scholarly journals Sonic Hedgehog and WNT Signaling Promote Adrenal Gland Regeneration in Male Mice

Endocrinology ◽  
2017 ◽  
Vol 159 (2) ◽  
pp. 579-596 ◽  
Author(s):  
Isabella Finco ◽  
Antonio M Lerario ◽  
Gary D Hammer
Keyword(s):  
Wnt Signaling ◽  
Adrenal Cortex ◽  
Sonic Hedgehog ◽  
Molecular Mechanisms ◽  
Zona Glomerulosa ◽  
Glucocorticoid Therapy ◽  
Adrenocortical Function ◽  
Glucocorticoid Treatment ◽  
Major Health Problem

Abstract The atrophy and hypofunction of the adrenal cortex following long-term pharmacologic glucocorticoid therapy is a major health problem necessitating chronic glucocorticoid replacement that often prolongs the ultimate return of endogenous adrenocortical function. Underlying this functional recovery is anatomic regeneration, the cellular and molecular mechanisms of which are poorly understood. Investigating the lineage contribution of cortical Sonic hedgehog (Shh)+ progenitor cells and the SHH–responsive capsular Gli1+ cells to the regenerating adrenal cortex, we observed a spatially and temporally bimodal contribution of both cell types to adrenocortical regeneration following cessation of glucocorticoid treatment. First, an early repopulation of the cortex is defined by a marked delamination and expansion of capsular Gli1+ cells, recapitulating the establishment of the capsular-cortical homeostatic niche during embryonic development. This rapid repopulation is promptly cleared from the cortical compartment only to be supplanted by repopulating cortical cells derived from the resident long-term-retained zona glomerulosa Shh+ progenitors. Pharmacologic and genetic dissection of SHH signaling further defines an SHH-dependent activation of WNT signaling that supports regeneration of the cortex following long-term glucocorticoid therapy. We define the signaling and lineage relationships that underlie the regeneration process.

SOME ASPECTS OF ZONATION AND FUNCTION OF THE ADRENAL CORTEX

1954 ◽  
Vol 10 (3) ◽  
pp. 245-NP ◽  
Author(s):  
I. CHESTER JONES ◽  
C. C. ROBY
Keyword(s):  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Male Adult ◽  
Sodium Potassium ◽  
Potassium Intake ◽  
Adult Mice ◽  
Water Output ◽  
And Function ◽  
Sodium And Potassium

SUMMARY Male adult mice, 80 days after hypophysectomy, show approximately the same pattern of sodium and potassium intake and sodium, potassium and water output as normal mice. The healthy remnant of adrenal cortex left after the operation is thought to be responsible for the day-to-day competence of the hypophysectomized animal in salt-electrolyte metabolism. The histology of the cortex is described and it is shown that, with the injection of ACTH, a cortex of normal appearance can be regenerated from the persistent zona glomerulosa of the long-term hypophysectomized mouse.

scholarly journals P.089 Recovery from chronic secondary adrenal insufficiency in patients with pituitary disorders

2016 ◽  
Vol 43 (S2) ◽  
pp. S41-S41
Author(s):  
V Munro ◽  
B Tugwell ◽  
S Doucette ◽  
DB Clarke ◽  
A Lacroix ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Tumour Size ◽  
Pituitary Surgery ◽  
Complete Recovery ◽  
Glucocorticoid Therapy ◽  
Hormone Deficiency ◽  
Secondary Adrenal Insufficiency ◽  
Glucocorticoid Treatment ◽  
Acth Secreting

Background: Patients with pituitary disorders may be placed on steroid replacement for secondary adrenal insufficiency (SAI), generally after pituitary surgery; however, data regarding recovery of long-term SAI are lacking. We conducted a study to assess the longer term recovery rate of SAI in patients with pituitary disorders. Methods: We identified all SAI patients from prospectively entered data in the Halifax Neuropituitary Database from November 1, 2005 to September 30, 2014, who had required glucocorticoid therapy for >3 months, and a minimum follow-up of 6 months. Exclusion: ACTH-secreting adenomas; peri-operative glucocorticoid treatment only; glucocorticoids for non-pituitary conditions. Results: 55 patients fulfilled the criteria, 41 (75%) of which had transsphenoidal surgery. Nine (16.4%) patients had complete recovery of SAI over a median of 20 months (range: 8–51). Smaller tumour size and initial cortisol >175 nmol/L had increased likelihood of recovery; those with secondary hypogonadism or growth hormone deficiency were less likely to recover. Conclusions: This is the first study to examine long-term recover of SAI in patients with pituitary disorders: approximately 1 in 6 patients recover adrenal function, up to 5 years after diagnosis. Consequently, patients with SAI should undergo regular testing to prevent unnecessary chronic glucocorticoid therapy.

