Estrogen - the female sexual hormone playing the most important role - plays a physiologically significant role, not only regulating in cell signals with second messenger but also being active in regulating transcription. Estrogen receptor (ER) which is a protein accepting estrogen not only play the role of a transcription factor combining with other genes to regulate their activity like other nuclear receptors but also performs external activities, combining with DNA, etc. G-protein coupled ER (GPER) that has been recently discovered exists as 7-membrane and has non-genomic (rapid) signaling. These functions, however, are not extensively addressed. This paper discusses the roles of GPER and its physiological mechanism.
DNA ; Estradiol ; Estrogens* ; Female ; Genomics ; GTP-Binding Proteins* ; Humans ; Receptors, Cytoplasmic and Nuclear ; Second Messenger Systems ; Transcription Factors ; Women's Health*

OBJECTIVE: There is increasing evidence for the expression of rat LH gene in several extrapituitary sites including testis and ovary. We also have demonstrated that the local LH expression in the rat epididymis and uterus, the major accessory sex organs in male and female reproductive system, respectively. DESIGN: The present study was undertaken to elucidate whether the gene for LH receptor is expressed in rat uterus and whether the expression of uterine LH and its receptor are differentially regulated during estrous cycle. Presence of the transcripts for rat LH receptor in the rat uterine tissue were confirmed by touchdown reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In LHbeta semi-quantitative RT-PCR, the highest expression level was shown in estrus stage. The level of LH receptor transcripts was also fluctuated during estrous cycle. In ovariectomized rats (OVX + Oil), the expressions of both uterine LH and LH-R were markedly reduced when compared to those from normal rats. Supplement with estradiol 17beta to the ovariectomized rats (OVX + E2) restored the expression levels of LH and its receptor to the levels in uteri from normal rats. CONCLUSION: Our findings indicated that 1) LH and its receptor gene are expressed in the rat uterus from cycling rats, 2) the expression of uterine LH and its receptor is mainly, if not all, under the control of ovarian sex steroid(s). These results suggested that the uterine LH may act as a local regulator with auto and/or paracrine manner, though the posibility that the pituitary LH may act directly on the regulation of uterine functions could not be discarded.
Animals ; Epididymis ; Estradiol ; Estrous Cycle ; Estrus ; Female ; Genitalia ; Humans ; Lutein* ; Luteinizing Hormone* ; Male ; Ovary ; Rats* ; Receptors, LH ; Testis ; Uterus*

A rapid decline in egg production of laying hens begins after 480 d of age. Such a rapid decrease results predominantly from the ovarian aging, accompanied by endocrine changes, decreased yolk synthesis and accumulation, and the reduction in follicles selected into the preovulatory hierarchy. In this study, hens at 90, 150, 280, and 580 d old (D90, D150, D280, and D580, respectively) were compared for yolk precursor formation in the liver to elucidate effects of aging on laying performance. The results showed that liver lipid synthesis increased remarkably in hens from D90 to D150, but decreased sharply at D580 as indicated by the changes in triglyceride (TG) levels. This result was consistent with the age-related changes of the laying performance. The levels of liver antioxidants and total antioxidant capacity decreased significantly in D580 hens and the methane dicarboxylic aldehyde in D580 hens was much higher than that at other stages. The serum 17β-estradiol level increased from D90 to D280, but decreased at D580 (P<0.05). The expression of estrogen receptor α and β mRNAs in the liver displayed similar changes to the serum 17β-estradiol in D580 hens. Expressions of the genes related to yolk precursor formation and enzymes responsible for fat acid synthesis were all decreased in D580 hens. These results indicated that decreased yolk precursor formation in the liver of the aged hens resulted from concomitant decreases of serum 17β-estradiol level, transcription levels of estrogen receptors and critical genes involved in yolk precursor synthesis, and liver antioxidant status.
Age Factors ; Animals ; Antioxidants ; metabolism ; Chickens ; Egg Yolk ; metabolism ; Estradiol ; blood ; Female ; Lipids ; biosynthesis ; Liver ; metabolism ; Oviposition ; Receptors, Estrogen ; genetics

