Oestrogenic steroids

Panter G.H., R.S. Thompson, N. Betesord, and J.P. Sumpter (1999). Transformation of a non-oestrogenic steroid metabolite to an oestrogenically active substance by minimal bacterial activity. Chemosphere 38 3579-3596. 

UGT activity is modulated by various hormones. Excess thyroid hormone and ethinyl oestradiol (but not other oral contraceptives) inhibit bilirubin glucuronidation. In contrast, the combination of progestational and oestrogenic steroids results in increased enzyme activity. Bihrubin glucuronidation can also be inhibited by certain antibiotics (e.g. novobiocin or gentamicin, at serum concentrations exceeding therapeutic levels) and by chronic hepatitis, advanced cirrhosis and Wilson s disease. 

Labelling with Isotopic Hydrogen.—Various oestrogenic steroids with high specific radioactivity were obtained by reduction of their 2,4-dibromo- or 2,4-iodo-derivatives with tritium gas over 5% Pd-A Oa, to give 2,4-ditritiated products." Betamethasone 17-benzoate (484) was labelled [1,2- H2] by selective reduction of... 

Oestrogens, steroidal (Suppl. 7 1987) (NB This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)... 

Malcolm, Dyson, and May, for a series of 20 oestrogenic steroids and stilbene derivatives, such as cis-stiIboestrol, stiIboestrol,... 

Intracellular steroid receptors, which alter gene expression, exist for corticosteroids, oestrogens and progesterone in the brain, as in the periphery but they cannot account for the relatively rapid depression of CNS function induced by some steroids. This was explained when Harrison and Simmonds (1984) discovered that alphaxalone (the steroid anaesthetic) potentiated the duration of GABA-induced currents at the GABAa receptor in slices of rat cuneate nucleus just like the barbiturates (Fig. 13.6). Of the... 

NAGEL s c, VOM SAAL F s, WELSHONS w V (1999) Developmental effects of oestrogenic chemicals are predicted by an in vitro assay incorporating modification of cell uptake by serum. J Steroid Biochem Mol Biol. 69 343-57. 

Applications APCI-MS is often more widely applicable than ESI-MS to the analysis of classes of compounds with a low molecular weight, such as basic drugs and their metabolites, antibiotics, steroids, oestrogens, benzodiazepines, pesticides, surfactants, and most other organic compounds amenable to El. LC-APCI-MS has been used to analyse PET extracts obtained by a disso-lution/precipitation procedure [147]. Other applications of hyphenated APCI mass spectrometric techniques are described elsewhere LC-APCI-MS (Section 7.33.2) and packed column SFC-APCI-MS (Section 73.2.2) for polar nonvolatile organics. 

The first example demonstrates the steps involved in working out the conditions for the separation of some steroids. Fig. 4.2a shows the structure of some conjugated oestrogens. 

Johnson AC, Belfroid A, Di Corcia A (2000) Estimating steroid oestrogen inputs into activated sludge treatment works and observations on their removal from the effluent. Sci Total Environ 256 163-173... 

The androgens and oestrogens represent the major male and female sex hormones respectively (Figure 11.B3). The testicular Leydig cells represent the primary source of androgens in the male, of which testosterone is the major one. Testosterone, in turn, serves as a precursor for two additional steroids, i.e. dihydrotestosterone and the oestrogen called oestradiol. These mediate many of its biological effects. 

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. 

Robertson JA, Bhattacharyya S, Ing NH (1998) Tamoxifen up-regulates oestrogen receptor-alpha, c-fos and glyceraldehyde 3-phosphate-dehydrogenase mRNAs in ovine endometrium. J Steroid Biochem Mol Biol 67(4) 285-292... 

Drugs that can be used to control tumour cell proliferation inhibit a variety of enzymes, including thymidylate synthase and topoisomerase (Chapter 20). The enzyme aromatase converts a ring in a steroid to an aromatic ring. It converts, for example, adrenal steroid hormones into female sex hormones, which bind to oestrogenic receptors in the ovary or breast and increase the risk of ovarian or breast cancer. Aromatase inhibitors are used to treat patients with breast or ovarian cancers that are sensitive to oestrogen. Unfortunately, none of the inhibitors is specific for enzymes in tumour cells and they can therefore have severe side-effects (Chapter 21). 

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

The follicular phase covers the development of the follicle, which involves an increase in its size due to an increase in follicular fluid, growth of the ovum (i.e. an increase in the contents of RNA and protein) and an increase in the number of cells that surround the ovum. These cells are of two types, the granulosa and the thecal cells. The role of these cells is to synthesise and secrete the steroid hormones oestrogens (mainly oestradiol). The precursor molecule for their synthesis is cholesterol. There is a division of labour between these cells the thecal cells convert cholesterol into the male sex hormones androstenedione and testosterone, which are released into the blood to be taken up by the granulosa cells where they are converted to the oestrogens (Figure 19.8). For details of pathways, see Appendix 19.1. 

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