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

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

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

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: The purpose of this study was to evaluate the effects of estrogen on detrusor contraction and the expression of muscarinic receptors in ovariectomized rats. MATERIALS AND METHODS: 24 Sprague-Dawley female virgin rats(12 weeks old) were separated into three groups of 8 rats each. Group I served as a control group, group II was the ovariectomized only rats(Ovx group) and Group III was given estradiol benzoate(0.8mg/kg/day) subcutaneously for 7 consecutive days, beginning 1 week after ovariectomy(Ovx+E group). At the end of the experimental period, each rat was sacrificed and the urinary bladder was removed for contractile studies. The expressions of M2 and M3 receptors in the bladder epithelium and the muscle layer were investigated by performing immunofluorescent staining. RESULTS: The Ovx group showed a significantly decreased bladder contractile function on the KCl and carbachol-induced contractile tests, whereas the Ovx+E group showed increased contractility(p<0.05). The Ovx+E group showed an increase of smooth muscle compared to the other groups. Ovariectomy induced a significant increase in the M3 receptors density in the bladder body, as compared to the control group(p<0.05) but there was no significant difference between the Ovx group and the Ovx+E group. CONCLUSIONS: Bladder dysfunction of menopausal women is thought not to be related with the changes of muscarinic receptors. Our results suggest that the detrusor contractility of menopausal women might be improved after estrogen replacement therapy.
Animals ; Contracts ; Epithelium ; Estradiol ; Estrogen Replacement Therapy ; Estrogens ; Female ; Humans ; Muscle Contraction ; Muscle, Smooth ; Muscles ; Ovariectomy ; Rats ; Receptors, Muscarinic ; Urinary Bladder

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*

PURPOSE: The loss of estrogen and progesterone receptors appeats 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 estmgen receptor cDNA. MATERIALS AND METHODS: The mutant human estrogen receptor cDNA (pSGS-HEO) 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 of 17p-estradiol and tamoxifen were studied by counting viable cell numbers after treating the lipofected cell line with either one or together. RESULTS: Culture medium cantaining phenol red, a weak estrogen, has growth advantages compared with culture medium without it. In both culture conditions, cell growth was most profoundly inhibited in 4 days after lipofection with mutant human estrogen receptor cDNA, which was overcome after that day. Tamoxifen, as an antiestrogen, showed a growth inhibitory effect slightly stronger tban combined conditions of tamoxifen and 17- estradiol compared to estrogen-treated group and to control, and the inhibitory effect was lasted 4 days. CONCLUSION: The temporary induction of estrogen receptor by lipofection with pSGS-HEO 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 hormane 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* ; Phenolsulfonphthalein ; Receptors, Progesterone ; Tamoxifen ; Transfection

OBJECTIVE: To elucidate the location of leptin and receptors of ovary specimens obtained from patients undergoing hysterectomy by immunohistochemical staining and to determine the effect of leptin on the steroidogenesis of cultured granulosa cells. METHOD: In the culturing process of the granulosa cells, FSH (1 IU/ml)and leptin (50 ng/ml), IGF-I (50 ng/ml) was administered to each study group (Group I: FSH; Group II: FSH, leptin; Group III: FSH, IGF-I, leptin), and the levels of estradiol, progesterone, androstenedione in the culture media was measured by radioimmunoassay. Statistical analysis was conducted by one-way ANOVA with Scheffe test. RESULTS: The results showed that leptin and leptin receptors were both found to be strongly stained in granulosa and theca cells, and also in some interstitial cells. Leptin receptors were also observed in cultured granulosa cells. While there was no statistically significant difference in the androstnedione concentrations between the groups, estradiol concentrations was significantly decreased in Group IV (2202.0+/-151.14 pg/ml) compared to Group III (2859.0+/-122.6 pg/ml), and progesterone concentrations were also significantly decreased in Group II(4696.3+/-190.6 ng/ml) and Group IV (4517+/-206.78 ng/ml) compared to Group III(5546.0+/-179.5 ng/ml). CONCLUSTION: The study result of this study suggest that leptin is directly involved in the regulation of ovarian functions, in particular steroidogenesis.
Androstenedione ; Culture Media ; Estradiol ; Female ; Granulosa Cells* ; Humans* ; Hysterectomy ; Insulin-Like Growth Factor I ; Leptin* ; Ovary ; Progesterone ; Radioimmunoassay ; Receptors, Leptin ; Theca Cells