Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of "soft" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, "scirrhous" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.
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PMID:Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer. 16 44

Estradiol produces both hypertrophic and hyperplastic changes in the uterus, and these changes are associated with alterations in the structure of collagen in the lamina propria. Estriol induces only hypertrophic responses in the immature rat uterus; its effects on collagen structure were characterized in this study. Light micrographs of Masson's trichrome-stained sections revealed that the intensity of the collagen stain in the lamina propria of the rat uterus was profoundly reduced, relative to that in controls, 4 h after estriol (40 micrograms/kg) administration. These changes were not evident 24 h after estriol administration. In control uteri, transmission electron micrographs revealed that the collagen fibers surrounding stromal cells formed dense collections of bundles that were seen throughout the extracellular matrix, whereas in tissues exposed to estriol 4 h earlier, large regions of the extracellular spaces were devoid of collagen bundles. The 4-h changes in collagen were eliminated when animals were pretreated with actinomycin D (8 mg/kg) or cycloheximide (4 mg/kg). Dense collections of collagen bundles were present in tissues 24 h after estriol treatment, and their appearance was not altered by actinomycin D or cycloheximide treatment. Alterations in collagen 4 h after hormone administration appeared to be estrogen-specific since dexamethasone (600 micrograms/kg) and dihydrotestosterone (400 micrograms/kg) had no effect. These data provide evidence that the changes in collagen structure in the uterus are associated with events that function during the hypertrophic growth responses induced by estrogens.
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PMID:Effect of estriol on the structure and organization of collagen in the lamina propria of the immature rat uterus. 163 52

We recently reported that estrogen exerts distinct effects on the GH/IGF-1 axis that are dependent on the route of delivery, probably reflecting a first-pass effect on hepatic IGF-1 production. Oral administration reduces IGF-1 and increases GH levels; transdermal administration elevates IGF-1 without changing GH concentrations. Since mesenchymal tissue is a target for GH and IGF-1 action, we studied changes in the GH/IGF-1 axis following oral (ethinyl estradiol, 20 micrograms/day) versus transdermal (Estraderm 100 TTS, Ciba Geigy, 100 micrograms 17 beta-estradiol per day) estrogen delivery and compared corresponding effects on connective and bone tissue metabolism. Mean 24 h GH levels, IGF-1, markers of fibroblast (procollagen III) and osteoblast (procollagen I, osteocalcin) function, and indices of bone turnover (fasting urinary hydroxyproline and calcium to creatinine ratios, UOHPr/Cr and UCa/Cr) were measured before and after 2 months of either oral or transdermal therapy in two groups of postmenopausal women. Transdermal estrogen administration significantly (p less than 0.05) increased IGF-1, procollagen III, procollagen I, osteocalcin, and UOHPr/Cr. In contrast, oral estrogen administration had a suppressive effect; the levels of IGF-1 (p = 0.001), procollagen III (p = 0.018), procollagen I (p = 0.002), osteocalcin (p = 0.015), and UOHPr/Cr (p = 0.004) were significantly different from those measured during transdermal administration. Both treatments significantly reduced UCa/Cr (p less than 0.015). IGF-1 changes during estrogen therapy were significantly related (p less than 0.05) to changes in procollagen III, procollagen I, osteocalcin, and UOHPr/Cr. Transdermally delivered estrogen stimulates IGF-1 production, increases osteoblastic function, and stimulates bone and nonbone collagen synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impact of short-term estrogen administration on growth hormone secretion and action: distinct route-dependent effects on connective and bone tissue metabolism. 164 49

Although it is widely accepted that estrogens exert a major trophic effect on follicular growth, their mechanism of action has not been established. We examined the effect of estrogen treatment in vivo or in vitro on DNA synthesis in rat granulosa cells cultured under defined conditions (DMEM:F12, collagen-coated plastic wells). Treatment with diethylstilbestrol (DES) in vivo (silastic implants containing 5 mg DES) for at least 2 days was required to observe a significant stimulation of 3H-thymidine incorporation by insulin (1 microgram/ml) in culture. Rat thecal/interstitial cells (TI) were isolated from DES-treated rats and cultured under the same conditions as granulosa cells. Conditioned media from TI cells stimulated DNA synthesis in granulosa cell cultures (as much as twofold). This effect was markedly amplified by estradiol treatment (1 microgram/ml) of the TI cell cultures. Addition of estradiol to granulosa cell cultures enhanced the effect of conditioned medium from nontreated TI cells. Conditioned medium from estradiol-treated TI cells stimulated DNA synthesis in granulosa cells from both DES-treated and nontreated rats. Estradiol had no effect when added directly to purified granulosa cell cultures but stimulated 3H-thymidine incorporation in crude preparations of ovarian cells. The stimulatory effects of TI cell-conditioned medium and insulin were reflected in the final cell densities achieved after 9 days in culture. We conclude that the mitogenic actions of estrogens in the ovary involve sensitization of granulosa cells to locally present mitogens like insulin and a TI cell-derived growth factor.
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PMID:Hormonal regulation of rat granulosa cell deoxyribonucleic acid synthesis: effects of estrogens. 186 46

