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Chemical Compound Review

BSPBio_002004     [(13S,17S)-3-hydroxy-13- methyl-6,7,8,9,11...

Synonyms: KBioGR_001201, KBioSS_001532, CCG-40191, NINDS_000883, SPBio_001005, ...
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Disease relevance of estradiol valerate

  • The steroidal responses of the gland to beta-adrenergic receptor stimulation and hCG were examined in vitro 60 days after EV administration, i.e. at the time when follicular cysts are well established [1].
  • The ovaries from EV-treated animals were smaller than those of controls and the cystic follicles exhibited marked thecal hypertrophy and attenuation of the granulosa cell layer [2].
  • Uterine flushings and endometrium were collected from one uterine horn of cyclic gilts on Day 11; then, at 1, 6, 12, and 24 h following a single injection of estradiol valerate (EV; 5 mg, into adipose tissue), uterine flushings and endometrium were collected from the second uterine horn [3].
  • CONCLUSION: Thus, rats with EV-induced PCO develop hypertension and increased sympathetic and HPA-axis activity without reduced insulin sensitivity, obesity, or hyperandrogenism [4].

High impact information on estradiol valerate

  • The HRT-EVP group (n = 26) used sequential estradiol valerate (EV) plus progestin (levonorgestrel), the HRT-EV group used EV alone (n = 32), and the control group (n = 30) used no HRT [5].
  • The results demonstrate that an activation of the sympathetic neurons innervating the ovary precedes the development of cysts in EV-induced PCOS and raise the possibility that a derangement of sympathetic inputs to the ovary contributes to the etiology of PCOS [6].
  • RESULTS: An omnibus significance test revealed Climodien to increase activity in 882 of 2,394 voxels in the alpha-2 band, followed by 733, 706, and 664 voxels in the beta-2, beta-1, and beta-3 bands, and 509 voxels in the delta band, whereas 2 mg EV alone did not produce a significant suprathreshold activity [7].
  • Repeated EA treatments in EV-injected rats significantly increased beta-endorphin concentrations in the hypothalamus [8].
  • Otherwise, treatment with 80 mg OP for 1 mo, 20 mg OP for 1 or 2 mo, or 0.8 microg EV for 1 mo had little or no effect on the histology of the tissues we examined [9].

Biological context of estradiol valerate

  • The basal plasma LH concentration at 9 weeks after EV treatment were significantly lower than in proestrus controls and plasma concentrations of LH elicited by LHRH pulses was significantly lower than in controls [2].
  • In subjects with the GG genotype, the oxLDL-ab titer increased in the order of 2.13 in controls, 2.53 in the EV group and 3.21 in the EVP group (ANOVA for trend p = 0.006) [10].
  • Two experiments were conducted to evaluate the efficacy of a 3-mg ear implant of norgestomet, left in situ for 10 days, in conjunction with a single injection of 1.5 mg norgestomet and 0.5 mg estradiol valerate (EV) for controlling fertile estrus in the ewe [11].
  • The Menopause Rating Scale II (MRS II) was used to assess the effect of EV/LNG on the menopausal symptoms [12].
  • Intact MA hosts given EV when young were unable to support any estrous cycles when given young ovarian grafts, whereas MA hosts ovariectomized and given EV when young exhibited impairments similar to intact MA hosts not given EV [13].

Anatomical context of estradiol valerate

  • In spite of the diminished LH surge elicited in response to LHRH, the EV-treated animals ovulated as indicated by the presence of fresh corpora lutea on the ovaries [2].
  • We found that an 80-mg dosage of OP for 2 mo or an 8-microg dosage of EV for 1 or 2 mo greatly reduced sperm numbers and adversely influenced the sizes, weights, and histological structures of the testes, epididymides, ventral prostate glands, seminal vesicles, and coagulating glands [9].
  • Hence, EV exposure prior to 12 days of age (as short as 1-3 days postnatal), but not after 12 days of age, results in long-term abnormal penile morphology, characterized by abnormal accumulation of fat cells in the corpora cavernosa penis and, consequently, loss of fertility [14].
  • Two weeks following capsule insertion, EV decreased TH activity and DA concentration in the arcuate nucleus (AN) while no significant changes in TH activity or DA concentration were observed in the SNR, ventromedial nucleus (VMN), suprachiasmatic nucleus, paraventricular nucleus, medial preoptic nucleus, or the periventricular preoptic nucleus [15].
  • Our evidence strongly indicates that the role of the sympathetic nervous system is crucial in the pathogenesis of EV-induced PCO [16].

