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1.
Androgen receptors have been found in duck preen glands by using dextran-coated charcoal adsorption. They bound DHT with high affinity (KD = 0.2 nM), limited capacity (45 fmoles/mgP) and good specificity. They sedimented at 8 S in a sucrose gradient and were destroyed by pronase digestion and heating. An estrogen receptor having different binding specificity was also demonstrated. On the basis of a marked annual cycle of gonadal activity in ducks, this system appears appropriate for studying the regulation of sex steroid hormone receptors. 相似文献
2.
Sucrose gradient studies of rat pineal cytosol incubated with 3H-estradiol (female pineals) or 3H-5 α -dihydrotestosterone (male pineals) revealed a radioactivity peak in the 8 S region which disappeared after superior cervical ganglionectomy or incubation with excess unlabeled hormone. Ganglionectomy decreased significantly estradiol and testosterone uptake by the pineal gland as well as high affinity binding to pineal cytoplasmic and nuclear components. Norepinephrine treatment counteracted all the effects of ganglionectomy but was unable to modify hormone uptake and binding by the pineal gland of sham-operated controls. Pre-treatment with actinomycin D or propranolol but not with phentolamine impaired norepinephrine effects; propranolol blockage however was only partial. Administration of isoproterenol, L-dopa or phentolamine increased hormone uptake by denervated pineals. The effects of isoproterenol were also observed and were blocked by propranolol. These results indicate that sex steroid receptors in the pinealocytes are controlled by norepinephrine via beta-adrenergic receptors and that depletion of neural norepinephrine enhanced responsiveness of pineal hormone receptors to exogenous catecholamines. 相似文献
3.
Proteome analysis of combined effects of androgen and estrogen on the mouse mammary gland 总被引:6,自引:0,他引:6
We and other investigators have previously shown that estrogen and androgen have synergistic effects on the growth of mammary epithelial ducts and alveoli in the Noble mouse. However, the molecular mechanisms behind the synergy are unknown. In the present study, we treated female FVB mice with 17-estrodial (E2) and 5-dihydrotestosterone-bezonate (DHT-B) using slow-releasing hormone pellets for 7 months. Dissection showed that hormone treatment caused atypical hyperplasia of mammary ducts and alveoli. A functional proteomic approach was used to study the holistic protein changes in mammary glands. 2-DE was used to separate proteins. Twenty-five protein spots that were differentially expressed in hormone-treated tissues compared to the control were identified by MALDI-TOF-MS, and ESI-quadrupole-TOF-MS, which include some proteins that are correlative with response to estrogen and androgen stimulation, cells differentiation and growth, signal transduction, metabolism, etc. Real-time RT-PCR was carried out to verify the different expression. These results offered some clues to understand the function of E2 and DHT-B. 相似文献
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To explore the expression of androgen receptor (AR) and estrogen receptor alpha (ERα) in the developing pituitary of male lamb, we detected AR and ERα expression in the anterior pituitary of lambs aged 2-7 months old by immunohistochemistry. The results showed that both AR immunoreactivity (AR-ir) and ERα immunoreactivity (ERα-ir) were localized in the nuclei of anterior pituitary cell. The percentage of the anterior pituitary cells expressing ERα fluctuated from 8.79±0.02% to 11.80±0.04% during the examined stages, but fell significantly to the lowest level at 6 months. While the proportion of AR-ir showed significant changes, it was in 11.52±1.26% at 2 months, it firstly increased to 19.86±1.03% at 3 months, and then significantly decreased to 8.18±1.17% at 6 months (P<0.05). The expression of both AR-ir and ERα-ir were the lowest level at 6 months old. By staining for PCNA, we observed that the changes in expression of AR and ERα at different lamb ages did not result from cell proliferation of anterior pituitary cells. These results indicate that both AR and ERα are important in regulation of secretary function of anterior pituitary in sheep lamb, although the related mechanism needs to be elucidated further. 相似文献
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Perinatal exposure to the synthetic estrogen, diethylstilbestrol (DES), affects the structure of both male and female reproductive systems. Changes may also occur in the levels of steroid hormone receptors. Cytosolic and nuclear androgen and estrogen receptor levels (expressed per mg DNA) from the sex accessory glands of male BALB/c mice exposed neonatally to DES were analyzed by exchange assays. Neonatal DES exposure caused significant decreases in: (1) cytosolic androgen and cytosolic and nuclear estrogen receptor levels in the anterior prostate and (2) cytosolic estrogen receptor levels in the ventral prostate. A significant increase was seen in the cytosolic estrogen receptor levels in the seminal vesicle. Significant decreases in cytosolic protein levels occurred in all DES-exposed glands. 相似文献
8.
