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Questions and Answers
What hormone is released from the hypothalamus to initiate glucocorticoid secretion?
What hormone is released from the hypothalamus to initiate glucocorticoid secretion?
Which enzyme is activated by the dissociated α-subunit of the G-protein in the zona fasciculata cells?
Which enzyme is activated by the dissociated α-subunit of the G-protein in the zona fasciculata cells?
Which pathway provides most of the cholesterol used for steroid hormone synthesis?
Which pathway provides most of the cholesterol used for steroid hormone synthesis?
What is the primary function of protein kinase A (PKA) in the synthesis of adrenal steroids?
What is the primary function of protein kinase A (PKA) in the synthesis of adrenal steroids?
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Which subunit of the G-protein is primarily involved in the activation of cellular responses in zona fasciculata cells?
Which subunit of the G-protein is primarily involved in the activation of cellular responses in zona fasciculata cells?
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What is the role of cholesteryl ester hydrolase (CEH) in cholesterol mobilization?
What is the role of cholesteryl ester hydrolase (CEH) in cholesterol mobilization?
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What is the primary source of the inferior suprarenal arteries?
What is the primary source of the inferior suprarenal arteries?
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Where does the central vein of the right adrenal gland drain?
Where does the central vein of the right adrenal gland drain?
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During the process of glucocorticoid secretion, what molecule does cAMP activate?
During the process of glucocorticoid secretion, what molecule does cAMP activate?
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What regulates the synthesis of cortisol in zona fasciculata cells?
What regulates the synthesis of cortisol in zona fasciculata cells?
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The adrenal medulla derives from which embryonic cells?
The adrenal medulla derives from which embryonic cells?
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What hormones are primarily produced by the chromaffin cells of the adrenal medulla?
What hormones are primarily produced by the chromaffin cells of the adrenal medulla?
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Why is the adrenal medulla described as an 'overgrown sympathetic ganglion'?
Why is the adrenal medulla described as an 'overgrown sympathetic ganglion'?
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What role do sympathetic nerves play in the function of the adrenal medulla during stress?
What role do sympathetic nerves play in the function of the adrenal medulla during stress?
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How does the adrenal medulla relate to the sympathetic nervous system?
How does the adrenal medulla relate to the sympathetic nervous system?
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What is the effect of catecholamines released by the adrenal medulla on the body?
What is the effect of catecholamines released by the adrenal medulla on the body?
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What can result from excess glucocorticoids in relation to bone health?
What can result from excess glucocorticoids in relation to bone health?
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How do glucocorticoids affect the immune system in short-term elevations?
How do glucocorticoids affect the immune system in short-term elevations?
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What initial effect do supraphysiologic levels of glucocorticoids have on the central nervous system?
What initial effect do supraphysiologic levels of glucocorticoids have on the central nervous system?
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What are the chronic effects of decreased glucose uptake in muscle and adipose tissue?
What are the chronic effects of decreased glucose uptake in muscle and adipose tissue?
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What is a consequence of excess glucocorticoids on healing tissue?
What is a consequence of excess glucocorticoids on healing tissue?
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What effect do glucocorticoids have on cardiac output at high doses?
What effect do glucocorticoids have on cardiac output at high doses?
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Which statement is true regarding glucocorticoids and the fetus?
Which statement is true regarding glucocorticoids and the fetus?
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What might long-term elevations of cortisol lead to in terms of macrophage function?
What might long-term elevations of cortisol lead to in terms of macrophage function?
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Which receptor type does norepinephrine have the least effect on?
Which receptor type does norepinephrine have the least effect on?
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What is the role of corticotropin-releasing hormone (CRH) in catecholamine synthesis?
What is the role of corticotropin-releasing hormone (CRH) in catecholamine synthesis?
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Which enzyme is responsible for converting norepinephrine into epinephrine?
Which enzyme is responsible for converting norepinephrine into epinephrine?
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What initiates the acute regulation of catecholamine release in response to stress?
What initiates the acute regulation of catecholamine release in response to stress?
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How does sustained ACTH and cortisol levels impact catecholamine synthesis over time?
How does sustained ACTH and cortisol levels impact catecholamine synthesis over time?
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Which process describes the immediate release of catecholamines in response to stress?
Which process describes the immediate release of catecholamines in response to stress?
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Which amino acid is the starting point for catecholamine biosynthesis?
Which amino acid is the starting point for catecholamine biosynthesis?
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What occurs as a result of sympathetic stimulation during catecholamine synthesis?