Associations of estradiol valerate with other chemical compounds


Gene context of estradiol valerate

  • An increase in the expression of ovarian TH after EV injection was also detected, suggesting a structural and functional remodelling of ovarian sympathetic innervation in PCO rats [16].
  • Endometrial PRL receptor numbers were higher (p less than 0.05) at both 1 h and 6 h after treatment with EV and then decreased (p less than 0.02) by 12 h to below pretreatment values [3].
  • Postmenopausal women were randomly given either oral calcium (500 mg/day, control group, n = 12) or a combination of estradiol valerate (EV, 2 mg/day for 21 days) with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the treatment cycle, n = 19) [18].
  • CONCLUSIONS: The effects of HRT on LDL oxidation can vary according to MPO genotype and the concurrent progestin therapy with EV may counteract the more neutral effect of EV on LDL oxidation in subjects with the MPO high-expression genotype [10].
  • Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action [19].

Analytical, diagnostic and therapeutic context of estradiol valerate

  • The difference in tumor burden attributed to dietary lipid seen in intact rats was less in ovariectomized rats and greater in ovariectomized rats treated with EV, despite the fact that absolute tumor burden was reduced by this treatment [20].
  • At the age of 15 weeks, ovariectomized (OVX) rats received intramuscular injection of estradiol valerate (EV) 5 microg (OVX+EV 5 microg group; n = 6), EV 25 microg (OVX+EV 25 microg group; n=7), or placebo (OVX group; n = 8), and sham-operated rats received placebo (sham group; n = 8) [21].
  • The percentage of ewes synchronized was not significantly affected by progestin treatment (Experiment 1-cronolone pessary alone, 96%; norgestomet implant and injection of norgestomet and EV, 92%; Experiment 2-cronolone pessary + injection of norgestomet and EV, 84%; Norgestomet implant + injection of norgestomet and EV, 96%) [11].


