Estradiol plays a
beneficial role in the lipogenesis in both male and females , But those who are aromatase-deficient (Cyp19KO)
persons exhibit obesity and dyslipidemia , proving that estradiol
plays a beneficial role in the lipogenesis.(more fat deposition). In
the male gonad, estrogens are synthesized in the Leydig cells, Sertoli cells,
and mature spermatocytes.
Part : 2 ABC of Extra-gonadal synthesis of Oestrogens in Females
and their role in women??
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Can extragonadal synthesis
of oestrogens from androgens promote Cancer in females. However, adverse effect
of adipose tissue-driven estradiol is also indicated in the pathogenesis of
breast cancer. For instance, in a breast with a tumor, adipose tissues proximal
to the tumor exhibit higher aromatase activity than those distal to the
tumor .(See Fibroadenoma) What are then the Extragonadal organs sourcesa;-Estradiol is also produced in a number of
extragonadal organs, including the adrenal glands, brain, adipose tissue, skin, pancreas , and other
sites yet to be identified. The discoveries of extra-gonadal sites of
estradiol synthesis greatly expands our knowledge of the novel roles of
estrogens beyond the reproductive system.
How Oestrgen enters ATM Booth?? What does it do corruption / deposit cash money
at ATM_how does E2 acts in nucleus:-Like other steroid hormones, estrogens
enter passively into the cells and bind to the estrogen receptors, which then regulate the transcription
of downstream estrogen-responsive genes. Among the number of different forms of
estrogens, 17β-estradiol (estradiol) is the most common and potent form of
estrogen in mammals.
The first discovery of extra-gonadal estrogen synthesis was made
in 1974 by Hemsell and his colleagues when they made an unexpected observation that androgens were converted
to estrogens in adipose tissue . Since then, a number of other extra-gonadal
sites of estrogen synthesis have been discovered. Adipose
tissues are considered to be the major source of circulating estrogen after the
gonads in both men and women, and the contribution made by the adipose tissues
to the total circulating estrogens increases with advancing age .
The chemical structure and biological activity
of the estrogens synthesized in the extra-gonadal sites are not different from
those that are produced by the gonads. However, there are unique features that
make the extra-gonadal estrogen synthesis differ from the gonadal synthesis. A
major difference is in the biochemical pathway of estrogen synthesis. The
tissues and cells of the extra-gonadal sites of estrogen synthesis are unable
to synthesize C19 steroids, the precursors of estrogen synthesis, but are able
to convert C19 steroids to estrogens, a critical and rate-limiting step
mediated by Cyp19 aromatase.
Hence, extra-gonadal
estrogen synthesis is dependent on an external source of C19 precursors and the
level of aromatase expression. Because C19 steroids can be supplied to a local
tissue via circulation and are converted to estrogens in any tissue where
aromatase is expressed, the presence of aromatase expression in a local tissue
confirms extra-gonadal estrogen synthesis. . lists the peripheral tissues that express
aromatase and are therefore able to convert C19 precursors to estrogens.
These extra-gonadally
synthesized estrogens are thought to act and be metabolized locally, which limits
their systemic effects .. Another unique feature of extra-gonadal estrogen
synthesis is that while the total amount of estrogen synthesized in each tissue
may be small, the local tissue concentrations of estrogens could be high enough
to exert biological impact locally. The functional roles of estrogens are
mediated mostly by estrogen receptors that are nuclear receptor transcription
factors. Therefore, a tissue that expresses one or more estrogen receptors is
considered to be a target of estrogenic regulation lists key organs and
tissues that express estrogen receptors.
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