scholarly journals Wnt2b Is Essential for Adrenocortical Progenitor Cell Fate and Zona Glomerulosa Identity in Vivo

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A74-A75
Author(s):  
Donald W Little ◽  
Kleiton S Borges ◽  
Kaitlin J Basham ◽  
Amy E O’Connell ◽  
Christopher R LaPensee ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Adrenal Cortex ◽  
Progenitor Cell ◽  
Weight Ratio ◽  
Zona Glomerulosa ◽  
Conditional Knockout ◽  
Whole Body ◽  
Steroidogenic Cells

Abstract Dysregulation of normal adrenal structure and function contributes to a spectrum of diseases from hypoplasia to cancer. Peripheral adrenocortical progenitor cells in the zona glomerulosa (zG) centripetally migrate and differentiate to replenish steroidogenic cells of the zG and the inner cortex over time. Both the fate of progenitor cells and aldosterone production by steroidogenic cells in the zG are regulated by Wnt/β-catenin signaling, but the cell-specific effects of individual WNT ligands in the adrenal cortex are not fully understood. To further characterize Wnt signaling components crucial for progenitor cell fate and zG identity, we analyzed mouse adrenals using single molecule in situ hybridization, which revealed the previously unknown expression of Wnt2b exclusively in the adrenal capsule. Wnt2b is co-expressed in the capsule with the Wnt signaling potentiator Rspo3, the loss of which causes zG depletion and reduced adrenal size in mice. Therefore, we hypothesized that capsular WNT2B activates Wnt signaling in the underlying zG to maintain the undifferentiated state of progenitor cells. To define the role of WNT2B in these processes, we first generated whole body Wnt2b knockout (KO) mice, which exhibit complete zG loss, as defined by known markers of zG identity (β-catenin and DAB2). To more fully determine the mechanism by which Wnt2b deletion results in zG loss, we crossed Wnt2b-floxed and capsule-specific Gli1-CreERT2 mice to generate a Wnt2b conditional knockout (cKO) model and study the effects of Wnt2b loss on the zG during homeostasis of the adult adrenal cortex. Gli1-CreERT2 activation by tamoxifen in 6-week-old mice significantly decreased Wnt2b expression and resulted in a lower adrenal-to-body weight ratio in Wnt2b cKOs compared to controls four weeks later. Adrenocortical proliferation (Ki67) was also significantly decreased in Wnt2b cKO mice, suggesting that WNT2B may promote progenitor cell self-renewal. To characterize the consequences of WNT2B loss on canonical Wnt signaling, we assessed activation of β-catenin, the primary Wnt signaling effector. High β-catenin activity in the zG observed in wild-type mice was disrupted in Wnt2b cKO mice, together with markedly reduced expression of adrenocortical Wnt target genes Axin2 and Wnt4. In addition, Wnt2b loss resulted in downregulation of steroidogenic genes Cyp11b2 and Hsd3b6. Together, these data reveal that capsule-derived WNT2B is required for zG differentiation and maintenance, potentially through activating adrenocortical Wnt/β-catenin signaling and downstream target gene expression involved in both progenitor cell fate and steroid-producing cell function. Studies to more fully elucidate the dynamic effects of WNT2B on the adrenal zG are ongoing as they have important implications for adrenal homeostasis and disease, including both primary adrenal failure and neoplasia.

scholarly journals Latent Adrenal Insufficiency: From Concept to Diagnosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Nada Younes ◽  
Isabelle Bourdeau ◽  
Andre Lacroix
Keyword(s):  
Adrenal Insufficiency ◽  
Adrenal Cortex ◽  
Standard Dose ◽  
Signs And Symptoms ◽  
Serum Cortisol ◽  
Zona Glomerulosa ◽  
Adrenocortical Function ◽  
Adrenal Crisis ◽  
Zona Fasciculata ◽  
Adrenal Androgen

Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of autoimmune origin, resulting in glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies. Initial signs and symptoms can be nonspecific, contributing to late diagnosis. Loss of zona glomerulosa function may precede zona fasciculata and reticularis deficiencies. Patients present with hallmark manifestations including fatigue, weight loss, abdominal pain, melanoderma, hypotension, salt craving, hyponatremia, hyperkalemia, or acute adrenal crisis. Diagnosis is established by unequivocally low morning serum cortisol/aldosterone and elevated ACTH and renin concentrations. A standard dose (250 µg) Cosyntropin stimulation test may be needed to confirm adrenal insufficiency (AI) in partial deficiencies. Glucocorticoid and mineralocorticoid substitution is the hallmark of treatment, alongside patient education regarding dose adjustments in periods of stress and prevention of acute adrenal crisis. Recent studies identified partial residual adrenocortical function in patients with AI and rare cases have recuperated normal hormonal function. Modulating therapies using rituximab or ACTH injections are in early stages of investigation hoping it could maintain glucocorticoid residual function and delay complete destruction of adrenal cortex.

Long-term trophic action of α-melanocyte-stimulating hormone on the zona glomerulosa of the rat adrenal cortex

1986 ◽  
Vol 112 (3) ◽  
pp. 404-408 ◽  
Author(s):  
Claudia Robba ◽  
Piera Rebuffat ◽  
Giuseppina Mazzocchi ◽  
Gastone G. Nussdorfer
Keyword(s):  
Plasma Level ◽  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Short Term ◽  
Melanocyte Stimulating Hormone ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells ◽  
Stimulating Hormone

Abstract. The effects of α-melanocyte-stimulating hormone (α-MSH) on the rat adrenal cortex were investigated by coupled morphometric and radioimmunological techniques. Short-term α-MSH administration provoked a significant increase in the aldosterone plasma level along with a notable lipid droplet depletion in zona glomerulosa cells. Long-term α-MSH treatment induced a notable hypertrophy of zona glomerulosa cells and a further rise in the blood concentration of aldosterone. α-MSH did not affect zona fasciculata morphology and corticosterone plasma level. The possibility is discussed that α-MSH may be specifically involved in the control of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force

2016 ◽  
Vol 75 (6) ◽  
pp. 952-957 ◽  
Author(s):  
Cindy Strehl ◽  
Johannes W J Bijlsma ◽  
Maarten de Wit ◽  
Maarten Boers ◽  
Nele Caeyers ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rheumatic Diseases ◽  
Task Force ◽  
Convincing Evidence ◽  
Glucocorticoid Therapy ◽  
Patient Specific ◽  
Glucocorticoid Treatment ◽  
Low Level ◽  
Study Results

There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of >10 mg/day the risk of harm is elevated. At dosages between >5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk.

Control of steroidogenesis by the calcium messenger system in human adrenocortical cells

1991 ◽  
Vol 6 (1) ◽  
pp. 45-51 ◽  
Author(s):  
S. M. Laird ◽  
J. P. Hinson ◽  
G. P. Vinson ◽  
N. Mallick ◽  
S. Kapas ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Adrenal Cortex ◽  
Calcium Ionophore ◽  
Zona Glomerulosa ◽  
Adrenocortical Function ◽  
Ionophore A23187 ◽  
Adrenocortical Cells ◽  
Kinase C ◽  
Messenger System

ABSTRACT The involvement of the calcium messenger system in the control of steroidogenesis in the rat and bovine adrenal cortex has been studied extensively. However the role of these second messengers in the control of human adrenocortical function is not established. This was therefore studied by incubating collagenase-dispersed human adrenocortical cells with the calcium ionophore A23187 and the protein kinase C activator phorbol 12-myristate 13-acetate (TPA). The effects of the calcium channel blocker verapamil on basal and stimulated steroidogenesis were also studied. Both TPA (1 pmol/l–10 μmol/l) and A23187 (1 nmol/l–10 μmol/l) caused a dose-dependent increase in cortisol, aldosterone and corticosterone production. Verapamil (10 μmol/l) inhibited the increase in aldosterone, corticosterone and cortisol produced in response to ACTH(1–24), potassium, and desacetyl-αMSH. Unlike previous results in the rat, these effects were not specific for aldosterone secretion. The results suggest that, as in other species, calcium mobilization and protein kinase C activation have a role in the control of steroidogenesis in the human adrenal cortex. However, in contrast to the rat, these mechanisms appear to be involved in the control of steroidogenesis in both the zona glomerulosa and inner zone cells.

scholarly journals Dlk1 Up-Regulates Gli1 Expression in Male Rat Adrenal Capsule Cells Through the Activation of β1 Integrin and ERK1/2

