Estrogenic and Antiestrogenic Effects of Clomiphene, MER-25 and CN-55,945-27 on the Rat Uterus and Vagina

Wood, Joan R.; Wrenn, T.R.; Bitman, Joel

doi:10.1210/endo-82-1-69

Cited by 34 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…it has the lowest oestrogenic effect (no hyper trophy of the adrenals in males, no atrophy of the testes, the smallest decline in weight of the seminal vesicles). This is in keeping with data in the literature on the absence of oestrogenic activity of MER 25 [16], though according to some reports, some oestrogenic activity is present also in this substance [1,17]. MER 25 alone was the only one of the tested anti-oestrogens which caused a decrease of thyroxine binding to adenohypophysial proteins in males in vitro, as far as inhibition of the adenohypophysial response to oestradiol is concerned-clomiphene had the greatest anti-oestrogenic effect -again only in males.…”

Section: Discussionsupporting

confidence: 92%

Comparison of the Effect of Three Anti-Oestrogens on the Reaction of the Rat Adenohypophysis to Oestrogen

Schreiber¹,

Pribýl²,

Rohácová³

1972

Horm Res Paediatr

View full text Add to dashboard Cite

Male and female rats were injected with oestradiol benzoate, 1 mg twice a week. In the diet they received 0.034%_o clomiphene citrate, SQ 10.591 and MER 25, the administration of the oestrogen being combined with the above-mentioned anti-oestrogens In male rats, 3 weeks administration of clomiphene did not cause a change, SQ 10.591 caused a slight increase and MER 25 a slight decrease in the weight of adenohypophysis. Clomiphene slightly reduced, SQ 10.591 did not affect, and MER 25 reduced considerably thyroxine binding to adenohypophysial proteins in vitro. Hypertrophy of the adenohypophysis after oestrogens was somewhat prevented by clomiphene and less by SQ 10.591 and MER 25. The increase of thyroxine binding to adenohypophysial proteins in vitro after oestrogen was influenced in a similar way. Clomiphene and SQ 10.591 increased the weight of the adrenals and reduced the weight of the testes. The weight of the seminal vesicles declined most after clomiphene, less after SQ 10.591 and least after MER 25. In female rats the weight of the adenohypophysis increased considerably after oestrogen, declined slightly after clomiphene and did not change after the other two anti-oestrogens. None of the administered anti-oestrogens prevented the increase in the weight of the adenohypophysis after oestrogen, and with the exception of MER 25, they did not prevent the increase of thyroxine binding to adenohypophysial proteins in vitro. Under the above experimental conditions (large dose of oestrogen), clomiphene seems to be the most effective anti-oestrogen and MER 25 the purest one, i.e. the anti-oestrogen most devoid of oestrogenic activity.

show abstract

Section: Discussionsupporting

confidence: 92%

Comparison of the Effect of Three Anti-Oestrogens on the Reaction of the Rat Adenohypophysis to Oestrogen

Schreiber¹,

Pribýl²,

Rohácová³

1972

Horm Res Paediatr

View full text Add to dashboard Cite

show abstract

“…Clomiphene has since been shown to decrease plasma testosterone in prepubertal boys (19) and to suppress plasma gonadotropins in adult males with "hypogonadotropic eunuchoidism" (20). The unexpected finding of gonadotropin 'suppression in contrast to the stimulatory response elicited in adults given clomiphene citrate (21)(22)(23)(24), was attributed to the intrinsic estrogenic properties of clomiphene citrate (25). The current results with ethinyl estradiol, a potent semisynthetic estrogen, support this interpretation.…”

Section: Discussionsupporting

confidence: 54%

Suppression of Urinary and Plasma Follicle-Stimulating Hormone by Exogenous Estrogens in Prepubertal and Pubertal Children