Expression of androgen receptor and its co-localization with estrogen receptor-alpha in the developing pituitary gland of sheep fetus 总被引:3,自引:3,他引:0
No information is known concerning the expression of androgen receptor (AR) and its co-localization with estrogen receptor
alpha (ERα) in the developing pituitary of sheep fetus. In the present study, we detected AR expression and its co-localization
with ERα in the anterior pituitary of sheep fetus from day 60 of gestation to the postnatal by dual immunochemistry. The results
showed that both AR immunoreactivity (AR-ir) and ERα immunoreactivity (ERα-ir) were predominantly localized in the nuclei
of LH positive gonadotropes. The cell counting results showed that the percentage of the anterior pituitary cells expressing
AR fluctuated from 13.51 ± 0.92 to 17.05 ± 1.83% during the examined stages, but there were no significant differences between
sexes and among ages examined (P > 0.05). However, the proportion of AR-ir cells containing LH markedly increased from day 60 of gestation to the neonatal
(P < 0.05). The percentage of AR-ir cells expressing ERα-ir significantly increased from day 60 of gestation to the neonatal,
respectively (P < 0.05), but no significant differences were seen between genders at each stage examined. These results indicate that both
AR and ERα are mainly expressed in the gonadotropes of anterior pituitary gland of sheep fetuses, whereas the functions and
interaction of AR and ERα expressions in the developing pituitary gland are required to be elucidated further.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
9.
Androgen metabolism in target tissues constitutes an important step for understanding hormone action. The in situ aromatization of androgen represents one of these metabolic events. We characterized aromatase activity (AA) in a microsomal preparation of brain tissue from adult guinea pigs since earlier reports questioned its presence in neural tissues of this species. Analyses revealed an apparent substrate affinity (approximately 17 nM) that was equivalent in adult males and females. However, adult male brains contained greater quantities of AA than female brains. Specifically, AA in the preoptic area (POA: p less than 0.05) and the medial basal hypothalamus (MBH; p less than 0.01) was greater in males than in females. AA was concentrated in the limbic system and hypothalamus (amygdala greater than POA greater than septum greater than MBH), whereas low levels were consistently measured in cortical tissue. In vitro estrogen formation was significantly lower in POA (p less than 0.05) and MBH (p less than 0.01) after castration. After dihydrotestosterone treatment, AA returned to levels equal to or greater than those observed in intact males. These data indicate that AA does exist in the guinea pig brain and is modulated by androgens through the androgen receptor. The presence of high levels of aromatase activity may suggest a role for locally formed estrogens in brain function in this species. 相似文献
10.