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4675-4684 ◽  
Author(s):  
Leonardo Guasti ◽  
Dominic Cavlan ◽  
Kathryn Cogger ◽  
Zahida Banu ◽  
Amreen Shakur ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Sonic Hedgehog ◽  
Adipocyte Differentiation ◽  
Renin Angiotensin System ◽  
Zona Glomerulosa ◽  
Male Rat ◽  
Β1 Integrin ◽  
Angiotensin System ◽  
Epidermal Growth ◽  
Established Role

The development and maintenance of the zones of the adrenal cortex and their steroidal output are extremely important in the control of gluconeogenesis, the stress response, and blood volume. Sonic Hedgehog (Shh) is expressed in the adrenal cortex and signals to capsular cells, which can respond by migrating into the cortex and converting into a steroidogenic phenotype. Delta-like homologue 1 (Dlk1), a member of the Notch/Delta/Serrate family of epidermal growth factor-like repeat-containing proteins, has a well-established role in inhibiting adipocyte differentiation. We demonstrate that Shh and Dlk1 are coexpressed in the outer undifferentiated zone of the male rat adrenal and that Dlk1 signals to the adrenal capsule, activating glioma-associated oncogene homolog 1 transcription in a β1 integrin- and Erk1/2-dependent fashion. Moreover, Shh and Dlk1 expression inversely correlates with the size of the zona glomerulosa in rats after manipulation of the renin-angiotensin system, suggesting a role in the homeostatic maintenance of the gland.

ASSESSMENT OF A TEST OF ADRENOCORTICAL FUNCTION USING β1–25 CORTICOTROPHIN

1969 ◽  
Vol 44 (4) ◽  
pp. 513-516
Author(s):  
K. WHALEY ◽  
W. P. SOUTTER ◽  
W. C. DICK ◽  
G. NUKI ◽  
W. W. DOWNIE
Keyword(s):  
Adrenal Cortex ◽  
Corticosteroid Therapy ◽  
Adrenocortical Function ◽  
Normal Range ◽  
Simple Method ◽  
Maximal Stimulation ◽  
Synthetic Polypeptides ◽  
Range Of Values ◽  
Stimulation Of

SUMMARY In ten patients with a variety of rheumatic disorders the changes in plasma corticosteroid (11-OHCS) levels have been studied after adrenocortical stimulation by a continuous 5 hr. infusion of Synacthen (Ciba) or by a single i.v. injection of 200 i.u. (320 μg.) Pentacosactride (Sandoz). Comparable increases were obtained using both synthetic polypeptides. It is suggested that administration of Pentacosactride intravenously is a simple method of obtaining prolonged maximal stimulation of the adrenal cortex. A normal range of values of plasma 11-OHCS, obtained from 28 subjects, is given, and it is shown that the results are reproducible. The results of tests in six subjects with secondary adrenal atrophy due to long-term corticosteroid therapy indicate that the test can discriminate between normal and subnormal adrenocortical function.

Adrenal disease

2018 ◽  
Author(s):  
John Newell-Price ◽  
Alia Munir ◽  
Miguel Debono
Keyword(s):  
Adrenal Insufficiency ◽  
Adrenal Cortex ◽  
Chromaffin Cells ◽  
Zona Glomerulosa ◽  
Adrenocortical Function ◽  
Primary Adrenal Insufficiency ◽  
Rare Tumours ◽  
Consequent Reduction ◽  
Hypothalamic Function ◽  
Adrenal Disease

This chapter reviews the clinical features, diagnosis, and treatment of three adrenal diseases: adrenal insufficiency, primary aldosteronism (hyperaldosteronism), and phaeochromocytoma. Adrenal insufficiency is a disorder characterized by impaired adrenocortical function. In primary adrenal insufficiency, destruction of the adrenal cortex results in a decreased production of glucocorticoids, mineralocorticoids, and/or androgens. Secondary adrenal insufficiency is due to disordered pituitary and hypothalamic function resulting in decreased secretion of adrenocorticotropic hormone or corticotrophin-releasing hormone, with consequent reduction in glucocorticoid and/or androgen secretion. Aldosterone is produced in the zona glomerulosa of the adrenal cortex. Abnormal overproduction of aldosterone results in autonomous primary hyperaldosteronism, leading to hypertension and hypokalaemia. Phaeochromocytomas are rare tumours of the adrenal medulla, arising from chromaffin cells, and produce catecholamines. Tumours arising from extra-adrenal ganglia, both sympathetic and parasympathetic, are called paragangliomas. As the majority of sympathetic paragangliomas secrete catecholamines, they are also called extra-adrenal phaeochromocytomas.

Sign in / Sign up

Export Citation Format

Share Document