Kelch¹,

Kaplan²,

Grumbach³

1973

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Clomiphene citrate, an "anti-estrogen" with mild estrogenic properties, inhibits rather than stimulates gonadotropin excretion in prepubertal and early pubertal children. These and other data suggest that the sensitivity of the hypothalamic-pituitary "gonadostat" decreases at the onset of puberty. To test this hypothesis further, the daily excretion of urinary folliclestimulating hormone (FSH) and luteinizing hormone (LH) was determined in 19 children (5 "short normals" and 14 with isolated human growth hormone (HGH) deficiency) who were given ethinyl estradiol (EE) 1.4-14.7 Ag/m2 per day (2-10 Ag/day) for 4 to 7 days. In addition, plasma and urinary gonadotropins and plasma estrogens were serially determined in two prepubertal females( with isolated HGH deficiency) given two injections (24 h apart) of estradiol benzoate, 10 isg/kg.FSH and LH concentrations in plasma and kaolin-acetone urinary concentrates and plasma 173-estradiol (E2) and estrone (El) were measured by radioimmunoassays. 2-3 Ag/m2 per day of EE significantly suppressed urinary FSH (and LH when detected in the control period) in two out of six prepubertal children, while all doses > 5 ,ug/m2 per day suppressed urinary gonadotropins to undetectable levels in eight prepubertal subjects. In early to midpubertal subjects, 2-10 Ag/m2 per day of EE produced a slight suppression of urinary FSH, but failed to suppress to undetectable levels. gonadotropins remained suppressed for the duration of the study (3 days). Plasma E2 and Ei rose from prepubertal values to peak concentrations of 150 to 250 pg/ml (E2), and 50 and 100 pg/ml (Ei) at approximately 36 h. We conclude that the hypothalamic-pituitary-gonadal axis is operative in the prepubertal child and that the sensitivity of the hypothalamic-pituitary center(s) which control the secretion of FSH and LH decreases at the onset of puberty in man. INTRODUCTIONMounting evidence suggests that the gonads in the prepubertal human being are not quiescent and, in fact, play a significant role in regulating the release of gonadotropins (1-4). Previous reports from this laboratory (5, 6) demonstrated that clomiphene citrate, an "anti-estrogen" with mild estrogenic properties, suppresses the excretion of urinary follicle-stimulating hormone (FSH) in prepubertal children. As little as 1 mg/m2 per day of oral clomiphene citrate decreases

show abstract

“…Both are partial estrogen agonists and mediate initial estrogenic responses in the uterus and vagina. When administered with estradiol these drugs exhibit potent antiestrogenic effects (5). Both trans-tamoxifen and trans-4-hydroxytamoxifen have antitumor activity in estrogen-dependent cancers (6).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the Estrogen Receptor Interaction with 4-Hydroxytamoxifen

Sasson

Notides

1988

Molecular Endocrinology

View full text Add to dashboard Cite

The binding mechanism of the estrogen receptor with 4-[3H]hydroxytamoxifen was investigated. The equilibrium binding analysis with 4-[3H]hydroxytamoxifen indicated a positive cooperative interaction: the Scatchard plot was convex and the Hill coefficient was 1.4-1.5. This binding appears similar to the positively cooperative interaction of the estrogen receptor with [3H]estradiol. However, a competitive binding assay with a saturating concentration of [3H] estradiol and variable concentrations of 4-hydroxytamoxifen produced nonparallel displacement curves indicating that the binding mechanism of the receptor with these two ligands is different. The competitive binding assay with [3H]estradiol and 4-hydroxytamoxifen at constant molar ratios demonstrated that the receptor's affinity for estradiol was reduced and the receptor preferentially bound 4-hydroxytamoxifen. These data suggest that 4-hydroxytamoxifen interacts with the receptor differently than estradiol; it antagonizes the binding of estradiol when these two ligands are simultaneously present.

show abstract

Estrogenic and Antiestrogenic Effects of Clomiphene, MER-25 and CN-55,945-27 on the Rat Uterus and Vagina

Cited by 34 publications

References 0 publications

Comparison of the Effect of Three Anti-Oestrogens on the Reaction of the Rat Adenohypophysis to Oestrogen

Comparison of the Effect of Three Anti-Oestrogens on the Reaction of the Rat Adenohypophysis to Oestrogen

Suppression of Urinary and Plasma Follicle-Stimulating Hormone by Exogenous Estrogens in Prepubertal and Pubertal Children

Mechanism of the Estrogen Receptor Interaction with 4-Hydroxytamoxifen

Contact Info

Product

Resources

About