You are absolutely right in questioning me on these points. Having wrote the
message quickly, I've realised that I've made some unforgiveable errors.
Firstly, omit any reference to renal in the zonae mentioned, this is wrong
and it should read adrenal (I must have missed off the 'ad'), well spotted.
To produce cortisol and corticosterone, 11beta-hydroxylase acts on
11-deoxycortisol and 11-deoxycorticosterone respectively.
In order to answer your third question, I need to describe the chemical
names of both cortisol and cortisone. Now, cortisol is actually 11beta,
17alpha, 21-trihydroxy-4-pregnene-3,20-dione, and cortisone is 17alpha,
21-dihydroxy-4-pregnene-3,11,20-trione. If you look at the enzyme's name
(11beta-hydroxylase), you can clearly see that its catalytic reaction
involves the hydroxylation of position 11 in the beta plane. The difference
between cortisol and cortisone is that instead of the latter having a
hydroxyl group at position 11, it has a ketone functional group instead. So,
you can obviously see that if the enzyme 11beta-hydroxylase were to convert
cortisone to cortisol and vice versa, it would have to do more than just
hydroxylate position 11, such as either removing the ketone group completely
(C=O) or breaking the pi bond (i.e. the double bond) between the C and O
atom and then adding the H atom. In any case, this would involve a lot of
bioenergy for a single enzyme to carry out on its own and therefore
11beta-hydroxylase (I think!) does not convert cortisone to cortisol and
vice versa. I am unaware of the enzymes that may carry out such a conversion
and would be interested to know the pathway (you mention 'under the
appropriate conditions' - such as?).
To provide a possible answer to your last question (about
'immunosuppression'), the papers you've obvsiouly read well do imply that
cortisol has an immunosuppressive effect. However, you must also ask
yourself this - 'is this just a result of immunosuppression or are there
other factors involved?'
I only say this because another key component of the immune system is the
inflammatory response itself! In fact, you could say that the inflammatory
response is a key 'tool' of the immune system for it to work efficiently in
removing potential pathogens. Indeed, the lipid mediators of an acute
inflammatory response (i.e. prostaglandins, leukotrienes, platelet
activating factor etc) are derived from the precursor molecule arachidonic
acid. These lipid mediators are important in that they alter microvascular
permeability and trap circulating leucocytes etc. Cortisol acts to suppress
the production of these mediators by inducing a phosphoprotein called
LIPOCORTIN (which in turn inhibits PHOSPHOLIPASE A2 the enzyme involved in
producing arachidonic acid!). So you can see that if the levels of
arachidonic acid are reduced then so are the levels of lipid mediators.
There is a lot of information regarding this phenomenom, and I suggest that
you also look up its effects on cyclooxygenase 2 (COX 2), lysosomes, nitric
oxide synthase (NOS) and inflammatory mast cells, which can be found in any
good Physiology/Endocrinology textbook. Therefore, don't forget that the
immune system relies heavily on the inflammatory rection for its efficacy
(note however, the inflammatory response can also be very harmful to the
human body - check out Multiple Sclerosis for example - and has earned the
nickname 'a double edged sword').
As for the role of corticosterone in immunosuppression in humans, I am
unsure as to the possible mechanisms, although I suggest you search journals
such as The Lancet, BMJ or The Journal of Endocrinology etc for further
Russell Farris <tryggvi at email.msn.com> wrote in message
news:#$hvzWoq$GA.342 at cpmsnbbsa04...
> Dr. Samuels,
> Thanks for the detailed response to my question. You have given me
> pointers I can use to dig out more information myself. There were a couple
> of items in your answer that puzzled me, however.
>> "Theophilus Samuels" <theophilus.samuels at btinternet.com> ...
> > Cortisol is the predominant glucocorticoid in humans (and is produced
> > the renal zona fasciculata),
>> I understood that cortisol was produced in the adrenal cortices.
> it also produced in the kidneys?
>> > The
> > enzyme 11beta-hydroxylase acts on two different molecules to give rise
> > either cortisol or corticosterone . . . .
>> What precursor does 11beta-hydroxylase act on to produce cortisol
> corticosterone? Do I remember correctly that 11beta-hydroxylase
> interconverts cortisol to cortisone, and cortisone to cortisol, under the
> appropriate conditions?
>> > Cortisol and corticosterone . . . . Are you sure you meant
> > to question their immunosuppressive qualities?
>> I have read dozens of papers and abstracts that deal with the fact
> that cortisol encourages the growth of many pathogens in humans, and
> corticosterone does likewise with animals. I'm pretty sure the term
> "immunosuppression" was often used in connection with these two hormones.
> What I have not been able to find out was whether corticosterone had a
> role in suppressing immune functions in humans.
>> I started studying Chlamydia pneumoniae a couple of years and it
> led me into fields i never dreamed of. I feel like a sixty-year old grad
>> Russ Farris