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Questions and Answers
Which hormone is involved in the stress response and stimulates the adrenal cortex?
Which hormone is involved in the stress response and stimulates the adrenal cortex?
- Progesterone
- Glucocorticoids
- Corticotropin-releasing hormone (correct)
- 18-Hydroxydehydrogenase
What reaction does the enzyme 21α-hydroxylase catalyze?
What reaction does the enzyme 21α-hydroxylase catalyze?
- Hydroxylation of progesterone (correct)
- Formation of aldosterone
- Oxidation of cholesterol
- Reduction of glucocorticoids
What does oxidation refer to in biochemical terms?
What does oxidation refer to in biochemical terms?
- Addition of hydrogen atoms
- Loss of oxygen atoms
- Loss of electrons (correct)
- Loss of hydrogen atoms
Which of the following is a product of hydroxylation on the 21st carbon of progesterone?
Which of the following is a product of hydroxylation on the 21st carbon of progesterone?
What is produced as an intermediate in the synthesis of aldosterone?
What is produced as an intermediate in the synthesis of aldosterone?
What is the primary role of glucocorticoids in metabolism?
What is the primary role of glucocorticoids in metabolism?
Where are hormone response elements (HREs) typically located in relation to the transcription initiation site?
Where are hormone response elements (HREs) typically located in relation to the transcription initiation site?
Which of the following is NOT a primary function of steroid hormones?
Which of the following is NOT a primary function of steroid hormones?
Cortisol is primarily involved in managing which process in the body?
Cortisol is primarily involved in managing which process in the body?
What triggers the secretion of mineralocorticoids?
What triggers the secretion of mineralocorticoids?
Which enzyme converts 11-deoxycortisol to cortisol?
Which enzyme converts 11-deoxycortisol to cortisol?
What is the role of aldosterone in the steroid hormone pathway?
What is the role of aldosterone in the steroid hormone pathway?
In the action of steroid hormones, which location serves as the site for hormone-receptor complex binding?
In the action of steroid hormones, which location serves as the site for hormone-receptor complex binding?
Which enzyme is responsible for catalyzing the conversion of corticosterone to aldosterone?
Which enzyme is responsible for catalyzing the conversion of corticosterone to aldosterone?
What type of receptor do estrogen hormones bind to in the target cells?
What type of receptor do estrogen hormones bind to in the target cells?
What is a common result of 21α-hydroxylase deficiency?
What is a common result of 21α-hydroxylase deficiency?
What is a key characteristic of CAH due to 3β-OH dehydrogenase deficiency?
What is a key characteristic of CAH due to 3β-OH dehydrogenase deficiency?
What symptom might indicate a deficiency in 17α-hydroxylase?
What symptom might indicate a deficiency in 17α-hydroxylase?
How does adrenal insufficiency affect the HPA axis?
How does adrenal insufficiency affect the HPA axis?
What is NOT typically produced in significant amounts in 3β-OH dehydrogenase deficiency?
What is NOT typically produced in significant amounts in 3β-OH dehydrogenase deficiency?
What enzyme deficiency leads to increased aldosterone levels and low sex hormones?
What enzyme deficiency leads to increased aldosterone levels and low sex hormones?
What is the inheritance pattern of Congenital Adrenal Hyperplasia (CAH)?
What is the inheritance pattern of Congenital Adrenal Hyperplasia (CAH)?
What is formed as a consequence of the lack of cortisol due to adrenal insufficiency in CAH?
What is formed as a consequence of the lack of cortisol due to adrenal insufficiency in CAH?
What is the primary deficiency in the salt-wasting form of congenital adrenal hyperplasia (CAH)?
What is the primary deficiency in the salt-wasting form of congenital adrenal hyperplasia (CAH)?
Which of the following clinical effects is directly caused by aldosterone deficiency in CAH?
Which of the following clinical effects is directly caused by aldosterone deficiency in CAH?
What is a consequence of the overproduction of deoxycorticosterone in CAH?
What is a consequence of the overproduction of deoxycorticosterone in CAH?
What results from the deficiency of 11-β-hydroxylase (CYP11B1) in CAH?
