Aromatase Is Important

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-Definition:

Androstenedione and testosterone are converted into estrone and estradiol, respectively, by the activity of aromatase, an enzyme located inside several cell types of the gonads. The catalytic active complex is composed of a cytochromeP450 aromatase. The gene encoding this protein is CyP19 and depending on the tissue and species, the aromatase possesses between 490 and 525 amino acids.
Steroid hormones, once synthesized, are secreted to the general circulation or lymphatic system to be transported and then specifically captured by their respective target organs.
When released into circulation, gonadal steroids bind to plasma proteins. The first fact is the passage of the steroid in its free form (free of its transporting protein) into the cell. Since steroid hormones are liposoluble, they are able to diffuse into and out of cells.
Consequently, most of the effects of estrogens on their target organs are due to the cascade of cellular events known as “estrogenic signaling” which is a pathway of cellular transduction that begins with the activation of estrogen receptors.
These receptors are transcription factors that are classified within class II of the family of nuclear receptors to steroid hormones . In the absence of ligand, estrogen receptors remain inactive.
The causality of the relationship between a low concentration of testosterone and increased body fat was initially proposed in the hypothesis of hypogonadism-obesity cycle. Testosterone is also converted to estradiol (E2) by the enzymatic activity of aromatase in adipose tissue.

-Discussion:

Aging and high levels of physical, chemical (environmental xenoestrogens) and emotional stress are associated with the loss of progesterone in women and testosterone in men. The process of converting androgenic hormones to estrogen is called aromatization. Aromatization leads to a dominant estrogen state which is an important factor in many common health problems.
Estrogen is a catabolic hormone (except in bone mass), which breaks down muscle mass and leads to an increase in body fat and aromatase. Testosterone and progesterone to in lesser extent are anabolic hormones that promote body mass.
Aromatase is an enzyme found in estrogen-producing cells in the adrenal glands, ovaries, placenta, testicles, brain, and fatty tissue. Higher levels of aromatase in the body convert more testosterone and progesterone to estrogen.
Increased aromatase expression in adipocytes (fat cells) results in the consequent reduction of circulating testosterone. Testosterone deficiency promotes an increase in the number of adipocytes through the stimulation of pluripotential stem cells.
And therefore increase fat deposits, through increased activity of lipoprotein lipase, which gradually produces a greater decrease in testosterone levels.
Additionally, the negative feedback that testosterone normally exerts on the hypothalamus-hypophysis axis also occurs through its aromatization to E2, centrally in the peripheral adipose tissue.
Therefore, the excess of aromatase activity by the increase in the number of adipocytes in obese men results in the suppression of testosterone secretion mediated by gonadotropins favoring the progress of hypogonadism.
The hypogonadism-obesity-adipocytokines hypothesis affects the above hypothesis and explains why the body cannot respond to low testosterone levels with compensatory androgen production through increased secretion of gonadotropins.
E2 and inflammatory adipocytokines, tumour necrosis factor α (TNFα) and interleukin 6 inhibit the hypothalamic production of GnRH and consequently the release of LH and FSH by the pituitary gland, causing a state of hypogonadotropic hypogonadism.
Leptin, a hormone derived from adipose tissue with a well known role in regulating body weight and food intake under normal conditions, also induces the release of LH through stimulation of hypothalamic GnRH neurons. GnRH neurons, however, exhibit few leptin receptors.
Kisspeptins are peptides secreted by specific neurons in the hypothalamus and can provide the functional link between leptin and gonadal regulation as they play a central role in the modulation of GnRH secretion and subsequent release of LH.
GnRH neurons possess the kisspeptin receptor and kisspeptin neurons express the leptin receptor. In obese humans, adipocytes produce high amounts of leptin and the hypothalamus-hypophysis axis becomes resistant to leptin.
Additionally, E2 receptors are present in kisspeptin neurons and there is evidence that leptin resistance, inflammation and estrogens inhibit the neuronal release of kisspeptins.
Leptin also directly inhibits the stimulating action of gonadotropins on the Leydig cells of the testicle by decreasing testosterone production. Therefore, elevated levels of leptin in obesity can decrease the level of androgens.

-Conclusion:

Testosterone deficiency is associated with a decrease in muscle mass, and muscle mass is inversely associated with insulin resistance and pre-diabetes. 70% of insulin sensitivity in the body takes place in muscle, and low testosterone levels can promote insulin resistance through metabolic effects in muscle.
The beneficial influence of testosterone on adipogenesis has also been demonstrated by investigating the direct effects of testosterone on stem cells, testosterone stimulates the development of myocyte (muscle) cells rather than adipocyte cells. In contrast, testosterone deficiency promotes the development of adipocytes (fat cells) over myocytes.
In summary, testosterone can have beneficial effects on the prevention of the pathogenesis of obesity because it inhibits adipogenesis, decreases the uptake and storage of triglycerides, influences the function of lipoprotein lipase and can reduce fat mass as well as increase muscle mass.
This in turn can have a direct effect on circulating fatty acids, adipocytokine secretion and insulin resistance. On the other hand, hyperestrogenism apart from facilitating the possibility of hypogonadotropic hypogonadism and producing sexual dysfunction and infertility, can also cause gynecomastia.

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