What occurs as a result of sympathetic stimulation during catecholamine synthesis?
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What is the primary function of Steroidogenic acute regulatory protein (StAR)?
What is the primary function of Steroidogenic acute regulatory protein (StAR)?
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Which enzyme is considered the rate-limiting step in the synthesis pathway of glucocorticoids?
Which enzyme is considered the rate-limiting step in the synthesis pathway of glucocorticoids?
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What effect does ACTH have on the activity of cholesterol esterase (CEH)?
What effect does ACTH have on the activity of cholesterol esterase (CEH)?
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Where does the conversion of cholesterol into pregnenolone take place?
Where does the conversion of cholesterol into pregnenolone take place?
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Which of the following statements about cortisol is correct?
Which of the following statements about cortisol is correct?
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What role does ACTH play in the adrenal gland?
What role does ACTH play in the adrenal gland?
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Which of the following hormones is primarily synthesized from pregnenolone?
Which of the following hormones is primarily synthesized from pregnenolone?
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What happens to ACTH and glucocorticoid levels in the morning before awakening?
What happens to ACTH and glucocorticoid levels in the morning before awakening?
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What is the primary factor that stimulates the secretion of aldosterone?
What is the primary factor that stimulates the secretion of aldosterone?
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Which cell type expresses aldosterone synthase necessary for aldosterone production?
Which cell type expresses aldosterone synthase necessary for aldosterone production?
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What initiates the conversion of Angiotensin to Angiotensin I in the RAAS pathway?
What initiates the conversion of Angiotensin to Angiotensin I in the RAAS pathway?
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Which action is NOT a function of Angiotensin II?
Which action is NOT a function of Angiotensin II?
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Which of the following is mostly responsible for the regulation of mineralocorticoids?
Which of the following is mostly responsible for the regulation of mineralocorticoids?
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What is the primary function of cortisol in the body?
What is the primary function of cortisol in the body?
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What effect does protein kinase A (PKA) have on target proteins within the cell?
What effect does protein kinase A (PKA) have on target proteins within the cell?
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Which component of the G-protein is primarily responsible for activating adenylyl cyclase in zona fasciculata cells?
Which component of the G-protein is primarily responsible for activating adenylyl cyclase in zona fasciculata cells?
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What is the role of ACTH in cortisol synthesis?
What is the role of ACTH in cortisol synthesis?
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What process involves cholesterol being released from intracellular stores in the context of adrenal steroid synthesis?
What process involves cholesterol being released from intracellular stores in the context of adrenal steroid synthesis?
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Where does the conversion of cholesterol into testosterone or estrogen primarily occur?
Where does the conversion of cholesterol into testosterone or estrogen primarily occur?
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How does increased cAMP influence adrenal steroid hormone synthesis?
How does increased cAMP influence adrenal steroid hormone synthesis?
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What is the source of most cholesterol used for steroid hormone synthesis?
What is the source of most cholesterol used for steroid hormone synthesis?
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What is the primary function of aldosterone produced by the zona glomerulosa?
What is the primary function of aldosterone produced by the zona glomerulosa?
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Which zone of the adrenal cortex is primarily responsible for glucocorticoid secretion?
Which zone of the adrenal cortex is primarily responsible for glucocorticoid secretion?
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Which component forms the adrenal medulla during embryonic development?
Which component forms the adrenal medulla during embryonic development?
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How does the adrenal cortex primarily respond to long-term stress?
How does the adrenal cortex primarily respond to long-term stress?
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What type of hormones does the zona reticularis secrete?
What type of hormones does the zona reticularis secrete?
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What is the relationship between the hypothalamus and the anterior pituitary in hormone regulation?
What is the relationship between the hypothalamus and the anterior pituitary in hormone regulation?
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What is the primary physiological function of catecholamines released during stress?
What is the primary physiological function of catecholamines released during stress?
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What initiates the release of catecholamines from the adrenal medulla during stress?
What initiates the release of catecholamines from the adrenal medulla during stress?
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What is the primary role of the side-chain cleavage enzyme (SCC) in steroid hormone synthesis?
What is the primary role of the side-chain cleavage enzyme (SCC) in steroid hormone synthesis?
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Which factor primarily upregulates the expression of LDL receptors during glucocorticoid synthesis?
Which factor primarily upregulates the expression of LDL receptors during glucocorticoid synthesis?
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What occurs as a result of increased activity of Steroidogenic acute regulatory protein (StAR)?