What results from the deficiency of 11-β-hydroxylase (CYP11B1) in CAH?
What gender-specific effect can result from excess androgen production in females with CAH?
What gender-specific effect can result from excess androgen production in females with CAH?
What is an important step in the management of CAH?
What is an important step in the management of CAH?
Which hormone's deficiency contributes to poor response to stress in CAH?
Which hormone's deficiency contributes to poor response to stress in CAH?
What is a major electrolyte imbalance associated with aldosterone deficiency in CAH?
What is a major electrolyte imbalance associated with aldosterone deficiency in CAH?
What is the first step in steroid hormone synthesis?
What is the first step in steroid hormone synthesis?
Which enzyme is responsible for converting pregnenolone to progesterone?
Which enzyme is responsible for converting pregnenolone to progesterone?
What role does the steroidogenic acute regulatory protein (StAR) play in steroid synthesis?
What role does the steroidogenic acute regulatory protein (StAR) play in steroid synthesis?
Which hormone is formed from the conversion of progesterone through a series of hydroxylation reactions?
Which hormone is formed from the conversion of progesterone through a series of hydroxylation reactions?
What is the rate-limiting step in the synthesis of steroid hormones?
What is the rate-limiting step in the synthesis of steroid hormones?
Which of the following enzymes is not involved in the synthesis of cortisol from progesterone?
Which of the following enzymes is not involved in the synthesis of cortisol from progesterone?
What type of molecule is a steroid hormone?
What type of molecule is a steroid hormone?
Which of the following statements about steroid hormone synthesis is true?
Which of the following statements about steroid hormone synthesis is true?
What modification is made to progesterone to form cortisol?
What modification is made to progesterone to form cortisol?
Where does the modification process for steroid synthesis predominantly occur?
Where does the modification process for steroid synthesis predominantly occur?
What is the process that replaces a hydrogen atom with a hydroxyl group in a substrate molecule called?
What is the process that replaces a hydrogen atom with a hydroxyl group in a substrate molecule called?
Which reaction involves the removal of hydrogen atoms and is a common oxidation process in biochemistry?
Which reaction involves the removal of hydrogen atoms and is a common oxidation process in biochemistry?
Which molecule is a precursor to both glucocorticoids and mineralocorticoids in steroid hormone synthesis?
Which molecule is a precursor to both glucocorticoids and mineralocorticoids in steroid hormone synthesis?
What type of enzymes are primarily responsible for catalyzing hydroxylation reactions in biological systems?
What type of enzymes are primarily responsible for catalyzing hydroxylation reactions in biological systems?
What is the product formed through the oxidation of the 18-hydroxyl group in 18-Hydroxycorticosterone?
What is the product formed through the oxidation of the 18-hydroxyl group in 18-Hydroxycorticosterone?
Which enzyme directly catalyzes the conversion of 11-deoxycortisol to cortisol?
Which enzyme directly catalyzes the conversion of 11-deoxycortisol to cortisol?
What is the role of the hormone-receptor complex in the mechanism of steroid hormone action?
What is the role of the hormone-receptor complex in the mechanism of steroid hormone action?
In the synthesis of aldosterone, which precursor is converted by the enzyme 18-hydroxylase?
In the synthesis of aldosterone, which precursor is converted by the enzyme 18-hydroxylase?
Which location within the cell signifies where steroid hormones typically exert their function?
Which location within the cell signifies where steroid hormones typically exert their function?
What type of steroid hormone does aldosterone primarily regulate electrolyte levels for?
What type of steroid hormone does aldosterone primarily regulate electrolyte levels for?
What clinical feature is most directly related to an excess of deoxycorticosterone in patients with CAH?
What clinical feature is most directly related to an excess of deoxycorticosterone in patients with CAH?
Which electrolyte imbalance is characteristic of aldosterone deficiency in congenital adrenal hyperplasia?
Which electrolyte imbalance is characteristic of aldosterone deficiency in congenital adrenal hyperplasia?
What is the primary hormonal deficiency in the salt-wasting form of congenital adrenal hyperplasia?
What is the primary hormonal deficiency in the salt-wasting form of congenital adrenal hyperplasia?
