6. Hypothalamic pituitary adrenal axis

Unlike peptide hormones, steroid hormones are not stored in advance; instead, they are _____.

produced upon stimulation

What is the common chemical precursor for all steroid hormones?

Cholesterol

Which pituitary hormone specifically stimulates the synthesis of cortisol?

Adrenocorticotropic hormone (ACTH)

Which hormone stimulates the Leydig cells in the testes to produce testosterone?

Luteinizing hormone (LH)

Which hormone stimulates the granulosa cells to convert androgens to estradiol via aromatase?

Follicle-stimulating hormone (FSH)

In the adrenal cortex, which signaling molecule stimulates the synthesis of aldosterone?

Angiotensin II (or Angiotensin III)

Why can steroid hormones freely pass through cell membranes?

They are lipophilic.

Because they are water-insoluble, steroid hormones are transported in the blood bound to _____.

proteins

What is the specific transport protein for cortisol in the blood?

Corticosteroid-binding globulin (CBG)

Testosterone and estradiol are primarily transported in the blood by _____.

sex hormone-binding globulin (SHBG)

Where are the enzymes for steroid hormone synthesis primarily located within the cell?

Mitochondria and smooth endoplasmic reticulum

What protein facilitates the shuttling of cholesterol across the aqueous intermembrane space in mitochondria?

Steroidogenic acute regulatory protein (StAR)

Which specific mitochondrial membrane houses the P450scc enzyme?

Inner mitochondrial membrane

Which enzyme catalyzes the first, obligatory step in the synthesis of all steroid hormones?

P450scc (also known as desmolase or CYP11A1)

The cleavage of the cholesterol side chain occurs between which two carbon atoms?

C20 and C22

What is the first steroid molecule formed from the cleavage of cholesterol's side chain?

Pregnenolone

What are the two primary sources of cholesterol for steroidogenesis?

Acetyl-CoA (de novo synthesis) and lipoproteins

Which enzyme converts pregnenolone to progesterone in the mineralocorticoid pathway?

3\beta-hydroxysteroid dehydrogenase (3\beta-HSD)

In the biosynthesis of aldosterone, which enzyme converts progesterone to 11-deoxycorticosterone?

21-hydroxylase (CYP21A2)

Which enzyme in the zona glomerulosa is responsible for the final conversion of corticosterone to aldosterone?

Aldosterone synthase (CYP11B2)

What is the primary physiological result of increased aldosterone on the kidneys?

Increased Na^{+} and water reabsorption and increased K^{+} excretion

Which adrenal layer is specifically responsible for glucocorticoid (cortisol) biosynthesis?

Zona fasciculata

In the cortisol pathway, which enzyme converts pregnenolone to 17-hydroxypregnenolone?

17\alpha-hydroxylase (CYP17A1)

Which enzyme catalyzes the final step of cortisol synthesis from 11-deoxycortisol?

11\beta-hydroxylase (CYP11B1)

What is the approximate ratio of Cortisol to Aldosterone in the body?

Between 100:1 and 1000:1

Which inactivating enzyme in the kidneys converts cortisol into the inert steroid cortisone?

11\beta-hydroxysteroid dehydrogenase type 2 (11\beta-HSD2)

In the liver and adipose tissue, which enzyme converts cortisone back into active cortisol?

11\beta-hydroxysteroid dehydrogenase type 1 (11\beta-HSD1)

What are the two main hypothalamic regulators of ACTH secretion?

Corticotropin-releasing hormone (CRH) and Antidiuretic hormone (ADH/vasopressin)

Where in the hypothalamus are CRH and ADH synthesized for HPA axis regulation?

Paraventricular nucleus

CRH stimulates ACTH synthesis and secretion by acting through which signaling pathway?

G_{s} protein \rightarrow increased cAMP

ADH enhances the action of CRH by acting on which specific receptor type?

V_{1b} (or V1) receptor

What is the 285-amino acid precursor protein for ACTH, \alpha-MSH, and \beta-endorphin?

Pro-opiomelanocortin (POMC)

Which POMC-derived peptide stimulates lipolysis and fatty acid mobilization?

\beta-lipotropin (\beta-LPH)

Which endogenous opioid peptide is produced during prolonged aerobic exercise, leading to a 'runner's high'?

\beta-endorphin

ACTH biological activity is primarily contained within which portion of its 39-amino acid chain?

The N-terminal 24 amino acids

At what time of day does ACTH secretion normally peak according to the circadian rhythm?

Morning (\approx 6-8 a.m.)

What is the typical half-life of ACTH in the plasma?

Approximately 10 minutes

ACTH binds to which specific membrane receptors in the adrenal cortex?

MC2 receptors

What is the rapid (within 3 minutes) effect of ACTH on the adrenal cortex?