Estrogen receptors localized to many sites within the cell are giving comprehensive contribution to estrogen functions. In recent years, researches have identified that some estrogen receptors are localized to the plasma membrane, while other estrogen receptors exist in cytoplasm besides nucleus. Cross-talk occurs between extra-nuclear estrogen receptor and nuclear estrogen receptor signalings. The integration of estrogen and its receptor actions from different sites within the cell leads to the rapid and prolonged actions of estrogen, thus they produce important biological functions in the sex organ and other organs.
Animals ; Cell Membrane ; metabolism ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Estrogens ; metabolism ; physiology ; Humans ; Receptors, Estradiol ; metabolism ; Receptors, Estrogen ; metabolism ; Signal Transduction

PURPOSE: Diabetes profoundly and negatively impacts all domains of female sexual function, however, the underlying pathophysiological mechanisms remain unknown. To date, limited studies have been published on the effects of type 1 & type 2 diabetes on female genital sexual arousal and how this may impact overall sexual function. The aim of this review is to discuss the effects of diabetes on female sexual function and insights from laboratory studies on the underlying pathophysiology. MATERIALS AND METHODS: Using PubMed, we reviewed and evaluated the literature published between 1970 and 2009 and data from our laboratories and others investigating the effects of type 1 and type 2 diabetes on genital sexual arousal responses. RESULTS: Women with diabetes experience diminished genital arousal, reduced vaginal lubrication, vaginal atrophy, dyspareunia, and increased vaginal infections. Also, a number of studies using type 1 and type 2 diabetic animal models have reported reduced plasma estradiol levels and marked physiological, biochemical and histological changes in genital tissues. In animal studies, diabetes alters genital tissue structure and attenuates expression of the estrogen, progesterone and androgen receptors and alters vaginal and clitoral hemodynamics. Importantly, treatment of diabetic animals with estradiol in the face of persistent hyperglycemia can restore vaginal structure and sex steroid receptor expression. CONCLUSIONS: Type 1 & type 2 diabetic complications produce significant structural and functional disruptions in genital organs and attenuate genital hemodynamics. In the type 2 animal model, estradiol treatment ameliorates diabetic-induced pathophysiological alterations in genital tissues, such as the vagina. This suggests that estrogen supplementation may be beneficial in restoring diabetes-induced genital pathology.
Animals ; Arousal ; Atrophy ; Clitoris ; Diabetes Complications ; Diabetes Mellitus ; Dyspareunia ; Estradiol ; Estrogens ; Female ; Genitalia ; Hemodynamics ; Humans ; Hyperglycemia ; Lubrication ; Models, Animal ; Plasma ; Progesterone ; Receptors, Androgen ; Receptors, Steroid ; Testosterone ; Vagina

OBJECTIVETo observe the effect of Ruxian Pill I (RXP I) on mammary gland hyperplasia (MGH) in rabbits and to explore its mechanism.

METHODSSixty rabbits were divided into the high, medium and low dose of RXP I groups, the Xiaoyao Pill (XYP) group, the model group and the normal control group with 10 in each group. The former 5 groups were injected with diethylstilbestrol and progesterone intramuscularly for one month to induce the MGH model and then given respective medicines via gastrogavage for 3 months. The changes in morphology of mammary gland were observed using light and electronic microscope, the levels of estradiol (E2) and progestogen (P) were measured by radioimmunoassay, and the expression of estradiol receptor (ER) and progestogen receptor (PR) were detected with immunohistochemistry before, at the end of and 3 months after the treatment.