Health practitioners use many methods and agents to bring on cervical ripening in early pregnancy, such as intracervical tents and pharmacological techniques, to induce a therapeutic abortion. Prostaglandins alter myometrial and cervical tissue and are the most often used pharmacological technique. Reduced collagen concentration, an increase in water volume, an increase in prostaglandins (PGE2, PGI2, and PGF2 alpha), and a change in the glycosaminoglycan (GAG) content coincide with cervical ripening, yet the mechanism responsible for these changes is obscure. Prostaglandins appear to cause the breakdown of collagen or change the GAG/proteoglycan content. Research shows that prostaglandins can initiate cervical ripening at any stage of pregnancy. Estradiol stimulates prostaglandin production thereby al so inducing cervical dilation. Relaxin also demonstrates an ability to ripen the cervix. In addition, mifepristone (RU-486) is gaining acceptance as a cervical ripening agent. In fact, RU-486 and gemeprost have at least 95% success rate compared to 92% for gemeprost alone or 85% with RU-486 alone. The only effective and acceptable prostaglandins to use at gestation of 0-8 weeks are sulprostone, gemeprost, and 9-methylene-PGE2. At t his gestational age, pharmacological modulation is all that is needed. Even though they are effective (abortion rate 90%), side effects are expected to occur (pain, nausea, and vomiting). Similarly, prostaglandin analogues are preferable for cervical ripening in women at 8-12 weeks gestation. Suction curettage or other surgical techniques then are used to remove the conceptus. At 12-16 weeks gestation, many physicians prefer the same protocol as that of 8-12 weeks gestation. Other choose to infuse PGE2 and saline into the amniotic fluid to stimulate uterine contractions. Another procedure at 12-16 weeks involves 1mg vaginal pessaries of gemeprost every 3 hours to ripen the cervix and stimulate contractions. After 16 weeks, the methods for 12-16 weeks still apply.
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PMID:Pharmacological modulation of cervical compliance in the first and second trimesters of pregnancy. 187 72

Prolactin is now accepted as a normal product of the decidual cells of the human endometrium. We investigated the effect of epidermal growth factor (EGF) with estradiol and progesterone on prolactin secretion by the decidual tissues from the early pregnant endometrium. The decidual tissues were separated from villi, minced and cultured in collagen gel matrix with serum-free medium. Immunological staining of the cultured decidual tissues showed prolactin localization and EGF receptors on the stromal cells. Cultured media were collected every 2 days. The culture for the first 2 days was incubated with the serum-free medium alone (= preculture), and the following test culture was supplemented with/without additives. The prolactin content in cultured media was quantified by EIA. The results of the effect of steroid(s) and EGF were represented as a comparison of prolactin contents in the preculture and the test culture. An increase in prolactin secretion was found after the tissues were treated with a combination of 10(-8)M estradiol and 10(-6)M progesterone or 10(-6)M progesterone alone. After 8 days, the prolactin secretion rate increased about 3-fold over the precultured value. Estradiol alone kept the prolactin secretion at the precultured value. Prolactin secretion gradually decreased in the non-additive culture. These results indicate that progesterone was essential in the secretion of prolactin. Simultaneously, similar decidual tissues were incubated with a combination of EGF and steroid(s). The secretion of prolactin in the group treated with progesterone alone decreased dose-dependently responding to added EGF on the 8th day of culture. In the presence of estradiol and progesterone, the secretion rate decreased to the values similar to the progesterone alone group with the addition of 0.1, 1 ng/ml EGF, and the decrease in prolactin secretion was less with the addition of 10 ng/ml EGF. Mixed cultures of the decidual tissues and villi showed that the prolactin secretion rate increased in all groups treated with/without estradiol and/or progesterone. These results imply that progesterone derived from villi might control decidual prolactin secretion. The effect of high concentration EGF (50 ng/ml) on the prolactin secretion appeared similar to the isolated decidual tissues. These results suggest that decidual prolactin secretion is regulated by the combined effects of steroids and EGF.
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PMID:[The effect of epidermal growth factor (EGF) with estradiol and progesterone on prolactin secretion from cultured human decidual tissues of early pregnancy]. 220 24

