Estrogens and Antiestrogens

Geynet, Claudine; Millet, C.; Truong, H; Baulieu, Étienne-Émile

doi:10.1159/000301742

Cited by 59 publications

(20 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The inhibition of the oestradiol binding was competitive and cyclofenil bound to the oestrogen receptor with high affinity, Kd] = 0-94 IO-8 mol/1. The affinity of cyclofenil for the oestrogen receptor is of the same order as that reported by Geynet, Millet, Truong & Baulieu (1972) and is similar to the affinities for the oestrogen receptor determined for the oestrogen antagonists clomiphene and tamoxifen, but is lower than that determined for oestradiol and diethylstilboestrol (Geynet et al, 1972;Ginsburg et al, 1977;Wakeling & Slater, 1980). The in-vivo effects of cyclofenil upon the cytoplasmic oestrogen receptor concentrations were complicated and did not follow a simple dose-related depletion as has been observed for the non-steroidal oestrogen antagonists (Jordan, Dix, Naylor, Prestwich & Rowsby, 1978;Kurl & Morris, 1978;Katzenellenbogen et al, 1980).…”

Section: Discussionsupporting

confidence: 81%

Biological activity and steroid receptor interactions of cyclofenil with the oestrogen target tissues of the brain, pituitary gland and uterus of the rat

Sp¹,

Leake²,

Id³

1982

Reproduction

View full text Add to dashboard Cite

In vitro cyclofenil [bis-(p-acetoxyphenyl)-cyclo-hexylidene methane] competitively inhibited the binding of [3H]oestradiol-17\g=b\ to the uterine cytoplasmic receptor (Kdi = 9\m=.\41 nmol/l). By 24 h after cyclofenil treatment of ovariectomized rats, cytoplasmic oestrogen receptors were altered, in a similar manner, in brain, pituitary gland and uterus. The lowest dose depleted the receptor concentration which was re-established at the intermediate dose and depleted again after the highest dose. Nuclear oestrogen receptors measured in the uterus were raised only after the highest dose of cyclofenil. Uterine cytoplasmic progesterone receptors were increased after cyclofenil, the concentration of progesterone receptor after the high dose of cyclofenil being greater than after a large dose of oestradiol-17\g=b\ or oestradiol-17\g=b\ benzoate. Cyclofenil was uterotrophic; the increase in uterine weight was apparently dose-related and at 24 and 48 h the increase was greater or similar to the increases produced by oestradiol-17\g=b\ or oestradiol-17\g=b\ benzoate. Accumulation of uterine luminal fluid was also observed but oestradiol-17\g=b\ benzoate was more active in this respect. Cyclofenil antagonized all the uterine effects of oestradiol-17\g=b\ benzoate in the immature female rat but only the changes in uterine luminal fluid in the adult ovariectomized rat. Cyclofenil decreased serum LH and increased serum FSH concentrations, effects similar to those of oestrogen except when administered as three daily doses when, unlike oestrogen, no changes in FSH were observed. Antagonism of the activity of oestrogen upon the serum gonadotrophins was not seen. Serum prolactin concentrations were increased 24 h after 0\m=.\5 and 50 mg cyclofenil/kg but not after 10 mg/kg. Cyclofenil was not active in inducing sexual receptivity in ovariectomized adult rats unless previously treated with progesterone when a high level of activity was observed. The results show that the cyclofenil molecule possesses high oestrogenicity which is probably mediated via the oestrogen receptor system. This would suggest that the mechanism by which cyclofenil induces ovulation is most probably related to its oestrogenicity rather than its antioestrogenicity.

show abstract

Section: Discussionsupporting

confidence: 81%

Biological activity and steroid receptor interactions of cyclofenil with the oestrogen target tissues of the brain, pituitary gland and uterus of the rat

Sp¹,

Leake²,

Id³

1982

Reproduction

View full text Add to dashboard Cite

show abstract

“…On the other hand, 7α-methyl-estradiol has high affinity (K i = 0.1-1 nM) for the receptor [28]. Our results support the suggestion that shorter alkyl side chains will improve the in vivo targeting properties of C-7α-[ 18 F]FES derivatives.…”