RESULTSCompared with those before treatment and those in the model group, in the high and midium dose of RXP I groups after treatment, obvious decrease of acini number in hyper-plastic lobuli mammae, connective tissues and blood capillaries, layers of glandular epithelium cells and organellers were seen with partial of hyperplastic cell apoptosis in them. Besides, the serum E2 level decreased obviously (P < 0.05), while the serum P level increased, and the ER expression down-regulated significantly (P < 0.05), but no obvious changes of PR expression was found. Three months later, all the above indexes maintained stable without rebound.

CONCLUSIONRXP I treatment could alleviate the hyperplasia of mammary glands, reduce E2 level, and down-regulate ER expression in rabbits with MGH, showing a significant therapeutical effect.

Animals ; Diethylstilbestrol ; Drugs, Chinese Herbal ; therapeutic use ; Estradiol ; blood ; Female ; Hyperplasia ; blood ; chemically induced ; prevention & control ; Immunohistochemistry ; Mammary Glands, Animal ; drug effects ; metabolism ; pathology ; Phytotherapy ; Progesterone ; Progestins ; blood ; Rabbits ; Radioimmunoassay ; Receptors, Estradiol ; analysis

PURPOSE: We evaluated the feasibility of non-invasive imaging of estrogen receptors (ER) in primary breast cancer with iodine-123-labeled ER specific ligand (17alpha,20E)-21-[123I] iodo-19-nonpregna-1,3,5-(10), 20-tetraene-3, 17-diol using conventional nuclear medicine technique. METHODS: Before they underwent surgical management, planar scintigraphy and single-photon emission computed tomography (SPECT) were performed in 18 patients with proven primary breast cancer, after single IV injection of 5~10 mCi I-123-estradiol. The results were compared with those of immunohistochemical staining against ER of the surgical specimens. RESULTS: Planar and SPECT imaging showed hot uptake in nine of eighteen (50%) breast cancer patients. The results of ER immunohistochemistry were all positive in these patients. In the 9 cases of negative scintigraphy, 8 showed negative staining results but one showed positive staining results. Therefore, the overall concordance rate of ER scintigraphy and ER immunohistochemistry was 94.4% (17/18). CONCLUSION: ER scintigraphy using I-123-estradiol is a highly predictable in vivo technique to detect ER-positive breast cancer preoperatively. It has potential application as a reliable diagnostic modality and indicator of hormone therapy for breast cancer patients.
Breast Neoplasms* ; Breast* ; Estradiol* ; Estrogens* ; Humans ; Immunohistochemistry ; Negative Staining ; Nuclear Medicine ; Radionuclide Imaging ; Receptors, Estrogen* ; Tomography, Emission-Computed ; Tomography, Emission-Computed, Single-Photon

PURPOSE: We evaluated the feasibility of non-invasive imaging of estrogen receptors (ER) in primary breast cancer with iodine-123-labeled ER specific ligand (17alpha,20E)-21-[123I] iodo-19-nonpregna-1,3,5-(10), 20-tetraene-3, 17-diol using conventional nuclear medicine technique. METHODS: Before they underwent surgical management, planar scintigraphy and single-photon emission computed tomography (SPECT) were performed in 18 patients with proven primary breast cancer, after single IV injection of 5~10 mCi I-123-estradiol. The results were compared with those of immunohistochemical staining against ER of the surgical specimens. RESULTS: Planar and SPECT imaging showed hot uptake in nine of eighteen (50%) breast cancer patients. The results of ER immunohistochemistry were all positive in these patients. In the 9 cases of negative scintigraphy, 8 showed negative staining results but one showed positive staining results. Therefore, the overall concordance rate of ER scintigraphy and ER immunohistochemistry was 94.4% (17/18). CONCLUSION: ER scintigraphy using I-123-estradiol is a highly predictable in vivo technique to detect ER-positive breast cancer preoperatively. It has potential application as a re-liable diagnostic modality and indicator of hormone therapy for breast cancer patients.
Breast Neoplasms* ; Breast* ; Estradiol* ; Estrogens* ; Humans ; Immunohistochemistry ; Negative Staining ; Nuclear Medicine ; Radionuclide Imaging ; Receptors, Estrogen* ; Tomography, Emission-Computed ; Tomography, Emission-Computed, Single-Photon

