Acta Reprod Turc. 1980 Jan;1(3):85-91.
Effect of oral contraceptive (ethinyl estradiol and d-norgestrel) on serum prolactin-oestradiol and progesterone levels.

Erodogan M, Inal A, Ozgu M, Beksac MS, Ergurbuz I.

PIP: The effect of oral contraceptives on serum concentrations of prolactin and the main ovarian steroids (estradiol and progesterone) was determined. Sera were assessed by radioimmunoassay. Mean concentrations of serum prolactin were 5.57, 10.28, and 10.28 ng/ml at onset (Day 5), middle (Day 14), and end (Day 28) of OC ingestion, respectively. During OC ingestion, prolactin concentration increment was significant (P .001). Raised levels of prolactin persisted until the end of the cycle. In the control group, mean prolactin levels were 5.68, 6.58, 8.79, 7.57, and 6.13 ng/ml on Days 1, 7, 14, 21, and 28 of the menstrual cycle, respectively. Serum estradiol levels were 80.48, 57.17, and 43.05 pg/ml on Days 5, 14, and 28 of oral contraception. Progesterone values were .29, .33, and .45, respectively. When estradiol and progesterone values of normal menstrual cycles (controls) were compared with the OC cycle, the decrease in estradiol was significantly lower and remained so without showing the cyclic pattern of normal menstruation. Serum progesterone levels were similarly affected.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12262090&dopt=Abstract estradiol




Brain Res. 2002 Oct 4;951(2):177-82.
17Beta-estradiol blocks NMDA-induced increases in regional cerebral O(2) consumption.

Weiss HR, Doshi D, Sinha AK, Liu X, Chi OZ.

Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics and Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.

We tested the hypothesis that 17beta-estradiol would reduce the cerebral O(2) consumption response to stimulation of N-methyl-D-aspartate (NMDA) receptors. We determined NMDA receptor density in 10 ovariectomized Wistar female rats equally divided into a control group and 17beta-estradiol (500 microg/21 days) treated group. An autoradiographic assay using 125I-MK-801, an NMDA antagonist, was used to measure specific binding to NMDA receptors. Another 14 ovariectomized rats were separated into 17beta-estradiol and control groups to determine cerebral blood flow (14C-iodoantipyrine) and O(2) consumption (microspectrophotometry). 17Beta-estradiol caused a 20% decrease in specific binding to cortical NMDA receptors. After topical cortical stimulation with 10(-3)M and 10(-4)M NMDA, blood flow increased significantly in control from 73+/-5 in the saline treated cortex to 110+/-8 ml/min/100 g with 10(-3)M NMDA. In contrast, there was no significant change in blood flow in the 17beta-estradiol treated animals. Cerebral O(2) extraction increased significantly in the 10(-3)M NMDA treated cortex in both groups. Cerebral O(2) consumption in the control group significantly increased by 53%, from 3.7+/-0.2 to 5.7+/-0.5 with 10(-4)M NMDA and 72% to 6.4+/-2.4 ml O(2)/min/100 g with 10(-3)M NMDA. The 17beta-estradiol group demonstrated no significant difference between the saline treated and NMDA treated cortex. Thus, 17beta-estradiol blocked the effects of NMDA on cerebral O(2) consumption and this was associated with a slightly decreased number of NMDA receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12270495&dopt=Abstract estradiol




Proc Am Assoc Cancer Res. 1956 Apr;2(2):146.
Reproducibility of method and hormonal influences in induction of breast cancer in rats by gastric instillation of methylcholanthrene [abstract]

Shay H, Gruenstein M, Harris C.

We have reported a high incidence and sex linkage of breast cancer in Wistar rats following gastric instillation of methylcholanthrene (J. Nat. Cancer Inst., 10:255, 1949, and 13:307, 1952). For this report, reproducibility of method and effects of estradiol and testosterone are evaluated in 103 male and 169 female rats which received methylcholanthrene 6 times a week throughout the experiments. The 169 female rats represent a pool of groups of 10 or more animals used as controls for experiments run during the past several years. Tumor incidence ranged from 73-100%, with a combined average of incidence 82%. The high incidence of pituitary tumors in both sexes treated with estradiol; the decrease in breast cancers in methylcholanthrene-treated females receiving testosterone or estradiol; and the incidence of breast cancers in both sexes receiving only estradiol permit speculation regarding the role of the pituitary gland in induction of breast cancer by methylcholanthrene in our experiments. The sharp drop in incidence of breast tumor in animals receiving methylcholanthrene and estradiol suggests involvement of a pituitary factor or factors in induction of breast tumors by methylcholanthrene; with the development of pituitary tumors in animals receiving estradiol, these factors may no longer be available. Estradiol-induced breast cancer in the rat may utilize a mechanism independent of the pituitary. full text

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Neuropharmacology. 2003 Apr;44(5):584-91.
Uncoupling of 5-HT1A receptors in the brain by estrogens: regional variations in antagonism by ICI 182,780.

Mize AL, Young LJ, Alper RH.

Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas School of Medicine, Kansas City, USA.

