Endogenous oestrogens

F8. Fotsis, T., Zhang, T., Pepper, M. S., Adlercreutz, H., Montesano, R., Nawroth, P. P., and Schwergerer, L., The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature (London) 368, 237-239 (1994). 

Clomiphene is a nonsteroidal agent with oestrogenic and anti-oestrogenic properties. The mechanism of action is not precisely clear, but it ultimately leads to the release of the pituitary gonadotropins FSH and LH. It stimulates ovulation in anovulatory or oligo-ovulatory women with adequate endogenous oestrogen activity and an intact hypothalamic-pituitary-ovarian axis. 

Scragg RK, McMichael AJ, Seamark RF. Oral contraceptives, pregnancy, and endogenous oestrogen in gall stone disease—a case-control study. BMJ (Clin Res Ed) 1984 288(6433) 1795-9. 

Ethinyloestradiol, or its methylated derivative mestranol, is a satisfactory first choice for pharmacotherapy. The weaker endogenous oestrogens, oestradiol, oestrone or the conjugated equine oestrogens are preferable for physiological replacement. It remains uncertain whether all oestrogens have exactly similar hormonal and nonhormonal effects, including adverse effects. 

The endogenous oestrogens, for instance estrone and 17P-estradiol are observed to be interconvertible biochemically in the presence of the specific enzyme estradiol dehydrogenase and... 

Oestrogenic activity is not limited to mammalian steroid hormones. In addition to endogenous oestrogens (hormones), a number of exogenous compounds present in foods of plant origin as natural components or substances that get into the food as contaminants (mould metabolites, pesticides and some other substances), also possess oestrogenic activity. These substances resemble the effect of sex hormones and induce oestrus as seen in experimental animals. 

Oestrogens are both useful and harmful for the organism. An endogenous oestrogen of mammals is oestradiol, which is essential for normal development and reproduction of the organism, and also affects other important processes related to the immune system and central nervous system. At the same time, however, oestradiol is associated with cancers of the mammary glands, rectum and probably also the prostate. 

Although oestrogens do not cause vitamin Bg deficiency, the administration of vitamin Bg supplements has beneficial effects on some of the side effects of both administered and endogenous oestrogens. The supplements act in two main areas in normalizing glucose tolerance and as an antidepressant. 

Figure 13.1 The distribution of (a) chemical classes and (b) binding activity for the NCTR dataset. The oestrogen receptor binding activity is represented as RBA. The RBA for the endogenous ligand, 17p-estradiol, was set to 100.

CYP enzymes are a large and diverse superfamily of haemoproteins. Primarily membrane-associated proteins, they are located in the inner membrane of mitochondria and the endoplasmic reticulum of cells, and metabolise thousands of endogenous and exogenous compounds. Most of these enzymes can metabolise multiple substrates, and many can catalyse multiple reactions. While prevalent in the liver, CYP enzymes are also present in most other tissues of the body, and play an important role in hormone synthesis and breakdown (including oestrogen and testosterone synthesis and metabolism), cholesterol synthesis and vitamin D metabolism. Hepatic CYPs are the most widely smdied. 

This has also been demonstrated in an animal study which showed that endogenous and exogenous oestrogens have a protective effect on liver fibrosis [22]. A positive effect of oestrogens on liver cirrhosis, potentially linked to the antioxidant properties of oestradiol, has also been suggested [23]. 

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