What occurs as a result of increased activity of Steroidogenic acute regulatory protein (StAR)?
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During glucocorticoid synthesis, where does the conversion of pregnenolone to cortisol take place?
During glucocorticoid synthesis, where does the conversion of pregnenolone to cortisol take place?
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How does ACTH influence steroid hormone synthesis?
How does ACTH influence steroid hormone synthesis?
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What is the primary end product of the adrenal steroidogenesis pathway initiated by cholesterol?
What is the primary end product of the adrenal steroidogenesis pathway initiated by cholesterol?
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What is a direct effect of fluctuations in ACTH levels throughout the day?
What is a direct effect of fluctuations in ACTH levels throughout the day?
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Which enzyme converts cholesterol directly into pregnenolone?
Which enzyme converts cholesterol directly into pregnenolone?
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Which receptor type does norepinephrine stimulate the least?
Which receptor type does norepinephrine stimulate the least?
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What is the primary role of cortisol in catecholamine synthesis?
What is the primary role of cortisol in catecholamine synthesis?
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What initiates the acute regulation of catecholamine release?
What initiates the acute regulation of catecholamine release?
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How does chronic stress influence catecholamine production?
How does chronic stress influence catecholamine production?
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What is the function of tyrosine hydroxylase (TH) in catecholamine biosynthesis?
What is the function of tyrosine hydroxylase (TH) in catecholamine biosynthesis?
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What is the role of sympathetic stimulation in catecholamine release?
What is the role of sympathetic stimulation in catecholamine release?
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What process is involved in the conversion of norepinephrine into epinephrine?
What process is involved in the conversion of norepinephrine into epinephrine?
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What stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH)?
What stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH)?
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Study Notes
Inferior Suprarenal Arteries
- Arise from the renal arteries, which also supply the kidneys.
- Blood flows into the adrenal glands through small vessels, exiting via a central vein.
- Right adrenal gland's vein drains into inferior vena cava; left adapts to renal vein.
Adrenal Glands - Embryology
- Adrenal medulla originates from neural crest cells during embryonic development.
- Chromaffin cells in the medulla produce catecholamines: adrenaline and noradrenaline.
- Medulla acts as an "overgrown sympathetic ganglion,” closely linked to the sympathetic nervous system (SNS).
Medulla Function and Hormonal Release
- Activated by stress signals from the SNS, the adrenal medulla releases hormones directly into the bloodstream.
- Zona fasciculata produces cortisol, regulating metabolism and stress responses.
- Gonads convert cholesterol into testosterone or estrogen, regulating reproductive functions.
Regulation of Glucocorticoid Secretion
- Corticotrophin-releasing hormone (CRH) is released by the hypothalamus.
- CRH stimulates adrenocorticotropic hormone (ACTH) release from the anterior pituitary.
- ACTH increases cortisol synthesis in the zona fasciculata.
Mechanism of ACTH Action
- ACTH binds to G-protein coupled receptors, activating a G-protein with α-subunit (Gs).
- Activation leads to increased cAMP and subsequent activation of enzymes for cortisol production.
- Protein kinase A (PKA) further phosphorylates target proteins, regulating steroid synthesis.
Cholesterol Mobilization for Steroidogenesis
- Most cholesterol for hormones is obtained from LDL, involving the upregulation of LDL receptors.
- Cholesterol is stored in lipid droplets and released by cholesteryl ester hydrolase (CEH).
- PKA enhances the transport of cholesterol into mitochondria via steroidogenic acute regulatory protein (StAR).
Steroid Hormone Synthesis Pathway
- Begins with the cleavage of cholesterol side chains at the inner mitochondrial membrane, forming pregnenolone.
- A series of enzymes, including side-chain cleavage enzyme (SCC), convert pregnenolone into cortisol.
- SCC is the rate-limiting step in glucocorticoid synthesis.
Effects of Glucocorticoids on Various Tissues
- Crucial for fetal development of lungs and liver.
- Physiological glucocorticoid levels do not harm bone; excess impairs bone formation through various mechanisms.
- Beneficial for tissue healing, but high levels can inhibit fibroblast activity, affecting recovery.
Cardiovascular and CNS Effects
- Increase sympathy activity in peripheral vessels and heart, leading to hypertension.
- Enhances cardiac output and salt/water retention independently of mineralocorticoids.
- Physiological levels influence mood; excess glucocorticoids cause emotional disturbances.
Immune System Impact
- Short-term glucocorticoid elevations enhance neutrophil activity and lymphocyte response.