Section: Discussionsupporting

confidence: 84%

Synthesis and evaluation of 7α-(3-[18F]fluoropropyl) estradiol

Okamoto

Naka

Kitagawa

et al. 2015

Nuclear Medicine and Biology

View full text Add to dashboard Cite

“…First the receptor-adsorbent complex dissociates slowly at 0 C. This dissociation rate may be increased by raising the elution temperature to 28-30°C [20,22] or by addition of chaotropic ions, such as NaSCN [23]. With adsorbent 111, both methods gave similar results and we routinely used the increase of temperature for elution of the receptor in the presence of an excess of free oestradiol.…”

Section: Parameters Influencing the Elution Of The Receptor Bound To mentioning

confidence: 99%

Properties of Biospecific Adsorbents, Obtained by Immobilization of Oestradiol 7α‐Derivatives, for Purification of Calf‐Uterine Cytosol Oestradiol Receptor

Redeuilh

Richard-Foy

Secco

et al. 1980

European Journal of Biochemistry

View full text Add to dashboard Cite

The properties of three types of adsorbents obtained by coupling oestradiol 7a-derivatives to agarose were compared. The adsorbents examined were : oestradiol 7x-decamethylene-agarose, oestradiol 7r.-decamethylene-poly(alanyl-lysine)-a~arose and oestradiol 7a-trimethylene-poly(alanyl1ysine)-agarose. The following results were obtained.(1) All these adsorbents are stable at 0 -C for at least a year when stored in water. In the presence of cytosol they are stable for several hours and are reusable after a simple wash. (2) A new method allowing the calculation of the maximal receptor binding capacity of an absorbent was developed. The use of these adsorbents for the purification of the trypsin-treated receptor directly from cytosol allowed a 2500-fold purification corresponding to 5 Y! pure protein (assuming one oestradiol binding site per molecule of M , 60000). When starting from a low salt preparation containing the native 8-S receptor, partially purified by heparin-Ultrogel chromatography, preliminary experiments using affinity chromatography gave a further purification of 250 -500-fold and led to a 50 -90 "( pure protein (assuming one oestradiol binding site per molecule of M , 70000).The use of affinity chromatography has been proposed as a necessary step for purification of hormone receptor. We have attempted to find an adsorbent convenient for the purification of oestradiol receptor from calf uterine cytosol. Two different forms of receptor may be characterized by their sedimentation coefficients: 8-S receptor [l] and 4-5-S receptor [2] in low and high salt concentration, respectively. This oestradiol receptor is difficult to purify because of its non-specific and irreversible aggregation with cytosol proteins. Mild trypsin treatment leads to a nonaggregatable form of the receptor [3] with a sedimentation coefficient of 4 S, whatever the ionic conditions [4]. For this reason the 4-S receptor was used for a systematic investigation of the parameters influencing purification by affinity chromatography. This 4-S Abbreviution. Poly(Ala-Lys), poly(oL-alanyl-L-lysine) copolymer. molecular form of the receptor is probably biologically inactive (unable to translocate to nucleus or to bind DNA), but its binding properties to the hormone remain unchanged.New biospecific adsorbents have been previously synthesized and studied in this laboratory [5]. The affinity of the receptor for the adsorbent was found to depend on the position at which the spacer is fixed onto the steroid, and therefore an oestradiol derivative carrying a long spacer chain i.e. decamethylene, ( C H Z )~~, attached at the 7a position was coupled to an insoluble matrix [5]. Such adsorbents offer many advantages in comparison with some previously described [6,7], in particular: (a) great stability due to the absence of ester bonds in the spacer chain, and (b) high degree of selectivity for the receptor since the 7a position of fixation of the spacer chain does not interfere with the high affinity of the receptor for the immobilized ligand.

show abstract

Estrogens and Antiestrogens

Cited by 59 publications

References 11 publications

Biological activity and steroid receptor interactions of cyclofenil with the oestrogen target tissues of the brain, pituitary gland and uterus of the rat

Biological activity and steroid receptor interactions of cyclofenil with the oestrogen target tissues of the brain, pituitary gland and uterus of the rat

Synthesis and evaluation of 7α-(3-[18F]fluoropropyl) estradiol

Properties of Biospecific Adsorbents, Obtained by Immobilization of Oestradiol 7α‐Derivatives, for Purification of Calf‐Uterine Cytosol Oestradiol Receptor

Contact Info

Product

Resources

About