Disease relevance of estradiol benzoate

• Treatment with low doses of estrogen (2 or 8 micrograms of estradiol benzoate (EB) 48 hr before sacrifice) was slightly but not significantly more effective in elevating hypothalamic progestin receptor content in age-matched females than in males despite the 40% greater body weights of males [1].
• When an additional dose of P was given up to 24 h prior to or 24 h after the EB, EB-P facilitation of lordosis was inhibited [2].
• While these data show that EB treatment does reduce the severity of some metabolic disturbances in a genetic model of type II diabetes, long-term estrogens do not appear to offer substantial advantages in the treatment of obesity or diabetes when compared with the effects of caloric restriction alone [3].
• Whereas precocious puberty resulted from the implantation of EB into the MPOA, a delay of puberty onset was induced by medial preoptic implants of the antiestrogen clomiphene citrate which also enhanced the LH-suppressing effect of s.c. administered EB in prepubertal females [4].
• In two subsequent experiments, nine of 26 cows were induced to have follicular cysts by follicular aspiration followed by 5 mg of EB [5].

Psychiatry related information on estradiol benzoate

• Ovariectomized rats fed the HF diet and given both EB and haloperidol exhibited significantly greater tumor number per rat, increased average tumor size, and reduced tumor latency period when compared to similarly treated rats fed the CF diet [6].
• Measures of EMG activity, response latency, and spike count were altered in castrates, but maintained in EB-treated castrates to the levels of intact males [7].
• In contrast, maternal behavior latencies were reduced by E/P/EB only among Sham-HYPX females [8].
• Gonadectomized male rats were submitted to REM sleep deprivation (REMd) for 120 hr and their hetero and homotypical sexual response to estradiol benzoate (EB) was tested [9].
• Feeding behavior was continuously monitored with photodetectors and recorded on an Esterline Angus event marker before and after a single SC injection of 6 micrograms of EB [10].

High impact information on estradiol benzoate

• A combined prenatal and neonatal regime of EB injections resulted in the abnormal presence of columnar epithelium in the vaginal fornices of some of the mice from each strain or stock [11].
• Sham-operated intact rats and bilaterally ovariectomized rats were given daily injections of haloperidol to increase prolactin secretion, bromocryptine to decrease prolactin secretion, and/or estradiol benzoate (EB) [6].
• Both EB and HAL significantly raised blood prolactin levels [12].
• Treatment for 8 days with EB produced a significant increase in mammary tumor incidence despite underfeeding, whereas underfed rats given the combination of HAL EB, and GH showed development and growth of mammary tumors equal to that of full-fed controls [12].
• In vitro one-point binding analyses of estradiol benzoate (EB)-induced cellular PRs and immunohistochemistry of PR in the mediobasal hypothalamus demonstrated a reduction in binding in the homozygous females, equivalent to background levels seen in EB-unresponsive tissue [13].

Chemical compound and disease context of estradiol benzoate

• Ovariectomized hamsters were administered estradiol benzoate (EB) and 44 h later, progesterone (P.) Lordosis behavior was induced [2].
• In Experiment 2, we tested the maternal behavior and measured estrogen receptor concentrations in OVX, steroid-primed, nulliparous rats after hysterectomy (H) and EB treatment [14].
• Conversely, PHEN infused into the MPOA of EB + P primed females transiently increased the number of seconds females held lordosis from 15 min to 2.0 h after infusion (maximum difference 64%; p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)[15]
• A dose of cordycepin that decreased lordosis when infused 1 h before injection of 0.5 microgram EB did not affect the behavior when infused 1 h before injection of 500 micrograms P [16].
• Conversely, HPA, which elevates endogenous GABA levels, was effective in facilitating lordosis behavior in sham-operated rats treated with EB only [17].

Biological context of estradiol benzoate

• Protein binding was eliminated by E2Bz [18].
• These data support the hypothesis that neonatal EB treatment may directly inhibit the synthesis or replenishment of the 8S estradiol "receptor" prior to the development of the persistent estrus syndrome (persistent vaginal estrus, anovulation and polycystic ovaries) [19].
• Injection of estradiol benzoate (EB, 5 mug/rat) 2 hr prior to, together with or following P treatment at 0300 hr of proestrus restored ovulation and the surge of LH [20].
• The ability of exogenous P to advance and amplify the LH surge on proestrus and in EB-primed ovariectomized rats appears to result in part from a reduction in the EOP inhibitory influence on LH secretion and may indicate a role for EOP in mediating the stimulatory effects of endogenous steroids on LH secretion in the female rat [21].
• However, blockade of ovulation was not reversed if EB was administered at 0500 or 0800 hr of proestrus following P treatment on diestrus II [20].