Cholesterol mobilization and activation of cholesteryl esterase

What is the chronic effect of ACTH on the adrenal cortex?

Increased transcription of steroidogenic enzymes and a trophic effect on the cortex

Which enzyme converts angiotensinogen into the inactive decapeptide angiotensin I?

Renin

Where is the Angiotensin-converting enzyme (ACE) primarily located?

Lungs (endothelium)

How does Angiotensin II stimulate aldosterone synthesis in the zona glomerulosa?

Binding to G_{q}-coupled receptors \rightarrow increased IP_{3} and Ca^{2+}

How does cortisol affect carbohydrate metabolism in the liver?

It increases gluconeogenesis.

What is the effect of cortisol on glucose uptake in peripheral tissues?

It decreases glucose uptake, leading to insulin resistance.

How does cortisol affect protein metabolism in skeletal muscle?

It decreases protein synthesis and increases protein catabolism.

Cortisol acts synergistically with which two other hormones to increase blood glucose?

Glucagon and Growth hormone

What cardiovascular effect does cortisol have regarding catecholamines?

It increases sensitivity to catecholamines, leading to increased blood pressure.

Chronic excess of cortisol increases the risk of which bone disorder?

Osteoporosis (via decreased bone formation and increased resorption)

How does cortisol affect the immune system?

It has an immunosuppressive and anti-inflammatory effect.

What is the characteristic distribution of adipose tissue in chronic cortisol excess?

Central (abdominal) obesity

What are the three hallmark metabolic findings in Addisonian crisis?

Hyponatremia, hyperkalemia, and hypoglycemia

What is the primary cause of hyperpigmentation in primary adrenal insufficiency (Addison's disease)?

Increased ACTH (and consequently MSH) due to loss of negative feedback

Primary adrenal insufficiency is also known as _____ disease.

Addison's

In Addison's disease, the lack of which hormone leads to dehydration and hypotension?

Aldosterone

What is the most common enzyme deficiency in Congenital Adrenal Hyperplasia (CAH)?

21-hydroxylase deficiency

In CAH, why is there a compensatory increase in ACTH?

There is a lack of negative feedback due to blocked cortisol synthesis.

What is the clinical consequence of the 'diversion' of steroidogenesis toward androgens in CAH?

Virilization (e.g., genital abnormalities in females, early puberty signs)

What is the term for the characteristic facial appearance in Cushing syndrome?

Moon face (facies lunata)

What is the likely diagnosis for a patient with high cortisol that is NOT suppressed by dexamethasone and has elevated ACTH?

ACTH-dependent Cushing syndrome (e.g., Cushing disease/pituitary adenoma)

Why do patients with Cushing syndrome have 'matchstick legs'?

Muscle atrophy caused by increased proteolysis.

Which condition is defined specifically by a pituitary adenoma secreting excess ACTH?

Cushing disease

What happens to the HPA axis during exogenous glucocorticoid administration?

The axis is suppressed.

Which enzyme converts cholesterol to pregnenolone?

Desmolase (CYP11A1)

What are the three main end-products of the zona glomerulosa, fasciculata, and reticularis respectively?

Aldosterone, Cortisol, and Androgens

In the adrenal gland, catecholamines are secreted by the _____.

adrenal medulla

Which enzyme is deficient if a newborn presents with salt-wasting, hyponatremia, and hyperkalemia?

21-hydroxylase

Does cortisol increase or decrease protein synthesis in the liver?

Increases

What is the effect of acute stress on glucose supply to the brain?

Increases it (via gluconeogenesis and glycogenolysis)

Which transport protein specifically moves cholesterol from the outer to the inner mitochondrial membrane?

StAR protein

Hormonal control of steroid synthesis is strictly regulated and _____-specific.

tissue

What is the primary site of synthesis for renin?

Juxtaglomerular apparatus of the kidney

Angiotensin II is an octapeptide, meaning it consists of _____ amino acids.

8

How does cortisol affect linear growth in children?

It decreases linear growth.

What metabolic shift happens to lipids in the presence of cortisol?

Increased lipolysis (fatty acid mobilization)

Addisonian crisis is often triggered by which external factor?

Infection or stress

In Cushing syndrome, what causes the hyperglycemia?

Increased gluconeogenesis and insulin resistance

What enzyme converts 11-deoxycorticosterone to corticosterone?

11\beta-hydroxylase activity (CYP11B2)

Which hormone has weak mineralocorticoid activity at high concentrations?

Cortisol

Which peptide derived from POMC stimulates melanin synthesis?

\alpha-MSH

Is progesterone a precursor for cortisol?

Yes (it can be converted from pregnenolone)

What enzyme deficiency causes a block in both cortisol and aldosterone but an increase in androgens?

21-hydroxylase