed to excessive amounts of cortisol or cortisol-like medications over an extended period. Cortisol, a glucocorticoid produced by the adrenal cortex, regulates metabolism, immune responses, and the body’s adaptation to stress. When its concentration remains chronically elevated, these physiological pathways become dysregulated, resulting in the characteristic features of the syndrome.Exogenous...
Cushing Syndrome II: Pathophysiology01:19

Cushing Syndrome II: Pathophysiology

Cortisol production is normally governed by the hypothalamic–pituitary–adrenal (HPA) axis, which maintains hormonal balance through tightly regulated feedback mechanisms. Disruption of this regulatory system is central to the development of Cushing syndrome, whether the excess cortisol originates from external medications or internal pathology. Persistent cortisol elevation alters metabolism, immune function, and endocrine signaling, producing the characteristic clinical features of the...
Adrenal Gland Disorders01:27

Adrenal Gland Disorders

Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2 (COX-2),...
Hypoglycemia and Glucagon01:15

Hypoglycemia and Glucagon

Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Extension of the Phase 3 Trial of Somatrogon in Children with Growth Hormone Deficiency: 3 Years of Safety and Efficacy.

Hormone research in paediatrics·2026
Same author

Correction: A real-time PCR assay for detection of low <i>Pneumocystis jirovecii</i> levels.

Frontiers in microbiology·2026
Same author

Microplastics in Female Reproductive and Pregnancy Organs: A Systematic Review.

Life (Basel, Switzerland)·2026
Same author

Artificial and natural non-nutritive sweeteners drive divergent gut and genetic responses across generations.

Frontiers in nutrition·2026
Same author

Increased Intrahepatic Mast Cell Density in Liver Cirrhosis Due to MASLD and Other Non-Infectious Chronic Liver Diseases.

International journal of molecular sciences·2026
Same author

Significant Response to Denosumab Yet with Severe Rebound Hypercalcemia in a 9-Year-Old Boy with Aneurysmal Bone Cyst: A Case Report.

Children (Basel, Switzerland)·2025
Same journal

The Extra X Chromosome and Autoimmune Susceptibility in Klinefelter Syndrome.

The Journal of clinical endocrinology and metabolism·2026
Same journal

Pathophysiology-Based Classification of Male Infertility: Evidence from an 800-patient Prospective Cohort.

The Journal of clinical endocrinology and metabolism·2026
Same journal

Parathyroid Carcinoma: From Molecular Pathogenesis to Multidisciplinary Management.

The Journal of clinical endocrinology and metabolism·2026
Same journal

Genetic and Clinical Factors Associated With Metformin Plasma Concentrations Following an Acute Metformin Challenge.

The Journal of clinical endocrinology and metabolism·2026
Same journal

Continuous glucose monitoring-derived time in range is associated with changes in arterial stiffness in type 2 diabetes.

The Journal of clinical endocrinology and metabolism·2026
Same journal

Association of the Primary Aldosteronism Severity Classification with Lateralization and Treatment Outcomes.

The Journal of clinical endocrinology and metabolism·2026
See all related articles

Related Experiment Video

Updated: May 15, 2026

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids
08:02

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids

Published on: April 25, 2016

Bioinactive ACTH causing glucocorticoid deficiency.

Mark E Samuels1, Nicole Gallo-Payet, Sandra Pinard

  • 1Endocrinology Service and Research Center, Centre Hospitalier Universitaire Sainte-Justine, Department of Pediatrics, University of Montreal, Montreal H3T 1C5, Canada.

The Journal of Clinical Endocrinology and Metabolism
|January 8, 2013
PubMed
Summary
This summary is machine-generated.

Two children with adrenal insufficiency had inactive ACTH due to POMC mutations. Genetic testing identified a novel mutation, highlighting limitations of immunoassays and guiding treatment decisions.

More Related Videos

Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions
04:33

Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions

Published on: March 12, 2019

Biochemical Reconstitution of Steroid Receptor&#x2022;Hsp90 Protein Complexes and Reactivation of Ligand Binding
11:07

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding

Published on: September 21, 2011

Related Experiment Videos

Last Updated: May 15, 2026

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids
08:02

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids

Published on: April 25, 2016

Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions
04:33

Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions

Published on: March 12, 2019

Biochemical Reconstitution of Steroid Receptor&#x2022;Hsp90 Protein Complexes and Reactivation of Ligand Binding
11:07

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding

Published on: September 21, 2011

Area of Science:

  • Endocrinology
  • Genetics
  • Molecular Biology

Background:

  • Two pediatric patients presented with symptoms of primary adrenal insufficiency, including hypoglycemia and low cortisol with high ACTH levels.
  • Standard genetic testing for known ACTH resistance genes was negative.
  • Whole exome sequencing identified novel pro-opiomelanocortin (POMC) mutations in both patients.

Purpose of the Study:

  • To investigate the biological activity of a novel POMC mutation (p.R8C) identified in patients with apparent ACTH resistance.
  • To evaluate the diagnostic limitations of immunoassays in cases of biologically inactive but immunoreactive hormones.
  • To determine the clinical significance of POMC mutations in pediatric adrenal insufficiency.

Main Methods:

  • Whole exome sequencing and Sanger sequencing were employed for genetic analysis.
  • Peptide synthesis was performed to create mutant ACTH and alpha-MSH (α-MSH) peptides.
  • Hormone binding and cell-based activation assays using melanocortin receptors (MC2R, MC1R, MC4R) were conducted.

Main Results:

  • The synthesized ACTH-R8C mutant retained immunoreactivity but failed to bind or activate the melanocortin-2 receptor (MC2R).
  • The α-MSH-R8C mutant was also bioinactive, failing to stimulate cAMP production in MC1R and MC4R expressing cells.
  • These findings confirm the bioinactive nature of the novel POMC variants.

Conclusions:

  • The study reports the first cases of glucocorticoid deficiency caused by a biologically inactive but immunoreactive ACTH molecule due to POMC mutations.
  • POMC mutations should be considered in patients with apparent ACTH resistance, and genetic analysis is crucial for diagnosis.
  • The findings underscore the limitations of immunoassay diagnostics and the importance of genetic testing, leading to the cessation of unnecessary mineralocorticoid treatment in the affected patients.