Behav Neurosci. 2002 Apr;116(2):198-205.
Estradiol induces hypothalamic progesterone receptors but does not activate mating behavior in male hamsters (Mesocricetus auratus) before puberty.

Romeo RD, Wagner CK, Jansen HT, Diedrich SL, Sisk CL.

Department of Psychology, Michigan State University, East Lansing 48824, USA.

This study investigated pubertal changes in neural and behavioral responses to estradiol. Gonadectomized pre- and postpubertal male hamsters (Mesocricetus auratus) were treated with 0.00, 0.05, 0.10, or 0.25 mg estradiol and tested 1 week later for sexual behavior with a receptive female. Estradiol activated behavior in postpubertal, but not prepubertal, males. In contrast, estrogen receptor alpha (ERalpha) and progesterone receptor (PR) immunoreactivity in forebrain nuclei that mediate mating behavior was similar in pre- and postpubertal males. Thus, absence of a behavioral response before puberty is not associated with reduced levels of steroid receptors. Because estradiol induced PR in prepubertal males, these data also suggest that ERa is functional before puberty. Therefore, gonadal steroids facilitate male reproductive behavior only after as-yet-unidentified developmental processes occur during puberty.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11996305&dopt=Abstract estradiol




Arch Gynecol Obstet. 2002 Jan;266(1):18-20.
Relationship of follicle number, serum estradiol level, and other factors to clinical pregnancy rate in gonadotropin-induced intrauterine insemination cycles.

Ozcakir HT, Goker EN, Terek MC, Adakan S, Ulukus M, Levi R, Tavmergen E.

Family Planning and Infertility Resarch and Treatment Center, Ege University, Bornova, Izmir, Turkey.

OBJECTIVE: To determine the characteristics associated with clinical pregnancy rate after gonadotropin-induced intrauterine insemination cycles in patients without male or tubal factor infertility. MATERIALS AND METHODS: One hundred and eighty patients undergoing controlled ovarian hyperstimulation followed by intrauterine insemination were included in the study retrospectively. The patients' files were retrospectively evaluated with respect to age, number of follicles, endometrial thickness and serum hormone levels at baseline and at the day of human chorionic gonadotropin (hCG) administration. The patients with male or unilateral tubal factor infertility were excluded from the study. RESULTS: The serum estradiol level at the day of hCG administration was not correlated with the clinical pregnancy rate (r=-0.05, p=0.481). The number of follicles was not correlated with the clinical pregnancy rate (r=-0.09, p=0.209). There was no significant difference between the clinically pregnants (n=32) and not pregnants (n=148) regarding the mean age, baseline serum levels of luteinizing hormone (LH) and estradiol, serum estradiol and LH levels at the day of hCG administration and endometrial thickness (p>0.05). Although not statistically significant, a pregnancy rate of 14.2% with less than 3 follicles > or = 18 mm is present compared to a pregnancy rate of 27.5% with at least 3 follicles > or = 18 mm and 24% with > or = 4 follicles > or = 18 mm. CONCLUSION: The clinical pregnancy rate does not seem to be affected with the number of follicles present at the time of intrauterine insemination or the serum estradiol level




J Neuroendocrinol. 2002 Mar;14(3):175-83.
Regulation and expression of progesterone receptor mRNA isoforms A and B in the male and female rat hypothalamus and pituitary following oestrogen treatment.

Scott RE, Wu-Peng XS, Pfaff DW.

Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA. rscotelicontherapeutics.com

Progesterone receptors play a central role in neuroendocrine and behavioural regulation. To gain insight into the sex- and tissue-specific regulation of progesterone receptors, protein binding on a progesterone receptor-oestrogen response element and mRNA levels for progesterone receptor (PR)-A and PR-B were compared between female and male rats following oestradiol benzoate replacement treatment in hypothalamic and pituitary tissue. Both male and female pituitary protein extracts demonstrated an increase in nuclear protein binding activity to a progesterone receptor-oestrogen response element following oestradiol benzoate treatment. However, there was a greater difference in total binding activity seen in the female pituitary extracts compared to male pituitary protein extracts. In both cases, reflecting the binding data, oestradiol benzoate pretreatment led to an increase in pituitary PR-B messenger RNA, although this increase was significantly larger in females than in males. Oestradiol benzoate treatment also led to a significant increase in specific binding of hypothalamic nuclear proteins to the progesterone receptor oestrogen response element from both females and male hypothalamic extracts. In addition, PR-B messenger RNA was induced by oestradiol benzoate treatment in the female rat hypothalamus, under circumstances where no PR-A could be detected. The male also demonstrated an increase in PR-B messenger RNA following oestradiol benzoate treatment, with undetectable levels of PR-A, although to a lesser degree than that seen in the female. The predominance of PR-B over PR-A messenger RNA in rat hypothalamus and pituitary, and the quantitati




J Neuroendocrinol. 2002 Mar;14(3):200-6.
Effect of adrenergic blockade on the pheromonal restoration of cyclic activity in young oestrogen-primed persistent oestrous female rats.

Mora A, Sanchez-Criado JE.

Departamento de Fisiologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain. moraned.ucm.es

The effects of adrenergic blockade on pheromonal restoration of cyclic activity were studied in acute oestrogenized persistent oestrous young female rats. Hypothalamic luteinizing hormone-releasing hormone (LHRH) and plasma LH, follicle-stimulating hormone (FSH), oestradiol and progesterone were measured by specific radio-immunoassays, and prolactin by enzyme-linked immunosorbent assay in: (i) young cycling rats; (ii) young persistent oestrous female rats; (iii) young persistent oestrous females treated with nasal sprays of male urine; and (iv) young persistent oestrous females treated with nasal sprays of male urine and injected with saline, propranolol, prazosin or yohimbine. LHRH was low 24 h after oestradiol benzoate injection, increasing up to 15 days later; LH, FSH, oestradiol and progesterone ranged from high values 24 h after oestradiol benzoate injection to low 15 days later; prolactin ranged from low concentration 24 h after oestradiol benzoate injection to high 15 days later. Male urine treatment induced a depletion of LHRH, a rise of LH, FSH and progesterone, pheromonal restoration of cyclic activity and a normal hormonal cyclic pattern. Treatment with prazosin and yohimbine prevented the pheromonal restoration of cyclic activity, the drop of LHRH and the rise of plasma concentration of the studied hormones induced by male urine, while saline or propranolol did not. These results show the hormonal pattern of the pheromonal restoration of cyclic activity in persistent oestrous rats and strongly suggest that alpha-adrenergic inputs to the hypothalamus may be involved in this pheromonal effect.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11999719&dopt=Abstract estradiol




Alcohol. 2002 Feb;26(2):103-13.
Ethanol consumption in the female Long-Evans rat: a modulatory role of estradiol.

Ford MM, Eldridge JC, Samson HH.

Center for the Neurobehavioral Study of Alcohol, Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA. mforfubmc.edu

The examination of various gonadal hormone manipulations on ethanol intake in human subjects and in rodent models has resulted in disparate findings. In the present study, we examined the effects of ovariectomy and subsequent estradiol (E(2)) replacement on ethanol intake in a within-subject design, as well as assessed the relevance of reproductive status on the efficacy of an E(2) stimulus in eliciting consumption. Female Long-Evans rats (n = 24) were given access to 10% ethanol and water in a continuous-access paradigm. After establishment of baseline intake values, rats were divided into four groups: sham/placebo (Shm+P), sham/estradiol (Shm+E(2)), ovariectomized/placebo (Ovx+P), and ovariectomized/estradiol (Ovx+E(2)). Rats in the Ovx+P group were found to have a large and permanent decline in ethanol intake that persisted more than 3 months postsurgery. Administration of E(2) to Ovx+E(2) rats was associated with restoration of ethanol consumption to baseline levels. When Shm+E(2) and Ovx+E(2) groups were compared, reproductive status was found to be a determining factor in the efficacy of E(2) to elicit ethanol intake. Together, these findings provide evidence that ovarian hormones, particularly estradiol, exert activational effects on estrogen-responsive substrates to modulate ethanol consumption in the adult female rat.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12007585&dopt=Abstract estradiol




Life Sci. 2002 May 17;70(26):3109-21.
Effect of lignans isolated from Hernandia nymphaeifolia on estrogenic compounds-induced calcium mobilization in human neutrophils.