Previously we have shown that 17beta-estradiol (in vivo and in vitro) rapidly decreases the function of serotonin(1A) (5-HT(1A)) receptors, allowing us to hypothesize that 17beta-estradiol accomplished this via activation of a membrane estrogen receptor. Hippocampus and frontal cortex obtained from ovariectomized rats were incubated with 17beta-estradiol or bovine serum albumin (BSA)-estradiol in the presence or absence of the estrogen receptor (ER) antagonist ICI 182,780. Membranes were prepared to measure R(+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding (a measure of 5-HT(1A) receptor coupling and function). In both hippocampus and frontal cortex, 17beta-estradiol and BSA-estradiol (50 nM) decreased R(+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding. ICI 182,780 blocked the effect of both the estrogens in hippocampus, but only the effect of 17beta-estradiol in frontal cortex. Due to the inability of ICI 182,780 to block the effects of BSA-estradiol in frontal cortex, similar experiments were performed using the selective estrogen receptor modulator tamoxifen as the agonist. Tamoxifen (100 nM and 1 microM) decreased R(+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding. ICI 182,780 (1 microM) blocked the ability of tamoxifen to decrease 5-HT(1A) receptor coupling in the hippocampus, but not in the frontal cortex. Taken together, these data support the existence of a pharmacologically distinct ER in hippocampus vs. frontal cortex that might be responsible for rapid uncoupling of 5-HT(1A) receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12668044&dopt=Abstract estradiol




J Obstet Gynaecol. 1994;4 Suppl 1:S1-34.
A review of "once-a-month" combined injectable contraceptives.

Newton JR, D'arcangues C, Hall PE.

PIP: The once-a-month combined progestogen and estrogen injectables were developed to overcome menstrual irregularity, a major reason for discontinuation of progestogen-only contraceptives. About 2 million women have already used the combined once-a-month injectables, particularly in Latin America and China. The currently available once-a-month combined injectable contraceptives are Chinese Injectable No. 1 (17 alpha-hydroxyprogesterone caproate, estradiol valerate), another formulation marketed under various brand names in Latin America (dihydroxyprogesterone acetophenide, estradiol enanthate), Cyclofem (medroxyprogesterone acetate [MPA], estradiol cypionate), Mesigyna (norethisterone enanthate, estradiol valerate), and Mego-E (megestrol acetate, 17 beta-estradiol). Cyclofem and Mesigyna are very effective at preventing pregnancy (1-year rate, 99.8-99.6%). The rate for the dihydroxyprogesterone acetophenide/estradiol enanthate formulation is 100%, while that for Chinese Injectable No. 1 is 94%. Even though menstrual disturbances occur less often in once-a-month injectable users, they are the leading medical reason for discontinuation. At 1 year of use, about 70% of Cyclofem and Mesigyna users have regular bleeding patterns compared to 8% of Depo-Provera users. None of the Cyclofem and Mesigyna studies have found them to induce any adverse or clinically relevant metabolic changes. Once-a-month combined estrogen and progestogen injectables do not cause any significant delay in return to ovulation, but researchers should collect more data on conception rates for women who discontinue for planned pregnancy and those who discontinue for bleeding disorders and amenorrhea. Research into service delivery of these injectables is needed to assess managerial requirements or adaptations that would be required should there be more wide scale introduction of a cont




Cytokine. 2003 Jan 21;21(2):91-7.
Mechanism of the salutary effects of 17beta-estradiol following trauma-hemorrhage: direct downregulation of Kupffer cell proinflammatory cytokine production.

Yokoyama Y, Kuebler JF, Matsutani T, Schwacha MG, Bland KI, Chaudry IH.

Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Kupffer cells have been reported as a major source of proinflammatory cytokines (i.e. IL-6, TNF-alpha), which have been implicated in the pathogenesis of trauma-hemorrhage. Previous studies have shown a protective effect of 17beta-estradiol on immune function and physiological responses following trauma-hemorrhage. In this study, we investigated whether 17beta-estradiol has a direct effect on Kupffer cell cytokine production following trauma-hemorrhage. Male Sprague-Dawley rats were subjected to trauma (midline laparotomy) and hemorrhage (35-40 mmHg for 90 min followed by fluid resuscitation) or sham operation. Two hours later, Kupffer cells were isolated and cultured with 17beta-estradiol in the presence and absence of lipopolysaccharide stimulation. Kupffer cell IL-6 and TNF-alpha production increased following trauma-hemorrhage. Incubation with 17beta-estradiol attenuated the production of IL-6 by cells from both sham and trauma-hemorrhage animals in a dose-dependent manner. The suppression of IL-6 production by 17beta-estradiol was paralleled by a decrease in mRNA levels. In contrast to IL-6, the effects of 17beta-estradiol on TNF-alpha production were minimal. In conclusion, these results indicate the direct downregulation of Kupffer cell IL-6 production by 17beta-estradiol at a molecular level, which might explain in part the previously observed salutary effects of estradiol treatment following trauma-hemorrhage.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12670448&dopt=Abstract estradiol




Contracept Fertil Sex (Paris). 1981 Oct;9(10):623-9.
[What happens in our patients' bodies to the steroid hormones we prescribe? Pt. 1. Estrogens]

[Article in French]

Rozenbaum H.