Anatomical context of estradiol benzoate

• One day after EB treatment, rats were bilaterally cannulated in the anterior ventromedial preoptic area (POA) [22].
• In a futher experiment in rats ovariectomized at 9 days of age, those treated neonatally with EB had significantly smaller uteri than their untreated ovariectomized controls, thus providing indirect evidence for an extravarian factor affected by neonatal treatment [19].
• These results demonstrate that the activation of cAMP phosphodiesterase after an injection of EB and the subsequent decrease in oviduct cAMP concentration are necessary for the epithelial cells to achieve their proliferative cycle [23].
• There was no significant effect of sex or EB treatment on ER mRNA levels in medial amygdala [24].
• Ovariectomized (OVX) ewes (n = 4/group) were given either 50 micrograms of estradiol benzoate (EB) or oil and were killed 16 h later for collection of the pituitary glands for immunohistochemistry and confocal microscopy [25].

Associations of estradiol benzoate with other chemical compounds

• In a second set of studies in EB plus P-treated rats, baclofen and muscimol decreased the steady state concentrations of norepinephrine in the medial preoptic area and medial basal hypothalamus for several hours and markedly decreased the turnover rate of norepinephrine in these areas [26].
• Steroid administration was patterned to approximate the plasma concentrations of endogenous ovarian steroids observed during 1) the follicular phase (EB), 2) luteal phase (EB+P), and 3) early pregnancy (EB+P+EB) [27].
• No PRL response could be detected in sham-operated, melatonin-treated animals after EB administration [28].
• When administered with EB, tamoxifen drastically increased oviduct cAMP concentration while it completely inhibited oviduct growth and the activation of cAMP phosphodiesterase induced by EB alone [23].
• However, when ovariectomy was delayed to allow normal E2 priming through diestrus II, administration of EB shortly after ovariectomy at 2300 hr of diestrus II elicited the normal proestrus surge of LH [20].

Gene context of estradiol benzoate

• In addition, while DPN lacked an agonistic action on peripheral tissue and serum pituitary reproductive hormones concentration, EB, PPT and PPT+DPN induced similar uterine ballooning and vaginal cornification, and increased and decreased, respectively, serum concentrations of PRL and gonadotropins [29].
• To this end, 2-week-old ovariectomized (OVX) rats were injected over 3 days with 25 microg estradiol benzoate (EB), 1.5 mg of propylpyrazole triol (PPT), a selective ERalpha agonist, 1.5 mg of the selective ERbeta agonist diarylpropionitrile (DPN) or a combination of PPT and DPN [29].
• EB, PPT and PPT+DPN treatments increased PR mRNA and the number and intensity of nuclei immunoreactive (IR) for PR in gonadotropes, and reduced the number of gonadectomy cells [29].
• Progesterone and NET significantly increased GnRH concentrations and reversed the EB-induced changes [30].
• Normal parthenogens did not increase ER mRNA in response to EB in either age group, in contrast to the strong response of 1-day-old males and females of the sexual species and 30-day-old created males [31].

Analytical, diagnostic and therapeutic context of estradiol benzoate

• Five days after ovariectomy, rats received oil or EB (30 micrograms/rat) at 1000 h on day 0 [32].
• Isotopic in situ hybridization histochemistry revealed that within the limbic-hypothalamic nuclei, levels of CCK and preproenkephalin (PPE) mRNA levels were significantly higher in EB and EB + T4-treated animals compared with T4 or oil-treated animals [33].
• In postnatal Week 16, subjects were gonadectomized, and blood samples were collected after treatment with 10 micrograms estradiol benzoate (EB), used to elicit an LH surge; subjects were subsequently treated with GnRH to test pituitary responsiveness [34].
• No treatment, EB only, and EB plus P served as control groups [35].
• In a separate group of acyclic, tumor-bearing females 42--56 days after transplantation, a single s.c. injection of 20 micrograms estradiol benzoate (EB) at 1030 h elicited significant increases in both serum LH and FSH values between 1700 and 1830 h on the next day [36].

References