What physiological effect results from the absence of negative feedback in the hypothalamic-pituitary-adrenal axis in CAH?
What physiological effect results from the absence of negative feedback in the hypothalamic-pituitary-adrenal axis in CAH?
Which of the following symptoms is likely associated with cortisol deficiency in CAH?
Which of the following symptoms is likely associated with cortisol deficiency in CAH?
What is a consequence of increased androgen production in females with congenital adrenal hyperplasia?
What is a consequence of increased androgen production in females with congenital adrenal hyperplasia?
Which treatment is essential for managing congenital adrenal hyperplasia effectively?
Which treatment is essential for managing congenital adrenal hyperplasia effectively?
What cardiac issue can arise from aldosterone deficiency in congenital adrenal hyperplasia?
What cardiac issue can arise from aldosterone deficiency in congenital adrenal hyperplasia?
What is the first product formed when cholesterol is converted during steroid hormone synthesis?
What is the first product formed when cholesterol is converted during steroid hormone synthesis?
Which enzyme is directly responsible for the conversion of pregnenolone to progesterone?
Which enzyme is directly responsible for the conversion of pregnenolone to progesterone?
Where does the hydroxylation of progesterone occur to produce 11-deoxycorticosterone?
Where does the hydroxylation of progesterone occur to produce 11-deoxycorticosterone?
Which step in steroid hormone synthesis is considered the rate-limiting step?
Which step in steroid hormone synthesis is considered the rate-limiting step?
Which of the following statements about steroid hormones is correct?
Which of the following statements about steroid hormones is correct?
What is the final product of the steroid synthesis pathway starting from progesterone that involves 17α-hydroxylase?
What is the final product of the steroid synthesis pathway starting from progesterone that involves 17α-hydroxylase?
Which enzyme is involved in the conversion of corticosterone to aldosterone?
Which enzyme is involved in the conversion of corticosterone to aldosterone?
What is required for the activity of cytochrome P450 enzymes during steroid synthesis?
What is required for the activity of cytochrome P450 enzymes during steroid synthesis?
Which of the following is a product of hydroxylation at C-21 of progesterone?
Which of the following is a product of hydroxylation at C-21 of progesterone?
Which modification occurs to pregnenolone to form progesterone during steroid synthesis?
Which modification occurs to pregnenolone to form progesterone during steroid synthesis?
What happens to sodium levels in the condition associated with 17α-hydroxylase deficiency?
What happens to sodium levels in the condition associated with 17α-hydroxylase deficiency?
What is a common genetic characteristic of patients with 3β-OH dehydrogenase deficiency?
What is a common genetic characteristic of patients with 3β-OH dehydrogenase deficiency?
What is the primary clinical consequence of virtually no cortisol production in individuals with 21α-hydroxylase deficiency?
What is the primary clinical consequence of virtually no cortisol production in individuals with 21α-hydroxylase deficiency?
What is the impact of 21α-hydroxylase deficiency on hormone levels?
What is the impact of 21α-hydroxylase deficiency on hormone levels?
Which statement accurately describes the syndrome associated with 3β-OH dehydrogenase deficiency?
Which statement accurately describes the syndrome associated with 3β-OH dehydrogenase deficiency?
In patients with 17α-hydroxylase deficiency, what effect does excess mineralocorticoid production have?
In patients with 17α-hydroxylase deficiency, what effect does excess mineralocorticoid production have?
What differentiates the classic form of CAH from the non-classic forms?
What differentiates the classic form of CAH from the non-classic forms?
What is a major consequence of congenital adrenal hyperplasia in both sexes?
What is a major consequence of congenital adrenal hyperplasia in both sexes?
Which zone of the adrenal cortex is primarily responsible for synthesizing aldosterone?
Which zone of the adrenal cortex is primarily responsible for synthesizing aldosterone?
Which of the following enzyme deficiencies is associated with the overproduction of adrenal androgens?
Which of the following enzyme deficiencies is associated with the overproduction of adrenal androgens?
What clinical manifestation in infants may suggest the presence of congenital adrenal hyperplasia?
What clinical manifestation in infants may suggest the presence of congenital adrenal hyperplasia?
Which mechanism best describes how steroid hormones exert their effects on target cells?