The aim of this study was to determine in the ring dove, the effects of aromatase inhibition on the expression of aggressive courtship and nest-soliciting behaviours in relation to the distribution of cells containing immunoreactive androgen (AR) and progesterone (PR) receptor in the hypothalamus and pituitary gland. Isolated sexually experienced ring doves were transferred in opposite sex pairs to individual breeding cages, and then injected with the aromatase inhibitor, fadrozole (four males and four females), or saline vehicle (four males and four females) for 3 days at 12 hourly intervals. Saline-injected control males displayed aggressive courtship behaviours (bow-cooing and hop-charging) and nest-soliciting throughout the study, and control females displayed nest-soliciting. By day 3, fadrozole treatment resulted in the disappearance of all these behaviours and in a decrease or disappearance of AR and PR in the anterior pituitary gland, and in the nucleus preopticus paraventricularis magnocellularis (PPM), nucleus preopticus medialis (POM), nucleus hypothalami lateralis posterioris (PLH), and ventral, lateral and dorsal nucleus tuberalis in the hypothalamus (VTu, LTu, DTu). In the nucleus preopticus anterior (POA), fadrozole treatment decreased AR in both sexes and decreased PR in females but not in males. Cells containing co-localized nuclear AR and PR were found in all hypothalamic areas examined, and in the anterior pituitary gland. Fadrozole is suggested to reduce the local availability of estrogen required indirectly for the induction of AR, and except in cells containing PR in the male POA, for the direct induction of PR. It is suggested that aggressive courtship behaviour is terminated by “cross talk” between aromatase-independent PR and aromatase-dependent AR co-localized in neurons in the POA. Aromatase-independent PR may increase in the male POA in response to visual cues provided by a partner. Aromatase-dependent PR in the POM, and basal hypothalamus may play a role in the facilitatory effect of progesterone on estrogen-induced nest-orientated behaviours. (Mol Cell Biochem 276: 193–204, 2005) 相似文献
11.
Larionov AA Poroshina TE Zimarina TS Leenman EE Bershteĭn LM 《Rossi?skii fiziologicheski? zhurnal imeni I.M. Sechenova / Rossi?skaia akademiia nauk》2000,86(1):10-17
Extragonadal aromatization plays an important role in many physiological and pathological conditions. It has been found that incubation of the peripheral blood mononuclears in the RPMI-1640 medium with 10% fetal calf serum during 48 hrs is able to induce the aromatase gene expression. The latter did not occur in 11 samples of mononuclears of the intra-tissue leukocyte infiltration which finding needs further investigation. The data obtained suggest that the possibility of the aromatase gene induction in leukocytes is associated with the cellular fraction capable of the substrate adhesion. 相似文献
12.
Dr. J. J. Peluso J. Charlesworth C. England-Charlesworth 《Cell and tissue research》1981,216(3):615-624
Summary The effects of Nitromifene citrate (CI 628), an antiestrogen, and Flutamide, an antiandrogen, on the ultrastructure and viability of the preovulatory follicle and granulosa cells were examined both in vivo and in vitro. In vivo administration of either antihormone induced degeneration within the granulosa cells. In some of the affected granulosa cells, the nuclear material was condensed while the cytoplasm and associated organelles were unaltered. In others, the density of the cytoplasm was reduced, the smooth endoplasmic reticulum was dilated but the nucleus remained unaltered. In vitro, either antihormone reduced granulosa-cell viability but the granulosa cells were twenty times more sensitive to CI 628 than to Flutamide. In addition, exposure to CI 628 induced nuclear condensation without affecting the cytoplasm, while Flutamide induced the deterioration of the cytoplasm without altering the nucleus. These observations suggest that: (1) both estrogen and androgens control the viability of the granulosa cells and thereby the follicle, (2) the action of estrogen and androgen is mediated through receptors within the granulosa cells since these antihormones prevent the nuclear uptake of their respective hormone, (3) the granulosa cells of preovulatory follicles appear to be more dependent on estrogen than on androgen, and (4) each steroid appears to have a specific role in maintaining the granulosa cell; estrogens control the integrity of the nucleus while androgens preserve the cytoplasmic organization of the granulosa cell.The authors are indebted to Dr. Neri of Schering AG for donating the Flutamide and to Dr. Westland of Warner-Lambert/Parke-Davis for providing CI-628 相似文献
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Identification of genetic pathways activated by the androgen receptor during the induction of proliferation in the ventral prostate gland 总被引:4,自引:0,他引:4
Nantermet PV Xu J Yu Y Hodor P Holder D Adamski S Gentile MA Kimmel DB Harada S Gerhold D Freedman LP Ray WJ 《The Journal of biological chemistry》2004,279(2):1310-1322
15.
