Theriogenology. 2001 Mar 15;55(5):1083-93.
Effects of estradiol-17beta administration on steady-state messenger ribonucleic acid (MRNA) encoding equine alpha and LH/CGbeta subunits in pituitaries of ovariectomized pony mares.

Sharp DC, Wolfe MW, Cleaver BD, Nilson J.

Animal Science Department, University of Florida, Gainesville 32611, USA. sharnimal.ufl.edu

The process of sexual recrudescence in the springtime in mares is characterized by renewal of follicular growth and acquisition of steroidogenic competence. Concomitant with renewal of follicular steroidogenesis is re-establishment of LH biosynthesis and secretion. Research results from our laboratory indicate that increased estradiol and LH secretion occur in close temporal association before the first ovulation of the year. Therefore, the hypothesis tested in this experiment was that estrogen administration to ovariectomized pony mares during the equivalent time of early vernal transition would enhance LH biosynthesis as monitored by messenger ribonucleic acid (mRNA) encoding for the pituitary subunits of LH (alpha and LH/CGbeta). Mares were administered either sesame oil vehicle control, or estradiol (5 mg i.m. twice daily in sesame oil) for 3, 6 or 9 days, beginning on February 2. The pituitary glands were harvested, and examined for LH subunit mRNA by Northern Blot and slot blot analysis. There was a significant increase in LH secretion after 6 days of estradiol secretion compared with control vehicle administration. Similarly, there was a significant increase in both alpha and LH/CGbeta subunit mRNA when estradiol was administered for 9 days. These data indicate that estrogen stimulates LH subunit formation in mares during early equivalent vernal transition. These data do not, however, discriminate between a direct pituitary effect of estrogen, and a hypothalamic effect. Whether the surge of estradiol just prior to the first ovulation of the year is essential for the renewed biosynthesis of LH subunits cannot be determined from the




J Cereb Blood Flow Metab. 2001 Apr;21(4):422-9.
Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca(2+) entry inhibition.

Salom JB, Burguete MC, Perez-Asensio FJ, Torregrosa G, Alborch E.

Research Center, University Hospital La Fe, Valencia University, Valencia, Spain.

Estrogens account for gender differences in the incidence and outcome of stroke, but it remains unclear to what extent neuroprotective effects of estrogens are because of parenchymal or vascular actions. Because reproductive steroids have vasoactive properties, the authors assessed the effects and mechanisms of action of 17-beta-estradiol in rabbit isolated basilar artery. Cumulative doses of 17-beta-estradiol (0.3 micromol/L to 0.1 mmol/L) induced concentration-dependent relaxation that was larger in basilar than carotid artery, in male than female basilar artery, and in KCl-precontracted than UTP-precontracted male basilar artery. Endothelium removal did not modify relaxation induced by 17-beta-estradiol in basilar artery, whereas relaxation induced by acetylcholine (1 nmol/L to 0.1 mmol/L) was almost abolished. Neither the estrogen receptor antagonist ICI 182,780 (1 micromol/L), nor the protein synthesis inhibitor cycloheximide (1 micromol/L) affected 17-beta-estradiol-induced relaxations. Relaxations induced by the K(+) channel openers NS1619 and pinacidil in the same concentration range were greater and lower, respectively, when compared with relaxation to 17-beta-estradiol, which was not significantly modified by incubation with the K(+) channel blockers charybdotoxin (1 nmol/L and 0.1 micromol/L) or glibenclamide (10 nmol/L and 1 micromol/L). Preincubation with 17-beta-estradiol (3 to 100 micromol/L) produced concentration-dependent inhibition of CaCl(2)-induced contraction, with less potency than the Ca(2+) entry blocker nicardipine (0.01 to 10 nmol/L). The authors conclude that 17-beta-estradiol induces endothelium-independent relaxation of cerebral arteries with tissue and gender selectivity. The relaxant




Brain Res. 2001 May 4;900(1):137-42.
Deleterious effect of beta-estradiol in a rat model of transient forebrain ischemia.