Which mechanism best describes how steroid hormones exert their effects on target cells?
How does the deficiency of aldosterone affect an individual's electrolyte balance?
How does the deficiency of aldosterone affect an individual's electrolyte balance?
What is one consequence of the overproduction of androgens in females suffering from CAH?
What is one consequence of the overproduction of androgens in females suffering from CAH?
Which hormone regulates blood pressure and fluid balance through its effects on the kidneys?
Which hormone regulates blood pressure and fluid balance through its effects on the kidneys?
What is the primary impact of glucocorticoids like cortisol on metabolism?
What is the primary impact of glucocorticoids like cortisol on metabolism?
What condition results from the accumulation of steroid hormones due to enzymatic deficiencies in their synthesis pathways?
What condition results from the accumulation of steroid hormones due to enzymatic deficiencies in their synthesis pathways?
Flashcards
Hydroxylation
Hydroxylation
The process of adding a hydroxyl group (-OH) to a molecule. This changes the molecule's chemical structure and properties. It's often catalyzed by enzymes like the cytochrome P450 family.
21α-hydroxylase
21α-hydroxylase
An enzyme that catalyzes the addition of a hydroxyl group to the 21st carbon of progesterone.
Oxidation
Oxidation
A process where a molecule, atom, or ion loses electrons. In biochemistry, it often involves adding oxygen or removing hydrogen atoms.
18-Hydroxydehydrogenase
18-Hydroxydehydrogenase
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Hydroxyl group
Hydroxyl group
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18-Hydroxylase
18-Hydroxylase
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11-beta-hydroxylase (CYP11B1)
11-beta-hydroxylase (CYP11B1)
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How steroid hormones act
How steroid hormones act
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11-beta-hydroxylase (CYP11B2)
11-beta-hydroxylase (CYP11B2)
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Hormone Response Elements (HREs)
Hormone Response Elements (HREs)
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Steroid hormones
Steroid hormones
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Glucocorticoids
Glucocorticoids
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Cortisol
Cortisol
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Mineralocorticoids
Mineralocorticoids
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What are steroid hormones?
What are steroid hormones?
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Describe the process of steroid hormone synthesis.
Describe the process of steroid hormone synthesis.
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What is StAR and what is its role in steroid hormone synthesis?
What is StAR and what is its role in steroid hormone synthesis?
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How is pregnenolone produced during steroid hormone synthesis?
How is pregnenolone produced during steroid hormone synthesis?
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How is progesterone synthesized?
How is progesterone synthesized?
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How is aldosterone synthesized from progesterone?
How is aldosterone synthesized from progesterone?
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How is cortisol synthesized from progesterone?
How is cortisol synthesized from progesterone?
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What are the key enzymes involved in steroid hormone synthesis?
What are the key enzymes involved in steroid hormone synthesis?
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What is the rate-limiting step in steroid hormone synthesis?
What is the rate-limiting step in steroid hormone synthesis?
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Congenital Adrenal Hyperplasia (CAH)
Congenital Adrenal Hyperplasia (CAH)
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21α-hydroxylase deficiency
21α-hydroxylase deficiency
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17α-hydroxylase (CYP17)
17α-hydroxylase (CYP17)
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17α-hydroxylase deficiency
17α-hydroxylase deficiency
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3β-OH dehydrogenase deficiency
3β-OH dehydrogenase deficiency
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Salt-wasting Form of CAH
Salt-wasting Form of CAH
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Non-Classic Form of CAH
Non-Classic Form of CAH
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What is CAH with 11-β-hydroxylase Deficiency?
What is CAH with 11-β-hydroxylase Deficiency?
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What are the Hormonal Effects of 11-β-hydroxylase Deficiency?
What are the Hormonal Effects of 11-β-hydroxylase Deficiency?
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What are the Clinical Effects of Cortisol Deficiency in CAH with 11-β-hydroxylase Deficiency?
What are the Clinical Effects of Cortisol Deficiency in CAH with 11-β-hydroxylase Deficiency?
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What are the Clinical Effects of Aldosterone Deficiency in CAH with 11-β-hydroxylase Deficiency?