Chao YY, Jan CR, Ko YC, Chen JJ, Jiann BP, Lu YC, Chen WC, Su W, Chen IS.

Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University, 807, Kaohsiung, Taiwan.

The effect of five lignans isolated from Hernandia nymphaeifolia on estrogenic compounds (17beta-estradiol, tamoxifen and clomiphene)-induced Ca(2+) mobilization in human neutrophils was investigated. The five lignans were epi-yangambin, epi-magnolin, epi-aschantin, deoxypodophyllotoxin and yatein. In Ca(2+)-containing medium, the lignans (50-100 microM) inhibited 10 microM 17beta-estradiol- and 5 microM tamoxifen-induced increases in intracellular free Ca(2+) levels ([Ca(2+)](i)) without changing 25 microM clomiphene-induced [Ca(2+)](i) increase. 17beta-estradiol and tamoxifen increased [Ca(2+)](i) by causing Ca(2+) influx and Ca(2+) release because their responses were partly reduced by removing extracellular Ca(2+). In contrast, clomiphene solely induced Ca(2+) release. The effect of the lignans on these two Ca(2+) movement pathways underlying 17beta-estradiol- and tamoxifen-induced [Ca(2+)](i) increases was explored. All the lignans (50-100 microM) inhibited 10 microM 17beta-estradiol-and 5 microM tamoxifen-induced Ca(2+) release, and 17beta-estradiol-induced Ca(2+) influx. However, only 100 microM epi-aschantin was able to reduce tamoxifen-induced Ca(2+) influx while the other lignans had no effect. Collectively, this study shows that the lignans altered estrogenic compounds-induced Ca(2+) signaling in human neutrophils in a multiple manner.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12008094&dopt=Abstract estradiol




J Cancer Res Clin Oncol. 2003 Apr;129(4):245-9. Epub 2003 Apr 15.
Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer.

Berstein LM, Tchernobrovkina AE, Gamajunova VB, Kovalevskij AJ, Vasilyev DA, Chepik OF, Turkevitch EA, Tsyrlina EV, Maximov SJ, Ashrafian LA, Thijssen JH.

Lab. Oncoendocrinology, N.N. Petrov Research Institute of Oncology, Pesochny-2, 197758, St. Petersburg, Russia. levmndocrin.spb.ru

OBJECTIVES: To compare estrogen concentrations in endometrial cancer tissue with those in macroscopically normal endometrium and with certain morphological characteristics of the tumor and endocrine parameters in patients. METHODS: The estradiol content was evaluated by radioimmunoassay after homogenization and extraction in 78 adenocarcinomas (61 from postmenopausal patients). RESULTS: Higher concentrations of estradiol in tumor tissue samples than in macroscopically normal endometrium were found in patients of both reproductive and postmenopausal age. This difference was the same in patients with either endometrial carcinoma type I or type II. No association between tumor steroid receptor levels, estradiol concentrations in blood serum, and timing of menopause with intratumoral estradiol contents was discovered. Estradiol concentrations in tumor tissues correlated positively with the clinical stage of disease and rate of tumor invasion (in patients with peripheric/lower type of fat topography), and negatively with tumor differentiation stage (in patients with central/upper type of fat topography) and the percentage of intact double-stranded DNA in normal endometrium. CONCLUSIONS: Tumor estrogen content in endometrial cancer has clinical significance that is modified in the presence of certain endocrine characteristics related to insulin resistance. The role of local estrogen production (aromatase activity) in this setting deserves special study.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12695909&dopt=Abstract estradiol




Toxicol Sci. 2002 Jun;67(2):264-74.
2,3,7,8-tetrachlorodibenzo-p-dioxin interacts with endogenous estradiol to disrupt prostate gland morphogenesis in male rat fetuses.