Harukuni I, Hurn PD, Crain BJ.

Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Estrogen has demonstrated great potential as a therapeutic agent in focal ischemic brain injury, as exogenous beta-estradiol has proven beneficial in a variety of focal stroke models. In contrast, the relatively few studies of estrogen's efficacy in transient forebrain ischemia have produced inconsistent results. The present study was therefore designed to clarify estrogen's neuroprotective potential in selective hippocampal neuronal injury resulting from four-vessel occlusion in the rat. Female Wistar rats (normal, ovariectomized, or ovariectomized and estradiol-treated) received 5 or 10 min of ischemia. No differences in hippocampal cell loss were found amongst the groups with 10 min of ischemia. Amongst the groups with 5 min of ischemia, the mildest injury was found in the ovariectomized animals, which lost only 32% of their CA1 pyramidal cells. In comparison, mean cell losses were 54% and 49%, respectively, in intact females and in ovariectomized animals with estradiol replacement. Linear regression analysis demonstrated a highly significant relationship between cell loss and plasma estradiol levels. The mechanism by which exogenous and endogenous estrogen exacerbated the injury is unclear, as estrogen has many neuroprotective effects. On the other hand, many other reported effects of estrogen in hippocampal area CA1 might confer increased sensitivity to ischemia, either by modulating the excitatory effects of glutamate or by modifying the inhibitory effects of GABA. Determining how to modulate the various competing effects of estrogen is of both theoretical and practical importance, as it is now clear that one cannot assume that estrogen administration will always improve outcome in cerebral ischemia.






Mol Cell Endocrinol. 2001 Apr 25;175(1-2):101-9.
The dissociation rate of estrogen receptor alpha from the consensus estrogen response element.

Szatkowski Ozers M, Hill JJ, Ervin K, Royer CA, Gorski J.

Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. maryanvera.com

The rate of dissociation of recombinant, purified human estrogen receptor alpha (ERalpha) from a fluorescein-labeled DNA containing the consensus vitellogenin ERE sequence (F-vitERE) was determined in real time using fluorescence anisotropy. The complex of estradiol-occupied ERalpha with F-vitERE had an apparent dissociation rate of 1.48+/-0.06x10(-2) s(-1) and a half-life of 46.6 s at room temperature. The dissociation rate was characterized by a single exponential decay, suggesting that ER dissociates from the DNA as a preformed dimer, rather than as two individual monomers. The association rate of estradiol-occupied ERalpha for the F-vitERE was calculated as 7x10(6) M(-1) s(-1) based on the dissociation rate measured and previous determinations of the equilibrium dissociation constant (Kd) in similar assay conditions (Ozers et al., 1997). In buffer containing various concentrations of salt, the rate of dissociation of estradiol-occupied ERalpha from F-vitERE was accelerated by increasing salt concentrations. Compared to estradiol-occupied ERalpha, the rate of dissociation of unoccupied ERalpha from the F-vitERE was very similar, indicating that estradiol occupancy does not affect the dissociation rate of ERalpha from the ERE.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11325520&dopt=Abstract estradiol




J Obstet Gynaecol Res. 2001 Feb;27(1):53-9.
Nitric oxide mediates inhibitory effect of interleukin-1beta on estrogen production in human granulosa-luteal cells.

Tobai H, Nishiya I.

Department of Obstetrics and Gynecology, Iwate Medical University, Japan.

