Oestrogens biosynthesis

Fig. 12. Classical pathways for oestrogen biosynthesis, indicating 19-hydroxylation and 19-oxidation of 4-androstenedione and testosterone, followed by C-10.19 bond cleavage catalysed by a presumed C-10.19-lyase.

Fig. 13. Proposed mechanism for oestrogen biosynthesis involving double hydroxylation at C-19 and hy-droxylation at C-2 (see Ref. 52).

Fig. 14. Alternative mechanisms proposed for the C-10-C-19 bond cleavage step in oestrogen biosynthesis, involving hydroxylated intermediates (upper) and an enzyme-bound peroxide intermediate (lower). In the latter the arrows in structure XIV denote path b (from Ref. 104, with permission).

Fig. 15. Suggested dual role of a cyt P-450 - peroxide species (10) in the hydroxylation and C-10.19 bond cleavage steps in oestrogen biosynthesis (from Ref. 105, with permission).

An example of gene expression can be illustrated by consideration of the action of steroid hormones, and in the control of sterol biosynthesis. Steroid hormones enter the cell by diffusion through the plasma membrane and bind to their steroid hormone receptor. These receptors are part of a large related family that includes those for glucocorticoids, oestrogens, androgens, thyroid hormone, calcitriol and the retinoids. All steroid hormone receptors are zinc finger transcription factors. The receptor must ... 

The application of the twin ion technique [257] is also of importance in metabolism studies. The doubly labelled steroids [4- C+ 7-l- Ho.44]-androstenedione and [4- C + 7/3- Ho.42]-testosterone, were incubated with human placental microsomes and the resulting metabolites quantitated by counting C and identified by GC-MS [258]. The identified metabolites 17/8,19-dihydroxyandrost-4-en-3-one, 19-hydroxyandrost-4-en-3,17-dione, 17/8-hydroxy-3-oxo-androst-4-en-3-one, 3,17-dioxoandrost-4-en-19-al, oestradiol-17/3 and oestrone were easily recognisable from the double sets of relevant ions in their spectra due to the mixture of hydrogen and deuterium substitution at C-7. Hence the presence of the aromatizing enzymes in the placental preparation and the intermediates in oestrogen biosynthesis were confirmed. 

Oestrogen biosynthesis from androst-4-ene-3,17-dione involves preferential loss of 1/ - and 2j -hydrogen atoms, demonstrated by use of deuterium-labelled samples. ... 

The accepted pathway for the biosynthesis of the oestrogens from the appropriate androgen substrate is shown in Scheme 2.1. The conversion of either testosterone (16) or androstenedione (17) to their respective oestrogens, oestradiol and oestrone, is catalysed by a E-450-NADPH-flavoprotein-reduc-tase-dependent enzyme complex, aromatase (AR) [143, 144]. The overall... 

Covey, D.F. (1988), Aromatase inhibitors Specific inhibitors of oestrogen biosynthesis. In Berg and Plempel (eds). Sterol Biosynthesis Inhibitors. Ellis Horwood Ltd., Cambridge, pp. 534-571. 

Sulphated glycoproteins (mol. wts. >2.4 x 10 ) are biosynthesized, at least in the uterine luminal epithelial cells of the rat, under the stimulation of oestrogen but not progesterone, which inhibits their biosynthesis. ... 

Akhtar M, Corina D, Pratt J, Smith T (1976) Studies on the removal of C-19 in oestrogen biosynthesis using J Chem Soe Chem Commun 854-856... 

Akhtar M, Calder MR, Corina DL, Wright JN (1982) Mechanistic studies on C-19 demethylation in oestrogen biosynthesis. Biochem J 201 569-580... 

Hormonal effects on the biosynthesis of sulphated glycoprotein in the endometrium of rabbit uterus have been shown to be confined to the microsomal level. Oestrogen increases the incorporation of L-fucose and 2-acetamido-2-deoxy-D-glucose from their respective nucleotides into a microsomal fraction, while progesterone suppresses the incorporation of the two sugars. 

Parizek J (1964) Vascular changes at sites of oestrogen biosynthesis produced by parenteral injection of cadmium salts the destruction of placenta by cadmium salts. J Reprod Fertil 7 263-265... 

Further studies have been carried out on the role of oestrogen-like compounds in plants. The hypothesis that ergosterol peroxide is an artifact arising by attack of singlet oxygen on ergosterol has been further substantiated. A few aspects of the biosynthesis of the cucurbitanes, a class of oxygenated tetracyclic triterpenes, have been reviewed. ... 

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