Results of in vitro cell culture (human H295R adrenocortical carcinoma cells) studies reveal that both 21-hydroxylase and
aromatase enzymes were inhibited by melatonin. Also, in dogs with adrenal disease that are treated with melatonin, and repeat
adrenal steroid panels are done, cortisol levels are consistently reduced and estradiol levels are variably reduced.
Inhibition of the 21-hydroxylase enzyme would lower cortisol levels, and inhibition of the aromatase enzyme would lower estradiol
levels. Estradiol levels are decreased in dogs treated with melatonin. Melatonin treatment for cases of mild adrenal disease
in dogs may be effective, and particularly in cases where sex steroids are increased.
Melatonin and phytoestrogens (isoflavones, lignins, genistein) are known to inhibit 3-beta hydroxysteroid dehydrogenase. Lignins
and genistein also are known to decrease the activity of aromatase enzyme in MCF-7 cells in vitro. So, combinations of melatonin
and phytoestrogens may have efficacy in treating hyperestrinism conditions.
Hyperestrinism in dogs
Hyperestrinism in dogs may be a new and emerging disease entity. In sample submissions to the Clinical Endocrinology Service
in 2005 at the University of Tennessee, 40 percent of adrenal panels had elevated estradiol levels (>70 pg/ml). In hyperestrinism
cases, estradiol is the estrogen that is increased, ACTH stimulation and LDDS tests are usually normal for cortisol, thyroid
function is normal or controlled, liver problems are frequent and typical (very elevated serum alkaline phosphatase, hepatomegaly,
steroid hepatopathy, hyperechoic liver by ultrasound study), PU/PD is frequent, panting may be present, hair-coat problems
often are present, skin biopsy results suggest an endocrinopathy, there is no change in estradiol level in response to ACTH
stimulation or LDDS tests as currently conducted, resistance to mitotane may occur and increase often occurs in response to
Effective treatment options for hyperestrinism in dogs is limited, and drugs that could be expected to be efficacious (aromatase
inhibitors) often are limiting due to cost. Melatonin and phytoestrogen treatment may be effective for these reasons. Mitotane
likely will be effective if the source of estradiol is the adrenal tissues. Trilostane treatment frequently results in increased
estradiol levels and this may be a reason why less than effective treatment with the drug sometimes occurs.
Dr. Hoskins is owner of Docu-Tech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities
in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail: firstname.lastname@example.org