Reducing endogenous estrogen leads to increased proliferation of porcine Sertoli cells during the first 2 months of life. The resulting increase in porcine Sertoli cell numbers is maintained through puberty. The reduced estrogen appears to be the direct hormonal mediator because essentially no changes are observed in other hormones. However, the mechanism for this effect on Sertoli cell proliferation is unknown. The objective of these studies was to evaluate estrogen receptors alpha and beta (ESR1 and ESR2) in conjunction with androgen receptor (AR) on Sertoli cells and other testicular cell types, as an initial step toward understanding how reduced estrogen leads to increased Sertoli cell numbers. Testis sections from treated animals (aromatase inhibition to decrease endogenous estrogen beginning at 1 week of age) and from littermate controls treated with vehicle were subjected to immunocytochemical labeling for ESR1, ESR2, and AR. Three observers scored Sertoli cells, interstitial cells, peritubular myoid cells, and germ cells for intensity of labeling (0: absent; 1+: weak; 2+: moderate; or 3+: strong labeling). AR in Sertoli cells was readily detected at 1 week of age, was very faint in 2-month vehicle controls, and labeling appeared to increase in 3-month vehicle controls. AR in Sertoli cells, interstitial cells, and apparently germ cells was increased in treated animals at 2 months of age compared with the vehicle controls. This increase was confirmed in western blots. ESR1 and ESR 2 were clearly present in Sertoli cells from 1-week-old animals; ESR in Sertoli cells generally decreased with age with the decrease more apparent for ESR2. ESR1 in Sertoli cells and peritubular myoid cells exhibited some treatment-related effects but reduction of endogenous estrogen did not appear to affect ESR2 in the boar testis. The observed alterations in AR and ESR1 may mediate the increases in Sertoli cell proliferation following inhibition of endogenous estrogen production or may reflect the altered function of the Sertoli cells and peritubular myoid cells. 相似文献
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Alexander Abazid Benedikt Martin Anja Choinowski Rhiannon V. McNeill Lars-Ove Brandenburg Patrick Ziegler Uwe Zimmermann Martin Burchardt Holger Erb Matthias B. Stope 《Journal of cellular biochemistry》2019,120(10):16711-16722
Enzalutamide's accepted mode of action is by targeting the androgen receptor's (AR) activity. In clinical practice, enzalutamide demonstrates a good benefit-risk profile for the treatment of advanced prostate cancer (PC), even after poor response to standard antihormonal treatment. However, since both, well-established antiandrogens and enzalutamide, target AR functionality, we hypothesized that additional unknown mechanisms might be responsible for enzalutamide's superior anticancer activity. In the current study, PC cells were incubated with enzalutamide and enzalutamide-dependent modulation of apoptotic mechanisms were assessed via Western blot analysis, TDT-mediated dUTP-biotin nick end-labeling assay, and nuclear morphology assay. Alterations of heat shock protein (HSP), AR, and estrogen receptor (ER) expression were examined by Western blot analysis. Enzalutamide attenuated the proliferation of PC cells in a time- and dose-dependent manner. In the presence of enzalutamide, apoptosis occurred which was shown by increased BAX expression, decreased Bcl-2 expression, nuclear pyknosis, and genomic DNA fragmentation. Moreover, enzalutamide inhibited the expression of HSPs primarily involved in steroid receptor stabilization and suppressed AR and ERβ1 expression. This study demonstrates for the first time that enzalutamide treatment of PC cells triggers varying molecular mechanisms resulting in antiproliferative effects of the drug. In addition to the well-characterized antagonistic inhibition of AR functionality, we have shown that enzalutamide also affects the intracellular synthesis of steroid receptor-associated HSPs, thereby diminishing the expression of AR and ERβ1 proteins and inducing apoptotic pathways. According to an indirect attenuation of HSP-associated factors such as steroid receptors, endometrial carcinoma, uterine leiomyosarcoma, and mamma carcinoma cells also demonstrated inhibited cell growth in the presence of enzalutamide. Our data, therefore, suggest that enzalutamide's high efficacy is at least partially independent of AR and p53 protein expression, which are frequently lost in advanced PC. 相似文献
18.