BACKGROUND: The loss of estrogen and progesterone receptors appears to be associated with a progression to less-differentiated and hormone-independent tumors. The gain of hormone independency over time even in estrogen receptor-positive tumors has become another obstacle to endocrine therapy for breast cancer. We tried to regain the hormone dependency in estrogen receptor-negative breast cancer cells by lipofecting estrogen receptor cDNA. MATERIALS AND METHODS: The mutant human estrogen receptor cDNA (pSG5-HE0) was lipofected into estrogen receptor-negative human breast cancer cell line MDA-MB-231, in an attempt to restore their sensitivity to antiestrogen. Then the effects if 17 beta -estradiol and tamoxifen were studied by counting viable cell numbers after treating the lipofected cell line with either one or together. RESULTS: The cell growth was most profoundly inhibited in 4 days after lipofection with mutant human estrogen receptor cDNA, which was overcome after that days. Tamoxifen, as an antiestrogen, showed a growth inhibitory effect slightly strong over combined conditions of tamoxifen and 17 beta estradiol compared to estrogen-treated group and to control. CONCLUSIONS: The temporary induction of estrogen receptor by lipofection with pSG5-HE0 on estrogen receptor-negative human breast cancer cell line MDA-MB-231 showed negative growth control on these cells by tamoxifen, indicating that liposome-mediated estrogen receptor transfection may be used as a novel therapeutic strategy for hormone independent human breast cancers in the near future.
Breast Neoplasms* ; Breast* ; Cell Count ; Cell Line ; DNA, Complementary ; Estradiol ; Estrogen Receptor Modulators ; Estrogens* ; Genetic Therapy ; Humans* ; Receptors, Progesterone ; Tamoxifen* ; Transfection

OBJECTIVE: To investigate the association of FSH receptor (FSHR) polymorphism at position 680 with outcomes of controlled ovarian hyper-stimulation for IVF-ET in Korean women. Design: Genetic polymorphism analysis. MATERIALS AND METHODS: The FSHR polymorphism was analyzed by PCR-RFLP in 172 ovulatory women below the age of 40 year. Patients with polycystic ovary syndrome, endometriosis, or previous history of ovarian surgery were excluded. RESULTS: Genotype distribution was 41.9% for the Asn/Asn, 47.7% for the Asn/Ser, and 10.5% for the Ser/Ser FSHR genotype group. There was no difference in age of subjects and infertility diagnosis between genotype groups. When the patients were grouped according to their FSHR genotype, the basal levels of FSH (day 3) were significantly different among the three groups (6.0+/-0.3 IU/L (mean+/-SEM), 5.8+/-0.3 IU/L, and 8.6+/-1.2 IU/L for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, p=0.002). The Ser/Ser group showed a higher total doses of gonadotropins required to achieve ovulation induction, and a lower serum estradiol levels at the time of hCG administration compared with other two groups, but the differences were of no statistical significance. The numbers of oocytes retrieved were significantly different among the three groups (8.6+/-0.8, 9.9+/-0.6, and 6.3+/-0.9, for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, p=0.049). Clinical pregnancy rates were 42.4%, 25.9%, and 29.4% for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. CONCLUSION: Homozygous Ser/Ser genotype of FSHR polymorphism at position 680 was associated with decreased ovarian response to gonadotropin stimulation for IVF-ET.
Diagnosis ; Embryo Transfer* ; Embryonic Structures* ; Endometriosis ; Estradiol ; Female ; Fertilization* ; Follicle Stimulating Hormone* ; Genotype ; Gonadotropins ; Humans ; Infertility ; Oocytes ; Ovulation Induction ; Polycystic Ovary Syndrome ; Polymorphism, Genetic ; Pregnancy Rate ; Receptors, FSH*