- Chronic high glucocorticoid levels impair macrophage function and lymphocyte production, hindering healing.
Catecholamine Synthesis Regulation
- Sympathetic stimulation, ACTH, and cortisol increase catecholamine synthesis.
- Stress activates the hypothalamus, releasing CRH to stimulate ACTH and cortisol production.
Stress Response and Acute Regulation
- Acute sympathetic stimulation releases acetylcholine, promoting catecholamine exocytosis in response to stress.
- Chronic regulation involves sustained ACTH increasing catecholamine levels over time.
Catecholamine Biosynthesis Pathway
- Begins with tyrosine that is converted to L-DOPA, then to dopamine, and finally into norepinephrine via key enzymes.
- This pathway occurs inside chromaffin cells in response to neuronal signals and stress.
Adrenal Glands Overview
- Adrenal glands respond to stress by increasing heart rate, blood pressure, and energy through chemical signals.
- The adrenal gland consists of two main parts: the adrenal cortex and the adrenal medulla, which have different developmental origins and functions.
Adrenal Cortex
- Derived from mesoderm, forming the outer layer of the adrenal gland.
- Produces essential steroid hormones with three distinct zones:
- Zona Glomerulosa: Smallest zone, secretes aldosterone for blood pressure regulation via sodium and water balance.
- Zona Fasciculata: Largest zone, produces cortisol for metabolism regulation, immune response, and stress response.
- Zona Reticularis: Secretes androgens, precursors for sex steroids like testosterone and estrogen.
Adrenal Medulla
- Developed from neural crest cells, functions as an “overgrown sympathetic ganglion”.
- Responsible for catecholamine secretion, particularly epinephrine during stress.
Hypothalamic-Pituitary Axis (HPA)
- The hypothalamus releases hormones (e.g., CRH, TRH, GnRH), which regulate the anterior pituitary hormones.
- Anterior pituitary hormones influence various endocrine glands’ activities.
Regulation of Glucocorticoids
- Corticotrophin-releasing hormone (CRH) stimulates adrenocorticotropic hormone (ACTH) release from the anterior pituitary.
- ACTH promotes cortisol synthesis in the adrenal cortex, specifically in zona fasciculata.
- Involves activation of G-protein coupled receptors, increasing cAMP levels, which activates protein kinase A (PKA) leading to cortisol production.
Synthesis of Adrenal Steroids
- Cholesterol is a precursor for all steroid hormone synthesis, primarily sourced from LDL through an exogenous pathway.
- Cholesterol mobilization into mitochondria is facilitated by PKA and steroidogenic acute regulatory protein (StAR).
- Initial step in steroid hormone synthesis involves converting cholesterol into pregnenolone, followed by a cascade of enzyme-driven reactions producing final hormones, such as cortisol.
Mineralocorticoid Regulation
- Aldosterone production depends on aldosterone synthase, expressed exclusively in zona glomerulosa cells.
- Major regulators include:
- Angiotensin II from the renin-angiotensin-aldosterone system (RAAS)
- Serum potassium levels (K+)
Renin-Angiotensin-Aldosterone System (RAAS)
- Renin release from the kidney in response to reduced perfusion converts angiotensin to angiotensin I.
- Angiotensin II functions include vasoconstriction, stimulating aldosterone secretion, and promoting sodium reabsorption in kidneys.
Catecholamine Synthesis
- Stress activates hypothalamus, releasing CRH, which triggers ACTH production.
- ACTH enhances catecholamine synthesis and secretion (norepinephrine and epinephrine) in the adrenal medulla.
- Two pathways regulate catecholamine release:
- Chronic Regulation: Involvement of cortisol and ACTH for long-term stress responses, leading to increased production of epinephrine.
- Acute Regulation: Neuronal stimulation through acetylcholine rapidly induces catecholamine exocytosis from chromaffin cells.
Catecholamine Biosynthesis Pathway
- Begins with tyrosine, which is converted to catecholamines through enzymatic reactions involving:
- Tyrosine Hydroxylase (TH): Converts tyrosine to L-DOPA.
- DOPA Decarboxylase (DD): Converts L-DOPA to dopamine.
- Dopamine β-hydroxylase (DH): Transforms dopamine into norepinephrine.
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Test your knowledge on the anatomy of the adrenal glands with this quiz. Explore the origins of the inferior suprarenal arteries and their role in supplying blood to the adrenal glands. Understand the venous drainage of the adrenal glands on both sides for a comprehensive overview.