Genes regulating gland development in the cotton plant 总被引:1,自引:0,他引:1
Madhusudhana R. Janga Devendra Pandeya LeAnne M. Campbell Kranti Konganti Stephany Toinga Villafuerte Lorraine Puckhaber Alan Pepper Robert D. Stipanovic Jodi A. Scheffler Keerti S. Rathore 《Plant biotechnology journal》2019,17(6):1142-1153
19.
Aromatase cytochrome P450 and estrogen and progesterone receptors in uterine sarcomas: correlation with clinical parameters 总被引:3,自引:0,他引:3
Kitaoka Y Kitawaki J Koshiba H Inoue S Ishihara H Teramoto M Honjo H 《The Journal of steroid biochemistry and molecular biology》2004,88(2):183-189
We examined the immunohistochemical expression of aromatase cytochrome P450 (P450arom), estrogen receptor (ER), progesterone receptor (PR), and Ki-67 in postoperative uterine sarcomas (n = 31) and the corresponding eutopic endometria (n = 20) to evaluate the relationships between the endocrine character of uterine sarcomas and the clinical features. In sarcoma tissues, P450arom was detected in 55% of cases, ER in 42%, PR in 42%, and Ki-67 in 90%. In eutopic endometria, P450arom was detected in 60% of cases, ER in 60%, and PR in 35%. There were correlations in the steroid-related proteins between the tumors and endometria (P = 0.001-0.026). The positivity of endometrial P450arom (P = 0.04) and ER (P = 0.006) was higher in surviving patients than dead patients regardless of the menstrual state. The results demonstrate correlation between the expression of P450arom, ER, and PR in tumors and eutopic endometria. Intense expression of the steroid-related proteins was associated with better survival. 相似文献
20.
G S Prins 《Journal of steroid biochemistry》1989,33(3):319-326
In order to understand the hormonal regulation of androgen receptors (AR) in the separate lobes of the rat prostate gland, the present study examined AR levels in the ventral, dorsal and lateral prostate lobes as a function of androgen withdrawal to complete prostatic regression and subsequent testosterone replacement. In the intact rat, the 3 prostate lobes contained significantly different amounts of androgen binding sites. Mean number of total cellular AR in the ventral, dorsal and lateral lobes was 7370, 1690, and 1015 fm/mg DNA, respectively. These receptors were primarily localized within the nuclear fraction of homogenized tissue: ventral, 86%; dorsal, 83%; and lateral, 100% nuclear localization. Androgen withdrawal was initiated via castration and rats were sacrificed 1, 2, 3, 5, 7, 10 and 14 days thereafter. Nuclear AR levels fell rapidly to 5, 24 and 30% of intact values by 48 h in the ventral, dorsal and lateral lobes, respectively. Levels of nuclear AR continued to decline in the ventral and dorsal lobes to undetectable levels by Day 10. In marked contrast, lateral lobe nuclear AR began to increase on Day 3 postcastration, reaching intact values by Day 7 and 133% intact levels by Day 14. Cytosolic AR in the ventral and dorsal lobes initially increased following castration, but subsequently declined to low levels by Day 14. Cytosolic AR were not detectable in the lateral prostate at any time point following castration. To determine the nuclear AR response to testosterone at this time, 14 day castrate rats were given 2 cm testosterone implants and sacrificed 1, 3, 5, 7, 10 and 14 days thereafter. As expected, nuclear AR rapidly returned in the ventral and dorsal lobes by Day 1 and reached a plateau by Day 5. A short term response to androgen exposure occurred in the lateral lobe where an immediate 9-fold increase in nuclear AR quantity was observed; however, these levels rapidly declined to pre-implant values by Day 5 and remained at that level despite continued exposure to testosterone. These f findings indicate that while nuclear AR levels in the ventral and dorsal prostate are primarily regulated by androgens, a testosterone-independent component exists within the lateral lobe. 相似文献