PIP: The variations observed in the plasmatic half-life of estrogens vary greatly depending on several factors such as dosage, mode of administration, and the patient. Such variations have not been completely explained. Ethinyl estradiol is not converted into estrone; it is quickly absorbed and its maximum plasmatic level is reached in 1-2 hours. The duration of ethinyl estradiol's plasmatic half-life is 1-7 hours for the diffusion phase, and 6-48 hours for the elimination phase. These variations depend on the different methods of dosage and on individual variations among patients. Conjugated equine estrogens at a dose of 1.25 mg/day double the initial estradiol plasmatic level and increase 4 times that of estrone. Natural estrogens, especially estradiol, administered per os are quickly converted by the intestinal wall into estrone and estrone sulphate. In the vaginal route of administration, estradiol, estrone, and estriol quickly pass through the cervical mucus and into the plasma. The nasal and sublingual modes of administration rapidly convert estradiol into estrone, while the absorption rate through the cutaneous mode is even quicker, and subcutaneous implantation guarantees constant plasmatic levels for about 6 months. All different routes of administration have advantages and disadvantages; it is often advisable, when possible, to let the patient choose a preferred mode of administration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12311060&dopt=Abstract estradiol




Pain. 2003 Apr;102(3):227-34.
Stress-induced visceral hypersensitivity in female rats is estrogen-dependent and involves tachykinin NK1 receptors.

Bradesi S, Eutamene H, Garcia-Villar R, Fioramonti J, Bueno L.

Institut National de la Recherche Agronomique, Neuro-Gastroenterology and Nutrition Unit, 180 chemin de Tournefeuille, B.P. 3, 31931 Toulouse, France.

Hormonal cycling may be related to a higher incidence of pain syndrome in female. As tachykinins are pivotal in stress-induced colonic dysfunction, we investigated whether ovarian steroids influence stress-induced visceral hypersensitivity to rectal distension (RD) in female rats and further, whether this influence involves NK1 receptors. Female Wistar rats, either intact or ovariectomized (OVX), were equipped for abdominal muscle electromyography and submitted to 2-h partial restraint stress (PRS) or sham-PRS. First, the effect of PRS was evaluated in intact rats. Second, abdominal response to RD was recorded in OVX rats treated with either, progesterone, 17beta-estradiol, 17beta-estradiol-plus-progesterone, or vehicle, in both basal and PRS conditions. Third, the NK1 receptor-antagonist, SR140333, was tested in PRS-intact and PRS-OVX rats under 17beta-estradiol or 17beta-estradiol-plus-progesterone treatment. PRS induced visceral hypersensitivity to RD and this effect was prevented by ovariectomy. OVX rats treated with 17beta-estradiol or 17beta-estradiol-plus-progesterone, but not progesterone alone, exhibited visceral hypersensitivity after PRS similar to that of intact rats. Both stress-induced visceral hypersensitivity in intact rats and the hormonally-restored visceral hyper-responsiveness of OVX rats were antagonized by SR140333. It is concluded, therefore, that stress-induced visceral hypersensitivity in female rats is estrogens-dependent and mediated through NK1 receptor activation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12670663&dopt=Abstract estradiol




Brain Res Mol Brain Res. 2003 Apr 10;112(1-2):170-6.
Estrogen receptor alpha forms estrogen-dependent multimolecular complexes with insulin-like growth factor receptor and phosphatidylinositol 3-kinase in the adult rat brain.

Mendez P, Azcoitia I, Garcia-Segura LM.

Instituto Cajal, C.S.I.C., Av. Dr. Arce 37, 28002, Madrid, Spain.

Estradiol and insulin-like growth factor-I (IGF-I) have numerous functional interactions in the brain, including the regulation of neuroendocrine events, the control of reproductive behavior and the promotion of synaptic plasticity and neuronal survival. To explore the mechanisms involved in these interdependent actions of estradiol and IGF-I in the adult brain, the potential interactions of estrogen receptors with components of the IGF-I signaling system were assessed in this study. Systemic estradiol administration resulted in a transient immunocoprecipitation of the IGF-I receptor with the estrogen receptor alpha and in a transient increase in tyrosine phosphorylation of the IGF-I receptor in the hypothalamus of adult ovariectomized Wistar rats. Both effects were coincident in time, with a peak between 1 and 3 h after systemic estradiol administration. Three hours after estradiol treatment, there was an enhanced immunocoprecipitation of estrogen receptor alpha with p85 subunit of phosphatidylinositol 3-kinase, as well as an enhanced immunocoprecipitation of p85 with insulin receptor substrate-1. The interaction with the IGF-I receptor was specific for the alpha form of the estrogen receptor and was also induced by intracerebroventricular injection of IGF-I. These hormonal actions may be part of the mechanism by which estradiol activates IGF-I receptor signaling pathways in the brain and may explain the interdependence of estrogen receptors and the IGF-I receptor in synaptic plasticity, neuroprotection and other neural events.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12670715&dopt=Abstract estradiol