Timms BG, Peterson RE, vom Saal FS.

Division of Basic Biomedical Sciences, School of Medicine, University of South Dakota, 414 East Clark Street, Vermillion, SD 57069, USA. btimmsd.edu

Fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with normal development of the male reproductive system in rats and mice. We examined the effects of TCDD on the initial development of the urogenital system (urethra, prostate, and seminal vesicles) in male rat fetuses on gestation day (GD) 20. The number of prostatic buds and size of prostate glands as well as seminal vesicle size was determined by computer-assisted 3D reconstruction. Pregnant Holtzman rats received a single oral dose of TCDD (1 microg/kg) on GD 15. The intrauterine position (IUP) of male fetuses was identified based on the sex of adjacent fetuses: 2F males were located between 2 females and 2M males were located between 2 males. Control 2F males had elevated serum estradiol and larger prostates than control 2M males, which had elevated serum testosterone and larger seminal vesicles, confirming prior findings. There was no effect of TCDD on serum testosterone. TCDD significantly decreased the number of buds in the dorsocranial and dorsolateral regions of the urogenital sinus and overall prostate size, and was associated with a significant decrease in serum estradiol only in 2F males. In contrast, in 2M males both serum estradiol and the number and size of prostatic buds in these same regions of the prostate were unaffected by TCDD, although seminal vesicle size was reduced. These findings show that individual differences in gonadal steroid levels influence the response of the developing prostate to TCDD in male fetuses. In addition, these TCDD effects may be mediated in part by a decrease in serum estradiol levels.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12011486&dopt=Abstract estradiol [PubMed -




J Hypertens. 2002 May;20(5):1001-6.
Oestrogen action on the myocardium in vivo: specific and permissive for angiotensin-converting enzyme inhibition.

Pelzer T, de Jager T, Muck J, Stimpel M, Neyses L.

Department of Medicine, University of Wurzburg, Wurzburg, Germany. t.pelzeedizin.uni-wuerzburg.de

OBJECTIVES : In contrast to the vasculature, it remains unclear whether oestrogens also directly affect the myocardium. In this study, we addressed basic questions regarding oestrogen effects on the myocardium, including specificity, pathophysiological relevance and potential clinical implications, with a special focus on interactions between oestrogen and angiotensin-converting enzyme (ACE) inhibitors in an established in-vivo model of cardiac hypertrophy. METHODS AND RESULTS : Female spontaneously hypertensive rats (SHR) were ovarectomized (OVX) or sham-operated and treated with 17beta-oestradiol (2 microg/kg per day subcutaneously), the oestrogen receptor antagonist ZM-182780 (250 microg/kg per day subcutaneously) and the ACE-inhibitor moexipril (10 mg/kg per day orally) alone or in combination for 3 months. Hormone replacement restored physiological oestradiol serum levels and prevented uterus atrophy. Whereas moexipril alone was ineffective in OVX rats, substitution of oestradiol restored the beneficial effect of moexipril on systolic blood pressure (-30 +/- 5 mmHg) and relative heart weight (-11 +/- 3%) in OVX rats. Oestradiol upregulated alpha-myosin heavy chain (MHC) mRNA (+37 +/- 7%) and protein expression (+43 +/- 6%) in spite of increased blood pressure in OVX rats. Simultaneous treatment with oestradiol plus moexipril most effectively shifted the ratio of alpha-/beta-MHC mRNA and protein expression towards alpha-MHC in OVX animals. Oestradiol (10 nmol/l) also upregulated alpha-MHC mRNA and protein in cultured cardiac myocytes. The oestrogen receptor antagonist ZM-182780 significantly inhibited the observed oestrogen effects. CONCLUSIONS : Oestrogen replacement is permissive for