Diabetes Alters Aromatase Enzyme Levels in Sciatic Nerve and Hippocampus Tissues of Rats

Abstract

Diabetes mellitus (DM) is associated with increased risk of impaired cognitive function. Diabetic neuropathy is one of the most common and important complications of DM. Estrogens prevent neuronal loss in experimental models of neurodegeneration and accelerate nerve regeneration. Aromatase catalyzes the conversion of androgens to estrogens and expressed in a variety of tissues including neurons. Although insulin is known to regulate the activity of aromatase there is no study about the effects of diabetes on this enzyme. Present study was designed to investigate the effects of experimental diabetes on aromatase expression in nervous system. Gender-based differences were also investigated. Rats were injected with streptozotocin to induce diabetes. At the end of 4 and 12 weeks sciatic nerve and hippocampus homogenates were prepared and evaluated for aromatase proteins. Aromatase expressions in sciatic nerves of both genders were decreased in 4 weeks of diabetes, but in 12 weeks the enzyme levels were increased in females and reached to control levels in male animals. Aromatase levels were not altered in hippocampus at 4 weeks but increased at 12 weeks in female diabetic rats. No significant differences were observed at enzyme levels of hippocampus in male diabetic rats. Insulin therapy prevented all diabetes-induced changes. In conclusion, these results indicated for the first time that, DM altered the expression of aromatase both in central and peripheral nervous systems. Peripheral nervous system is more vulnerable to damage than central nervous system in diabetes. These effects of diabetes differ with gender and compensatory neuroprotective mechanisms are more efficient in female rats.

Gender differences in cognitive deficits in schizophrenia with and without diabetes

“…The results support that the neuronal protective effects of estrogen may also play an important role in the female individuals who showed fewer cognitive deficits than males. This finding is also supported by a series of other studies [41][42][43][50][51][52]. However, some studies have failed to find that estrogen has significant protective effects for cognitive function in females rather than males with diabetes only [29,33].…”

“…Several studies have indicated that poorer glycemic control and higher HbA1c are significantly associated with cognitive deficits [21,23,[41][42][43][44][45]. Studies have also shown that female individuals with diabetes have poorer glycemic control and a higher HbA1c concentration than males [24].…”

Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

“…For instance, the expression of aromatase is altered by long-term diabetes in a sex specific way. Indeed, the expression of this enzyme is increased in the sciatic nerve of female but not of male rats (Burul-Bozkurt et al, 2010).…”

Role of sex hormones in diabetic nephropathy

“…This results in the conversion of testosterone and androstenedione to estradiol and estrone, respectively, which contribute to reducing serum testosterone concentrations in men with diabetes (42)(43)(44)(45)(46)(47). In addition, the disruption of glucolipid metabolism, the reduced bioavailability of insulin during diabetes and the reduced activity of CYP19 in the ovaries of diabetic rats, as determined by Bozkurt et al, might be responsible for the reduced levels of estradiol in females with diabetes (48)(49)(50).…”