OBJECTIVE: To investigate the effect of IL-1beta on NO production and steroidogenesis in human granulosa-luteal cells obtained from women undergoing in vitro fertilization procedures. SUBJECTS AND METHODS: To investigate the effect of IL-1beta, granulosa-luteal cells were cultured with various doses of IL-1beta (0, 0.05, 0.5, 5, 50, 100 ng/ml), IL-1beta (5 ng/ml) with NG-nitro-L-arginine-methyl ester (L-NAME), selective inhibitors of NOS, sodium nitroprusside (SNP), NO donors and Genistain, a tyrosine kinase inhibitor. RESULTS: IL-1beta induced a dose-dependent stimulation of NO production and inhibited the production of estradiol in a significant way in a dose-dependent manner. L-NAME significantly decreased NO production and increased the production of estradiol and progesterone. SNP significantly increased NO production and caused decreases in the production of both estradiol and progesterone. Genistain decreased NO production and significantly increased the production of estradiol and progesterone. Inducible NOS (iNOS) messenger RNA was present in granulosa-luteal cells before treatment with IL-1beta. CONCLUSIONS: IL-1beta stimulated NO production, and NO inhibited the production of estradiol.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11330732&dopt=Abstract estradiol




Hum Reprod. 2001 May;16(5):862-7.
Basal concentrations of oestradiol may predict the outcome of in-vitro maturation in regularly menstruating women.

Mikkelsen AL, Andersson AM, Skakkebaek NE, Lindenberg S.

The Fertility Clinic, Institute of Human Reproduction, 3 Fruebjergvej, DK-2100 Copenhagen and Department of Growth and Reproduction, Copenhagen University Hospital, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. aliconia.dk

Retrospectively it was examined whether the number of retrieved oocytes, the maturation rate and cleavage rate can be predicted in regularly menstruating women by the use of the following predictive variables on cycle day 3-4: the concentration of FSH, oestradiol, inhibin B and inhibin A in serum and and the number of ovarian follicles seen by vaginal ultrasound. The study included 132 consecutive aspirations in 100 women attending the clinic for in-vitro maturation due to male factor and/or tubal factor. Fifteen pregnancies were obtained after transfer in 83 cycles, giving a pregnancy rate of 15/132 (11%) per aspiration and 15/83 (18%) per transfer. The concentration of FSH and the number of follicles on day 3 predicted the number of oocytes retrieved, whereas these parameters did not predict the subsequent development of oocytes. No correlation was found between the inhibin B, inhibin A, oestradiol and the number of oocytes respectively. The group with a low concentration of oestradiol on cycle day 3 (threshold <200 pmol/l) (group 1, n = 106 cycles) had a significantly higher pregnancy rate compared to the group with a higher concentration (group 2, n = 26 cycles) (14 versus 0% per aspiration, P = 0.03). The group with a low concentration of oestradiol was subdivided according to the concentration of inhibin A. Group 1a: low inhibin A (threshold <10 pg/ml, n = 84 cycles) and group 1b: high inhibin A concentration (> or =10 pg/ml, n = 19). The pregnancy rate in group 1a (14/84, 17%) differed significantly from group 1b (0/19, 0%) (P = 0.03). It is concl




Hum Reprod. 2001 May;16(5):1037-45.
Oestrogenic potencies of Zeranol, oestradiol, diethylstilboestrol, Bisphenol-A and genistein: implications for exposure assessment of potential endocrine disrupters.

Leffers H, Naesby M, Vendelbo B, Skakkebaek NE, Jorgensen M.

Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. henrik.lefferiobase.dk

We have compared the oestrogenic potency of the synthetic oestrogen Zeranol, used as a growth promoter in meat production, and five related compounds, with the potency of 17beta-oestradiol, diethylstilboestrol (DES), genistein, and Bisphenol-A. The potency was assayed by analysing differences in expression levels of endogenous oestrogen-regulated genes in human MCF7 cells, treated with different concentrations of the compounds. Zeranol, 17beta-oestradiol and DES were about equally potent, genistein was four to six orders of magnitude less potent than 17beta-oestradiol but an order of magnitude more potent than Bisphenol-A. There were gene specific differences, the PS2 and TGFbeta3 genes were about equally sensitive to Zeranol, 17beta-oestradiol and DES whereas a down-regulation of MRG1/p35srj could be detected at fmol/l concentrations of Zeranol whereas 17beta-oestradiol was several orders of magnitude less potent. GST mu3 was sensitive to fmol/l concentrations of 17beta-oestradiol but much less sensitive to Zeranol and DES. The very high potency of Zeranol compared with other potential endocrine disrupters suggests that Zeranol intake from beef products could have greater impact on consumers than the amounts of the known or suspected endocrine disrupters that have been found in food. Since little data is available in man, there is an urgent need for reliable measurements of the concentration of Zeranol in human serum after ingestion of meat products from treated animals.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11331657&dopt=Abstract estradiol




Fertil Steril. 2001 May;75(5):871-7.
Magnitude and variability of sequential estradiol and progesterone concentrations in women using depot medroxyprogesterone acetate for contraception.