What are the Clinical Effects of Aldosterone Deficiency in CAH with 11-β-hydroxylase Deficiency?
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What are the Effects of Androgen Excess in CAH with 11-β-hydroxylase Deficiency?
What are the Effects of Androgen Excess in CAH with 11-β-hydroxylase Deficiency?
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What are the Effects of Lack of Negative Feedback in CAH?
What are the Effects of Lack of Negative Feedback in CAH?
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Study Notes
Biochemical Synthesis of Steroid Hormones
- Steroid hormones are derived from cholesterol.
- The synthesis of steroid hormones occurs in the adrenal cortex and gonads.
- The adrenal cortex has three distinct zones: glomerulosa, fasciculata, and reticularis. Each zone produces different types of steroid hormones.
- The adrenal medulla produces catecholamines (adrenaline and noradrenaline).
- Steroid hormones are lipid-soluble, so they diffuse across cell membranes.
- They bind to intracellular receptors in the cytoplasm or nucleus, and bind to DNA triggering the transcription of a target gene to mRNA.
- There are hormone response elements within the DNA sequence, located near the transcription initiation site.
- These elements bind to the activated steroid hormone-receptor complex, which in turn affects the expression of target genes.
Learning Objectives
- The biochemical pathway of glucocorticoid and mineralocorticoid synthesis from cholesterol is described.
- The key enzymes involved in each pathway are differentiated.
- The mechanism of action for steroid hormones is clarified.
- The impact of deficiencies in these hormones, leading to congenital adrenal hyperplasia (CAH), is outlined.
- How these deficiencies result in congenital adrenal hyperplasia (CAH) is outlined.
Congenital Adrenal Hyperplasia (CAH)
- Inherited autosomal recessive disorders.
- Mutations in the genes encoding enzymes involved in mineralocorticoid.
- Glucocorticoids or sex steroids synthesis.
- Enlarged adrenal glands (hyperplastic adrenomegaly) result.
- Reduced levels of cortisol or aldosterone result with overproduction of androgen.
Clinical Presentation of Classic CAH
-
(In Infants):*
-
Ambiguous genitalia in females.
-
Enlarged genitalia in males.
-
Poor weight gain.
-
Adrenal crisis (dehydration, vomiting, hypoglycemia, and circulatory collapse)
-
(In Children and Adults):*
-
Early onset of puberty.
-
Rapid growth during childhood.
-
Premature completion of growth (short stature).
-
Irregular menstrual cycles.
-
Infertility in both sexes.
Classification of Steroid Hormones
- Steroids:
- Adrenal Cortical Hormones (Corticoids)
- Glucocorticoids (e.g., cortisol)
- Mineralocorticoids (e.g., aldosterone)
- Sex hormones
- Female sex hormones (e.g., estrogens, progesterone)
- Male sex hormones (e.g., androgens, testosterone)
- Adrenal Cortical Hormones (Corticoids)
- Peptide hormones: (e.g., insulin, glucagon)
- Amino acid derivatives: (e.g., thyroid hormones)
Steroid Hormone Functions
- Glucocorticoids (e.g., cortisol): Regulate metabolism, mood, blood pressure, immunity, and pain sensation.
- Mineralocorticoids (e.g., aldosterone): Regulate electrolyte and fluid balance, and blood volume, and Reabsorb sodium in the kidney at the expense of potassium and H+
- Estrogens and Progesterone: Female secondary sexual characteristics, regulation of the menstrual cycle, regulation ovulation, maintains pregnancy.
- Androgens (e.g., testosterone): Male reproductive development
Metabolic Functions of Glucocorticoids
- Carbohydrate Metabolism: Stimulates hepatic gluconeogenesis, increases glycogen deposition in the liver, and antagonizes the peripheral action of insulin on glucose uptake.
- Protein Metabolism: Inhibits amino acid uptake and protein synthesis in extrahepatic tissues, is a potent protein catabolic agent in peripheral tissues (muscle, skin, and bone), and stimulates amino acid uptake by the liver for gluconeogenesis.
- Fat Metabolism: Increases the mobilization of fatty acids, stimulates lipolysis in adipose tissue, and increases fat deposition in facial and truncal areas
Actions of Mineralocorticoids
- Secreted in response to increased extracellular fluid (ECF) and high potassium (K+) concentration.
