The enzyme 17α-hydroxylase (CYP 17) is not present in the outer layer of the cortex and, thus, cortisol and androgens cannot be formed in this layer. Steroids and their metabolic by-products (notably lipid hydroperoxides) are released into the adrenal circulation and inhibit critical enzymes in subsequent layers through which the blood flows. As a result, no aldosterone can be synthesized by cells below the outer glomerulosa layer. In the inner layer, 17α-hydroxyprogesterone cannot be converted to cortisol but is shunted into the formation of androgens. Interestingly high cortisol concentrations reaching the adrenal medulla stimulate the synthesis of phenylethanolamine- N -methyltransferase which catalyzes the conversion of norepinephrine to epinephrine (see Box ). Thus, the structural relationship between the cortex and medulla and its blood supply has additional functional implications within the medulla.
The next step is to look at glucocorticoid dose. Often when a dog is first diagnosed, the vet will prescribe doses of prednisone (or other glucocorticoids) that cause side-effects such as excessive drinking and urination – often referred to by the technical term PU/PD for polyuria/polydipsia. Lowering the dose of prednisone, after your dog is properly stabilized, will often resolve this type of incontinence. If this is causing the problem for your dog, he may also be exhibiting other symptoms of too much prednisone such as excessive appetite and/or irritability.