Clark MK, Sowers M, Levy BT, Tenhundfeld P.

College of Nursing, University of Iowa, Iowa City, Iowa 52242, USA. mary-clariowa.edu

OBJECTIVE: To describe the magnitude and variability of sequential serum estradiol and progesterone concentrations throughout one depot medroxyprogesterone (DMPA) injection interval. DESIGN: Prospective study.Setting: Family planning and women's health clinics. PATIENT(S): Thirty-one women, ages 19 to 46, using DMPA for contraception. INTERVENTION(S): Serum for estrogen and progesterone was collected weekly throughout one DMPA injection interval. MAIN OUTCOME MEASURE(S): Serum estradiol and progesterone concentrations; estradiol patterns produced from data plotted across the entire DMPA injection interval. RESULT(S): The average daily estradiol concentrations ranged from 7.9 to 69.1 pg/mL, with a mean of 18.9 +/- 12.9 and a median of 15.4 pg/mL. Average daily progesterone concentrations ranged from 0.14 to 1.1 ng/mL, with a mean of 0.40 +/- 0.19 ng/mL and a median of 0.36 ng/mL. Two general patterns of estradiol concentrations were identified. One pattern, observed in approximately one third of the participants, reflected estradiol concentrations that were extremely low (mean, 12.7 +/- 3.6 pg/mL; median, 13.4 pg/mL) and consistently flat across the DMPA injection interval. The second pattern, seen in the remaining participants, reflected estradiol concentrations that were higher (mean, 22.2 +/- 14.9 pg/mL; median, 17.3 pg/mL) and quite variable. CONCLUSION(S): This study demonstrated that estradiol concentrations were lower than the 40 to 50 pg/mL reported in most studies and, for the majority of women, varied substantially across the DMPA injection interval.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11334896&dopt=Abstract estradiol



Fertil Steril. 2001 May;75(5):942-6.
Regulation of human oviductin mRNA expression in vivo.

Briton-Jones C, Lok IH, Yuen PM, Chiu TT, Cheung LP, Haines C.

Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China. chrisbuhk.edu.hk

OBJECTIVE: To examine changes in oviductin mRNA expression in oviductal mucosal tissue from fertile women throughout an ovulatory cycle. DESIGN: Semiquantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis of oviductin mRNA. SETTING: University-based obstetrics and gynecology department. SUBJECT(S): Twenty women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids. INTERVENTION(S): The mucosal layer was isolated from the oviduct tissue, and semiquantitative RT-PCR was performed. MAIN OUTCOME MEASURE(S): The relationship between serum estradiol, luteinizing hormone, and progesterone concentrations and the expression of oviductin mRNA. RESULT(S): There was a significant positive correlation between serum estradiol and luteinizing hormone concentrations and oviductin mRNA expression. There was a significant inverse correlation between serum progesterone concentrations and oviductin mRNA expression. CONCLUSION(S): Little is known about the regulation of human oviductin. This study was the first to examine the relationship between oviductin mRNA expression and serum estradiol and luteinizing hormone and progesterone concentrations in fertile women. Estradiol and luteinizing hormone both have a stimulatory effect on oviductin mRNA in humans, however, it is difficult to determine whether the effects are independent of one another, as the luteinizing hormone surge is dependent on the estradiol increase. Progesterone shows a clear inhibitory effect on oviductin mRNA.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11334906&dopt=Abstract estradiol