- Stimulates the transcription of the sodium-potassium ATPase.
- Increases the number of sodium pumps in the basolateral membranes of tubular epithelial cells.
- Facilitates sodium (and water) uptake from the tubular lumen.
- Reabsorbs sodium in the kidney at the expense of potassium and H+.
Disorders of Adrenal Gland Insufficiencies: Congenital Adrenal Hyperplasia (CAH)
- Autosomal recessive disorders of cortisol biosynthesis resulting in failure of cortisol secretion and loss of negative feedback to the hypothalamic-pituitary-adrenal (HPA) axis.
- Classified based on the specific enzyme step involved.
- 3β-hydroxysteroid dehydrogenase deficiency
- 17α-hydroxylase deficiency
- 21-hydroxylase deficiency
- 11β-hydroxylase deficiency
Deficiency in 3β-OH dehydrogenase
- Virtually no glucocorticoids, mineralocorticoids, active androgens or estrogens.
- Salt excretion in urine
- Affected genetic males (46, XY) have ambiguous genitalia.
- Autosomal recessive.
Deficiency in 17α-hydroxylase
- Virtually no sex hormones or cortisol are produced.
- Increased production of mineralocorticoids causes sodium and fluid retention, leading to hypertension.
- Genetic males (46, XY) have female-like genitalia.
Deficiency in 21-α-hydroxylase
- Partial and virtually complete deficiencies are known.
- Classic form: deficiency in the production of mineralocorticoids and glucocorticoids. Salt wasting severe; with virtually absent mineralocorticoids and glucocorticoids.
- Non-classic form: mineralocorticoids might be normal to slightly reduced, while glucocorticoids can be deficient to varying degrees.
- Overproduction of androgens leads to masculinization of external genitalia in females and early virilization in males.
Deficiency in 11β-hydroxylase
- Decrease in serum cortisol, aldosterone and corticosterone.
- Increased production of deoxy-corticosterone causing fluid retention
- Hypertension and hypokalemia.
- Overproduction of androgens leads to masculinization of external genitalia in females and early virilization in males.
Clinical Effects of CAH
- (Cortisol deficiency):*
- Poor response to stress.
- Hypoglycemia.
- Hyperpigmentation.
- (Aldosterone deficiency):*
- Hyperkalemia.
- Hyponatremia.
- Disturbances in cardiac rhythm.
- Hypotension.
- (Combined deficiency):*
- Vascular collapse, shock, and death.
Clinical Effects of CAH (Additional Notes)
- Absence of negative feedback to the hypothalamus.
- Overproduction of ACTH
- Adrenal hyperplasia.
- Excess androgen production causing masculinization of external genitalia in females.
- Absence of active androgens results in female-like genitalia.
Treatment for CAH
- Daily glucocorticoid and mineralocorticoid replacement.
- Restore volume, electrolyte, and glucose imbalances.
Hormone Synthesis Summary
- Shortening of cholesterol hydrocarbon tail.
- Hydroxylation of steroid nucleus.
- Cytochrome P450 (CYP) mixed function oxidases.
- NADPH and oxygen are required.
- Modification occurs in endoplasmic reticulum (ER) and mitochondria of adrenal gland, ovary, and testes
First Step in Steroid Synthesis
- StAR (steroidogenic acute regulatory protein) controls the uptake of cholesterol into mitochondria.
- Cholesterol is converted to pregnenolone, catalyzed by cytochrome P450 side chain cleavage enzyme (CYP11A1).
- NADPH and oxygen are required.
Progesterone Synthesis from Pregnenolone
- 3β-hydroxysteroid dehydrogenase oxidises the 3-hydroxyl group to a 3-keto group.
- Δ5,4 isomerase isomerises the Δ5 double bond to a Δ4 double bond.
References
- Provided in the document.
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Description
This quiz covers the biochemical synthesis pathways of steroid hormones derived from cholesterol. It explores the role of the adrenal cortex and gonads in hormone production, detailing the three zones of the cortex and the mechanisms of hormone-receptor interactions affecting gene expression.
