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

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.

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ACUTE ENZYME HISTOCHEMICAL CHANGES IN THE ZONA GLOMERULOSA OF THE RAT ADRENAL CORTEX

Acta Endocrinologica ◽

10.1530/acta.0.0670117 ◽

1971 ◽

Vol 67 (1) ◽

pp. 117-126

Author(s):

J. D. Elema ◽

M. J. Hardonk ◽

A. Arends

Keyword(s):

Peritoneal Dialysis ◽

Adrenal Cortex ◽

Renin Angiotensin System ◽

Zona Glomerulosa ◽

Experimental Conditions ◽

Angiotensin System ◽

Renin Angiotensin ◽

Histochemical Changes ◽

Increased Activity ◽

Total Nephrectomy

ABSTRACT In order to determine whether the increased enzyme histochemical activity of the zona glomerulosa of the rat adrenal cortex, as seen after peritoneal dialysis with 5 % glucose, is mediated by the renin-angiotensin system, and whether the increased activity as seen after total nephrectomy is a direct effect of changes in potassium balance, the effect of suppression of the renin-angiotensin system and of depletion of body potassium on these findings was investigated. Suppression of renin-angiotensin system activity and depletion of body potassium was accomplished by treatment of the rats with 2.5 mg deoxycorticosterone acetate given subcutaneously daily for 4 weeks. This treatment resulted in a delayed activation of the zona glomerulosa after peritoneal dialysis and a complete lack of reaction after total nephrectomy; the findings support the above mentioned assumptions about the manner in which the zona glomerulosa is activated in these experimental conditions.

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ACUTE ENZYME HISTOCHEMICAL CHANGES IN THE ZONA GLOMERULOSA OF THE RAT ADRENAL CORTEX

Acta Endocrinologica ◽

10.1530/acta.0.0590519 ◽

1968 ◽

Vol 59 (3) ◽

pp. 519-528 ◽

Cited By ~ 2

Author(s):

J. D. Elema ◽

M. J. Hardonk ◽

Joh. Koudstaal ◽

A. Arends

Keyword(s):

Adrenal Cortex ◽

Direct Effect ◽

Renin Angiotensin System ◽

Zona Glomerulosa ◽

Bilateral Nephrectomy ◽

Angiotensin System ◽

Renin Angiotensin ◽

Histochemical Changes ◽

Total Nephrectomy

ABSTRACT In order to evaluate a possible role of the renin-angiotensin system in enzyme histochemical changes of the rat adrenal cortex seen after acute hyponatraemia, the effect of a preceding total nephrectomy was investigated. By this procedure it was found that the alterations were largely inhibited. The results therefore favour a role of the renin-angiotensin system in these changes. Moreover it was found that bilateral nephrectomy alone also induced an enhanced zona glomerulosa activity which may be due to a direct effect of changes in potassium homoeostasis.

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Presence of renin within intramitochondrial dense bodies of the rat adrenal cortex

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.271.3.e439 ◽

1996 ◽

Vol 271 (3) ◽

pp. E439-E450 ◽

Cited By ~ 13

Author(s):

J. Peters ◽

B. Kranzlin ◽

S. Schaeffer ◽

J. Zimmer ◽

S. Resch ◽

...

Keyword(s):

Adrenal Cortex ◽

Renin Angiotensin System ◽

Zona Glomerulosa ◽

Specific Expression ◽

Angiotensin System ◽

Adrenal Cells ◽

Dense Bodies ◽

Glomerulosa Cells ◽

New Evidence ◽

Renin Content

It has been suggested that tissue-specific expression of the genes of the renin-angiotensin system (RAS) leads to local generation of angiotensin (ANG) II with specific physiological implications. We demonstrate here that an intracellular RAS exists in adrenal glomerulosa cells; 60 h after bilateral nephrectomy and hemodialysis, renin and prorenin were eliminated from the circulation, whereas intra-adrenal renin content increased (control rats: 2 +/- 0.5 ng ANG I.mg-1.h-1; anephric rats: 25 +/- 2). Thus renin is produced locally within adrenal cells. We obtained immunocytochemical and biochemical evidence for the presence of renin within intramitochondrial dense bodies of the zona glomerulosa. After nephrectomy, dense bodies increased in number, size, and renin content (control rats: 2.5 +/- 0.7 ngANGI.mg-1.h-1; anephric rats: 43 +/- 7). Angiotensin-converting enzyme (ACE) was also present within mitochondria and their dense bodies. In addition, in adrenal cortex of anephric rats, giant dense bodies were observed, which contain renin and strongly react with an anti-angiotensinogen antibody. The localization of renin, ACE, and angiotensinogen at these sites provides new evidence for the existence of an intracellular adrenal RAS.

