For me this article was a ray of light clarifying a number of questions about the sources of oestrogens and hormones. It is complicated and I still have to TRY and get to grips with it, but the first paragraph was an illuminating moment.
For me it raises enormous questions as to treatment protocols and illustrates the complexity of it all, and underlines how blunt some historic approaches (ablation) may prove in the furute to have been.
RB
http://erc.endocrinology-journals.or.../full/12/4/701
ABSTRACTS
Biologically active hormones are produced and secreted from the endocrine organs, transported through the circulation, and act on their target tissues where their specific receptors are expressed (Fig. 1AGo). This system is known as the endocrine system, and biological features of hormone-dependent target tissues are generally considered to be influenced by the plasma concentration of the biologically active hormones. In addition, hormones can also act in the same cell (autocrine) (Fig. 1BGo) or neighboring cells (paracrine) (Fig. 1CGo) without release into the circulation. A large proportion of androgens in men (approximately 50%) and estrogens in women (approximately 75% before the menopause, and close to 100% after the menopause) are synthesized in peripheral hormone-target tissues from abundantly present circulating precursor steroids (Labrie et al. 2003), where the enzymes involved in the formation of androgens and estrogens are expressed (Fig. 1DGo). These locally produced bioactive androgens and/or estrogens exert their action in the cells where synthesis occurs without release into the extracellular space. This phenomenon is different from the autocrine, paracrine and classical endocrine action, and is called ‘intracrine’. In classical endocrine systems, only a small amount of hormone is generally utilized in the target tissues, and thereafter the great majority is metabolized or converted to inactive forms. On the other hand, an intracrine system requires minimal amounts of biologically active hormones to exert their maximum effects. Therefore, intracrine is an efficient mode of hormone action and plays important roles especially in the development of hormone-dependent neoplasms. It is also important to note that, in an intracrine system, serum concentrations of hormones do not necessarily reflect the local hormonal activity in the target tissues.
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Figure 1 Summary of endocrine (A), autocrine (B), paracrine (C), and intracrine (D) actions. {701fig1}, inactive hormone; {701fig2}, bioactive hormone; {701fig3}, receptor; {701fig4}, promoter region of the target gene.
Sex steroids, such as estrogens and androgens, play important roles in various target tissues including reproductive organs. A majority of breast carcinoma tissues express estrogen (ER) and androgen (AR) receptors, and estrogens greatly contribute to the growth of breast cancers. Breast carcinoma tissues have been demonstrated to process intracrine activity. Locally produced biologically active estrogens act in breast carcinoma tissues. This mechanism has been considered to play a pivotal role in the proliferation of breast carcinoma cells. The blockade of this pathway potentially reduces cell proliferation of breast tumors, and it is very important to obtain a better understanding of sex steroid-related enzymes in breast carcinoma as potential therapeutic targets of endocrine therapy. Therefore, in this review we summarize the results of recent studies on the expression and regulation of the enzymes related to intratumoral production of sex steroids in human breast carcinoma tissues, and discuss the potential biological and/or clinical significance of intratumoral production of sex steroids in these carcinomas.
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