  1. Ovarian steroidal response to gonadotropins and beta-adrenergic stimulation is enhanced in polycystic ovary syndrome: role of sympathetic innervation. Barria, A., Leyton, V., Ojeda, S.R., Lara, H.E. Endocrinology (1993) [Pubmed]
  2. Pituitary and ovarian responses to luteinizing hormone releasing hormone in a rat with polycystic ovaries. Hemmings, R., Farookhi, R., Brawer, J.R. Biol. Reprod. (1983) [Pubmed]
  3. Effect of pregnancy and exogenous ovarian steroids on endometrial prolactin receptor ontogeny and uterine secretory response in pigs. Young, K.H., Kraeling, R.R., Bazer, F.W. Biol. Reprod. (1990) [Pubmed]
  4. Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity. Stener-Victorin, E., Ploj, K., Larsson, B.M., Holmäng, A. Reprod. Biol. Endocrinol. (2005) [Pubmed]
  5. Hepatic lipase C-480T genotype-dependent benefit from long-term hormone replacement therapy for atherosclerosis progression in postmenopausal women. Fan, Y.M., Dastidar, P., Jokela, H., Punnonen, R., Lehtimäki, T. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  6. Activation of ovarian sympathetic nerves in polycystic ovary syndrome. Lara, H.E., Ferruz, J.L., Luza, S., Bustamante, D.A., Borges, Y., Ojeda, S.R. Endocrinology (1993) [Pubmed]
  7. Identifying target regions for vigilance improvement under hormone replacement therapy in postmenopausal syndrome patients by means of electroencephalographic tomography (LORETA). Saletu, B., Anderer, P., Saletu-Zyhlarz, G.M., Gruber, D., Metka, M., Huber, J. Psychopharmacology (Berl.) (2005) [Pubmed]
  8. Immunity and beta-endorphin concentrations in hypothalamus and plasma in rats with steroid-induced polycystic ovaries: effect of low-frequency electroacupuncture. Stener-Victorin, E., Lindholm, C. Biol. Reprod. (2004) [Pubmed]
  9. Chronic administration of 4-tert-octylphenol to adult male rats causes shrinkage of the testes and male accessory sex organs, disrupts spermatogenesis, and increases the incidence of sperm deformities. Boockfor, F.R., Blake, C.A. Biol. Reprod. (1997) [Pubmed]
  10. Relation of myeloperoxidase promoter polymorphism and long-term hormone replacement therapy to oxidized low-density lipoprotein autoantibodies in postmenopausal women. Mäkelä, R., Dastidar, P., Jokela, H., Jaakkola, O., Saarela, M., Punnonen, R., Lehtimäki, T. Scand. J. Clin. Lab. Invest. (2006) [Pubmed]
  11. Estrus and pregnancy rates following synchronization with chronolone intravaginal sponge or norgestomet ear implant in cycling ewes. Spitzer, J.C., Carpenter, R.H. Theriogenology (1981) [Pubmed]
  12. Alleviation of the climacteric symptoms with oral sequential hormone replacement therapy. Chittacharoen, A., Domhardt, R., Manonai, J., Theppisai, U., Golbs, S. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. (2004) [Pubmed]
  13. Estrogen-induced impairments as a mechanism in reproductive senescence of female C57BL/6J mice. Mobbs, C.V., Finch, C.E. Journal of gerontology. (1992) [Pubmed]
  14. Estrogen-induced abnormal accumulation of fat cells in the rat penis and associated loss of fertility depends upon estrogen exposure during critical period of penile development. Goyal, H.O., Braden, T.D., Williams, C.S., Dalvi, P., Mansour, M., Williams, J.W. Toxicol. Sci. (2005) [Pubmed]
  15. Estrogen effects on the tuberoinfundibular dopaminergic system in the female rat brain. Jones, E.E., Naftolin, F. Brain Res. (1990) [Pubmed]
  16. Ovarian expression of alpha (1)- and beta (2)-adrenoceptors and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries. Manni, L., Holmäng, A., Lundeberg, T., Aloe, L., Stener-Victorin, E. Autonomic neuroscience : basic & clinical. (2005) [Pubmed]
  17. Effect of four different oral contraceptives on various sex hormones and serum-binding globulins. Wiegratz, I., Kutschera, E., Lee, J.H., Moore, C., Mellinger, U., Winkler, U.H., Kuhl, H. Contraception. (2003) [Pubmed]
  18. Effects of a new estrogen/progestin combination in the treatment of postmenopausal syndrome. Gambacciani, M., Spinetti, A., Orlandi, R., Piaggesi, L., Cappagli, B., Weiss, C., Ciaponi, M., Genazzani, A.R. Maturitas. (1995) [Pubmed]
  19. Effect of electro-acupuncture on ovarian expression of alpha (1)- and beta (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries. Manni, L., Lundeberg, T., Holmäng, A., Aloe, L., Stener-Victorin, E. Reprod. Biol. Endocrinol. (2005) [Pubmed]
  20. A role of estrogens and insulin binding in the dietary lipid alteration of R3230AC mammary carcinoma growth in rats. Feldman, J.M., Hilf, R. Cancer Res. (1985) [Pubmed]
  21. Effect of estrogen on pressor responses to alpha1-adrenoreceptor agonist in conscious female rats. Minami, N., Mori, N., Nagasaka, M., Kurosawa, H., Kanazawa, M., Kohzuki, M. Hypertens. Res. (2002) [Pubmed]
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