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Effects of renovascular hypertension on rat adrenal zona glomerulosa

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100083783 ◽

1978 ◽

Vol 36 (2) ◽

pp. 582-583

Author(s):

G. Mazzocchi ◽

P. Rebuffat ◽

C. Robba ◽

P. Vassanelli ◽

G. G. Nussdorfer

Keyword(s):

Renovascular Hypertension ◽

Left Kidney ◽

Renin Angiotensin System ◽

Plasma Renin ◽

Zona Glomerulosa ◽

Ultrastructural Changes ◽

Albino Rats ◽

Left Renal Artery ◽

Angiotensin System ◽

And Control

It is well known that the rat adrenal zona glomerulosa steroidogenic activity is controlled by the renin-angiotensin system. The ultrastructural changes in the rat zona glomerulosa cells induced by renovascular hypertension were described previously, but as far as we are aware no correlated biochemical and morphometric investigations were performed.Twenty adult male albino rats were divided into 2 experimental groups. One group was subjected to restriction of blood flow to the left kidney by the application of a silver clip about the left renal artery. The other group was sham-operated and served as a control. Renovascular hypertension developed in about 10 days: sistolic blood pressure averaged 165 ± 6. 4 mmHg, whereas it was about 110 ± 3. 8 mmHg in the control animals. The hypertensive and control rats were sacrificed 20 days after the operation. The blood was collected and plasma renin activity was determined by radioimmunological methods. The aldosterone concentration was radioimmunologically assayed both in the plasma and in the homogenate of the left capsular adrenal gland.

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The Relationship between the Adrenal Tissue Renin-Angiotensin System, Internalization of the Type I Angiotensin II Receptor (AT1) and Angiotensin II Function in the Rat Adrenal Zona Glomerulosa Cell

Advances in Experimental Medicine and Biology - Tissue Renin-Angiotensin Systems ◽

10.1007/978-1-4899-0952-7_22 ◽

1995 ◽

pp. 319-329 ◽

Cited By ~ 6

Author(s):

G. P. Vinson ◽

M. M. Ho ◽

J. R. Puddefoot ◽

R. Teja ◽

S. Barker ◽

...

Keyword(s):

Angiotensin Ii ◽

Renin Angiotensin System ◽

Zona Glomerulosa ◽

Type I ◽

Angiotensin Ii Receptor ◽

Angiotensin System ◽

Renin Angiotensin ◽

Adrenal Tissue ◽

The Relationship

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Evidence that 19-hydroxyandrostenedione is secreted by the adrenal cortex and is under the control of ACTH and the renin-angiotensin system in man

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(82)91478-4 ◽

1982 ◽

Vol 105 (2) ◽

pp. 610-614 ◽

Cited By ~ 12

Author(s):

Hisahiko Sekihara

Keyword(s):

Adrenal Cortex ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin

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Adrenal gland disorders

10.1093/med/9780199232222.003.0068 ◽

2011 ◽

Author(s):

Gary Butler ◽

Jeremy Kirk

Keyword(s):

Adrenal Gland ◽

Adrenal Insufficiency ◽

Steroid Hormones ◽

Adrenal Cortex ◽

Renin Angiotensin System ◽

Cortisol Secretion ◽

Aldosterone Secretion ◽

Angiotensin System ◽

Adrenal Steroid ◽

Endocrine Axis

Physiology 236Adrenal insufficiency 238Adrenal steroid excess 246Further reading 247The adrenal cortex, which produces steroid hormones, is under the control of both the hypothalamo–pituitary–adrenal (HPA) endocrine axis, which regulates cortisol secretion, and the renin–angiotensin system, which regulates aldosterone secretion (Figs 8.1 and ...

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Role of adrenal renin-angiotensin system in the control of aldosterone secretion in sodium-restricted rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.278.6.e1027 ◽

2000 ◽

Vol 278 (6) ◽

pp. E1027-E1030 ◽

Cited By ~ 24

Author(s):

Giuseppina Mazzocchi ◽

Ludwik K. Malendowicz ◽

Anna Markowska ◽

Giovanna Albertin ◽

Gastone G. Nussdorfer

Keyword(s):

Enzyme Inhibitor ◽

Renin Angiotensin System ◽

Zona Glomerulosa ◽

Normal Diet ◽

Angiotensin Ii Receptor ◽

Aldosterone Secretion ◽

Angiotensin System ◽

Renin Angiotensin

This study examined the effect of the pharmacological manipulation of adrenal renin-angiotensin system (RAS) on aldosterone secretion from in situ perfused adrenals of rats kept on a normal diet and sodium restricted for 14 days. Neither the angiotensin-converting enzyme inhibitor captopril nor the nonselective angiotensin II receptor antagonist saralasin and the AT1 receptor-selective antagonist losartan affected basal aldosterone output in normally fed rats. In contrast, they concentration dependently decreased aldosterone secretion in sodium-restricted animals, with maximal effective concentration ranging from 10− 7 to 10− 6 M. Captopril (10− 6 M), saralasin (10− 6 M), and losartan (10− 7 M) counteracted aldosterone response to 10 mM K+ in sodium-restricted rats but not in normally fed animals. Collectively, these findings provide evidence that adrenal RAS plays a role in the regulation of aldosterone secretion, but only under conditions of prolonged stimulation of zona glomerulosa probably leading to overexpression of adrenal RAS.

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