Dr. Amy Nett: Okay. So, in general, we have cortisol, which is made primarily in the adrenal glands. Cortisol is the active form. There is interconversion between cortisol and cortisone. Cortisone is the inactive form. The enzyme that converts cortisol to cortisone and vice versa, cortisone to cortisol, is called 11β-hydroxysteroid dehydrogenase. So, when we talk about things that favor cortisone, when you’re looking at that DUTCH profile and cortisone is favored, things that increase the shift of 11β-hydroxysteroid dehydrogenase to cortisone are going to be things that we mentioned such as magnolia, estradiol, scutellaria, hyperthyroidism, citrus peel extract, testosterone. Those things are all going to shift that enzyme in favor of cortisone, or at least shift the body’s favor state of cortisol into the inactive form, into cortisone, but 11β-hydroxysteroid dehydrogenase can also shift cortisone back into cortisol, and we see a preference for cortisol in some of those states such as hypothyroidism.
Licorice also inhibits 11β-HSD conversion into cortisone. We’ve said high insulin, excess sodium. That’s when we see cortisol being favored, but yes, there is interconversion. When you get into 5ɑ and 5β-tetrahydrocortisone or tetrahydrocortisone, that is irreversible, so there it’s the 5ɑ or 5β-reductase enzyme acting on cortisol or cortisone and converting those into the tetrahydrocortisone metabolites. Those are then excreted, okay?
Then, let’s see. You also asked, “There’s bound and free cortisol.” Yes. There’s a protein called corticosteroid-binding globulin. It’s also called transcortin. This protein binds cortisol and cortisone. It can also bind a few other compounds such as aldosterone. It binds a little bit of, I think, progesterone, just a small percentage, but the corticosteroid-binding globulin, yes, it also will bind cortisol and cortisone, so cortisol is not going to be active when it’s bound. These are all complicating factors when we’re trying to figure out what is going on with the cortisol picture. Hopefully that clears it up a little bit.
Precision Analytics has a chart that it gives, I think with every test now, that shows all the pathways of DHEA conversion into all the various hormones, and it shows the pathway pretty clearly, you know, DHEA to androstenedione, and going into all the different steroids. Then you can also see like the pregnenolone to progesterone to cortisol pathway. So, that might clarify things a little bit, if that was all just a lot of words coming together. It is tricky, and it sounds like you have the gist of it based on what you wrote. The only thing I would say here, that you wrote, is I would clarify cortisol and cortisone can be interconverted, but the metabolites are a one-way direction for excretion and are not converted back into active forms. Okay, so hopefully that clarifies it a little bit. That’s a lot of information.