A QUESTION TO CHECK IF UR GONNA ACE STEP 1 OR NOT!!!!

[krishna1033]

HI,
MY FIRST POST HERE AND I WANNA START HERE WITH THE Q WHICH I THOUGHT WAS THE TOUGHEST Q THAT I EVER SAW IN MY STEP 1 PREP.
it is an integrated basic science q that covers a fair bit of pharmacology,physiology and pathology,
here is the q followed by some clues!.
two rules in answerin the q
1.if you have answered this q in our online study group or anywhere else,plz do not answer.
2.try to answer without any books or websites as reference at first.

here is the q!.much ado about nothin????????. :D :) :evil:


The mineralocorticoid receptor (MR) displays the same affinity [in fact

some books say thrice the affnity!!!!!] for glucocorticoid hormones as it

does for the hormone that is in excess in conn's syndrome. The sensitivity

of the MR to this hormone depends on which of the following enzymes?

A. AIdosterone synthase
B. C17,20-Iyase
C. 11-beta hydroxysteroid dehydrogenase type 2 (HSD2)
D. Na+/K+-ATPase
E. 17-alpha hydroxylase
F. 11-beta hydroxysteroid dehydrogenase type 4 (HSD4)

two clues if u havent figured it out!.
1,the mechanism of a rare disease called APPARENT MINERALOCORTICOID EXCESS[AME] is a defect of this enzyme.

2.have you heard of the drug CARBENOXOLONE??????.it is an anti PUD drug.one of the side effects of this drug is volume retention .the mechanism of this side effect is related to this enzyme mentiuo9ned in the q above!.
more clues if want!!!!!!!.
q esp for mohd **** butta and pingdeng both of whom have been a source of inspiration for me!.
btw,when does the chat here happen?regular?.lemme know.
ur on ur way to acing if u can get this q!!!!!!!!!!!
g murali krishna

[Anonymous]

My guess is C. renal 11 -hydroxysteroid dehydrogenase. thanks for the clues.

[Anonymous]

I rather think the ans is A. aldosterone synthase..

which is present only in z glomerulosa (hence aldosterone prd only in this area)....lack of this hormone would lead to increased glucocorticoid production...and mineralocorticoid response due to glucocorticoids...

????/

[krishna1033]

REFER GANONG ENDOCRINOLOGY FOR SOME MORE CLUES!!!!!!!!

[Anonymous]

My answer is F. I hope I don't get this question on the board. C looks very tempting.

[emerson24]

i think its a bit premature to say that you may not ace step one if you miss that question. Hard yes, but thats's one question.

[krishna1033]

HI GUYS,
LOOK SLIKE SOME OF U GOT THE ANS RIGHT!!!!!!!!.
CONGRATS.
FIRST OF ALL.,I DO NOT WANT TO DISCOURAGE ANYBODY BUT ONLY WANTED TO STIMUL;ATE THE INTELLECTUAL THINKING OF ALL OF US IN ENDOCRINE PHYSIOLOGY.WE ALL KNOW THAT THESE SO CALLED 'ZEBRAS' R NEVER TESTED ON STEP 1!.
JUS WANTED TO CLARIFY THAT POINT!!!!!.
HERE IS EXPLANATION!
READ ON!!!!!!!!



The correct answer is C. Mineralocorticoid receptors (MR) are members of a superfamily of steroid/thyroid/retinoid/orphan (STRO) receptors. MR are intracellular and act as ligand-activated transcription factors to regulate gene expression. The human MR is a 984 amino acid protein, and the cDNA has been cloned and sequenced. The MR shows the same affinity for aldosterone and glucocorticoids. Since the plasma concentration of cortisol is much higher than that of aldosterone, a mechanism is necessary to protect MRs from constant occupancy by glucocorticoid hormones. This mechanism depends on the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2), which converts cortisol (and corticosterone) into 11-dehydro metabolites in the endoplasmic reticulum. These are not ligands for MR. This permits the MR to be occupied by aldosterone as a function of its serum levels. In the absence of, or inhibition of HSD2, the MR will be occupied by glucocorticoids, and a permanent Na+ reabsorption will occur. This concept can be seen at work in patients with excessive ingestion of licorice. Glycyrrhizic acid, an active hypertensive component in licorice, and its derivative 18-beta-glycyrrhetinic acid, inhibit HSD2 activity. Cortisol activation of MR induces sodium retention, potassium excretion, and hydrogen ion excretion in the kidney, mimicking the symptoms of aldosteronism: hypertension, hypokalemia, and metabolic alkalosis.

Aldosterone synthase (choice A) converts a CH3 group at C18 of the steroid molecule to an aldehyde group, from whence comes the name aldosterone. This enzyme is expressed exclusively in zona glomerulosa of adrenal cortex. Aldosterone synthase is encoded by the gene CYP11B2 and has 11-beta-hydroxylase, 18-hydroxylase, and 18-hydroxy-dehydrogenase activity.
Activity of C17,20-lyase (choice B) is responsible for producing the androgens, dehydroepiandrosterone (DHEA) and androstenedione.
Na+/K+-ATPase (choice D) is located in basolateral membranes of the distal tubular cells and generates the electrochemical gradient that drives diffusion through the sodium and potassium channels. Aldosterone stimulates gene expression of mRNA for this enzyme.
The synthesis of cortisol requires 17-alpha hydroxylation of pregnenolone by 17-alpha hydroxylase (choice E), which is expressed only in the zona fasciculata.