Oestrogens metabolism

When studied by a traditional, oestrogen-metabolism bioassay method, genistein was seen to be a very weak oestrogen. Its estrogenic potency was estimated at only 10 times the potency of diethylstilboestrol. 

Progestagens with slight androgenicity medroxyprogesterone acetate Progestagens with some androgenicity and with oestrogenic metabolic products norethindrone, norethisterone acetate, lynestrenol, quin-... 

Tikkanen MJ, Aldercreute H, PuMdnen MO. Effect of antibiotics on oestrogen metabolism. EM/(1973) 1,369. 

Annas A, Carlstrcni K, Alvm G, AL-Shurbaji A The effect of ketocona le and diltiazem on oestrogen metabolism in postmenopausal women after single dose oestradiol treatment Br J Clin Pharmacol (2003) 56,334-6. 

Beckham, N. 1995, Phyto-oestrogens and compounds that affect oestrogen metabolism— Pt. 1 , Australian Jourtial of Medical Herbalism 7 11-16. 

Shutt, D.A., Weston, R.H. Hogan, J.R (1970). Quantitative aspects of phyto-oestrogen metabolism in sheep fed on subterranean clover Trifolium subterraneum, cultivar dare) or red clover Trifolium pratense). Australian Journal of Agricultural Research, 21,714-722. 

ROWLAND I, WISEMAN H, SANDERS T, ADLERCREUTZ H and BOWEY E (1999) Metabolism of oestrogens and phytoestrogens role of the gut microflora. Biochem Soc Trans. 27 (2) 304-8. 

The follicular granulosa cells are the major site of synthesis of female steroid sex hormones the oestrogens. P-Oestradiol represents the principal female follicular oestrogen. Oestriol is produced by the placenta of pregnant females. Oestriol and oestrone are also produced in small quantities as products of P-oestradiol metabolism. 

Zinedine A, Soriano JM, Molto JC, Jordi Manes J (2007) Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone an oestrogenic mycotoxin. Food Chem Toxicol 45 1-18... 

For the last forty years, many reports have emerged on the hormone-like effects of chemical compounds such as pesticides and industrial chemicals upon wildlife and humans. The effects of these materials are believed to be either direct or indirect. Direct effects involve positive or negative interactions with the hormone receptors. Indirect effects may result when the synthesis of hormones or their receptors is altered, or the transport, metabolism, or elimination of hormones is modified in some way. The discovery of hormone-like properties of some compounds was made long after their release into the environment. It was shown soon after their introduction that aviation crop dusters handling DDT had low sperm counts and workers at a plant producing the insecticide kepone were reported to have low libido, sperm counts and to be impotent. Subsequently, experiments conducted in laboratory animals demonstrated unambiguously the oestrogenic activity of these pesticides. 9 refs. 

There seems to be no metabolic control exerted on hepatic 25-hydroxylase and so all of the available cholecalciferol is converted. Hydroxylation in the kidney however is an important control point being regulated by PTH, and indirectly therefore by calcium and phosphate concentrations. Stimulation of la-hydroxylase by PTH is via a cyclic AMP (cAMP) -dependent mechanism and longer-term regulation of the activity of this enzyme is via induction mediated by other hormones such as oestrogens, cortisol and growth hormone. Typically, the plasma concentration of 1,25 dihydroxy vitamin D is in the range 20-60 ng/1, that is approximately 1000-times lower than that of its precursor. 

A deficiency of liver function reduces metabolism of steroid hormones so that the blood concentration of oestrogens in men is increased. 

Q64 Initiating carbamazepine therapy in a patient receiving oral contraceptives decreases the contraceptive effect. Carbamazepine decreases the metabolism of oestrogens and progestogens. 

Corbamazepine interacts with oral contraceptives. Corbamazepine increases the metabolism of oestrogens and progestogens resulting in a decrease in the plasma concentration of oestrogens and progestogens. This in turn brings about a decrease in the contraceptive level provided. 

Furthermore, the metabolism of isoflavones is influenced by different components of the diet. A high fiber diet may increase the growth and/or activity of bacteria responsible for equol production in the colon [90]. This is relevant since equol has an oestrogenic potency higher than the precursor daidzein [91]. 

Figure 6.28 Metabolism of diethylstilboestrol via an epoxide intermediate. This potentially reactive intermediate may show an affinity for the estradiol receptor and thereby accumulate in oestrogen target organs. This may facilitate reaction with DNA in these organs. Source. From Ref. 10.

However, the binding affinities of 197,206 and 207 [0.3%, 0.1% and <0.01%, respectively, relative to oestradiol (100%)] for the oestrogen specific acceptor protein of the rat uterus suggest that a steric or an electronic effect, rather than metabolic instability, is responsible for the absence of oestrogenic activity in these compounds. But a clear answer cannot be given because biological data of the direct 6,6-dimethyl-6-carba-analogues are not known so far. 

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