Cervical ripening is reviewed from the viewpoint of mechanical properties, histological and biochemical structure of cervical tissue, and the role of hormones and other bioactive agents in the process. The uterine cervix begins abruptly with a 2-3 mm transition from the myometrium and is made of 80% type I collagen and 20% type III collagen fibers covalently cross linked, and glycosaminoglyucans covalently bound to protein cores. During pregnancy the collagen concentration is halved and its extractability increases due to changes in the proteoglycan composition, an increase in acidic relative to neutral proteins. These changes are responsible for the softening of the cervix (Goodell's sign) and the isthmus (Hegar's sign). Histologically the collagen fibers appear thinner and more spread out. Polymorphonuclear leukocytes and eosinophils may be involved in the softening process. Factors theorized or know to be involved in cervical ripening are progesterone, estradiol, prostaglandins (PGs), relaxin, and cytokines. Progesterone withdrawal has been shown in animal models. Estradiol either induces PG synthesis or sensitizes the cervix to locally produced PGs. PGE2 and PGF2alpha receptors have been found in cervical plasma membranes, have been isolated from tissue, their local synthesis can be manipulated, and their clinical use is well documented. Relaxin is a peptide synthesized in the corpus luteum, uterus and placenta, and is known to relax the pelvic girdle, restrain myometrial activity and soften the cervix. Cytokines such as interleukin-1 and tumor necrosis factor are being studies because of their ability to stimulate collagenase.
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PMID:The physiology of cervical ripening and cervical dilatation and the effect of abortifacient drugs. 222 99

Thecal cells isolated from bovine ovarian follicles were cultured with a serum-free basal medium or a serum-free complete medium in the presence or absence of collagen gel matrix, and their cellular proliferation and steroidogenesis were compared with those of cells cultured with a serum-containing medium. The cells cultured with the serum-free basal medium produced larger amounts of progesterone, androstenedione, and estradiol than the cells cultured with the serum-containing medium, but no appreciable cell proliferation was observed in the serum-free medium. Response of thecal cells to 8 bromo-cAMP, a steroidogenic agent, varied according to the type of steroid production examined and the type of culture medium used. In a cultivation period of 4 d, progesterone production was stimulated about five-fold by 8 bromo-cAMP in the serum-free complete medium on collagen gel matrix and in the serum-free basal medium without collagen matrix, whereas androstenedione production was stimulated about three- to fourfold in the serum-free complete medium on collagen gel matrix and in the serum-free basal medium with or without collagen matrix. Estradiol production, however, was significantly suppressed by 8 bromo-cAMP in the serum-free complete medium on collagen gel matrix and also in the serum-containing medium. Thus, among the conditions examined, the most suitable primary culture media for steroidogenesis of thecal cells were the serum-free media, especially serum-free complete medium on collagen gel matrix.
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PMID:Serum-free medium conditions for steroidogenesis of bovine follicular thecal cells cultured on collagen gel matrix. 231 3

Estradiol (E2) replacement therapy effectively prevents or delays postmenopausal bone loss, but the mode of E2 action on bone is still unknown. Recently, the presence of E2 receptors was described for bone-derived cells. In this study we examined the estrogen responsiveness of osteoblastic cells using the experimentally immortalized calvarial cell lines RCT-1 and RCT-3 as well as primary cultures of calvarial and trabecular bone cells. E2 treatment reduced PTH-stimulated adenylate cyclase activity by 20-30% in RCT cells; the maximum effect was observed after treatment with 1 nM E2 for 4 h or longer. In trabecular cells E2 decreased PTH-stimulated adenylate cyclase activity by 60-80%. After a lag period of at least 48 h, E2 treatment (0.01-10 nM) increased cell number and [3H]thymidine incorporation in both RCT-3 cells and primary cultures of trabecular cells to 20-60% above control values. Half-maximal effects were observed at about 1 nM E2. Antibodies against insulin-like growth factor-I (IGF-I) inhibited the E2-induced proliferation in a dose-dependent manner without affecting basal growth. Furthermore, E2 treatment increased the steady state levels of IGF-I mRNA 2- to 2.5-fold in calvarial and RCT-3 cells compared to control levels. In addition, E2 (10 nM) increased the level of collagen mRNA more than 2-fold and opposed the suppression of collagen mRNA produced by PTH treatment. The E2 effects were specific to 17 beta-E2, since they were not observed with the biologically less active stereoisomer 17 alpha-E2 and were blocked by the E2 antagonist tamoxifen (1 microM). Thus, for osteoblastic cells in culture, E2 can directly stimulate proliferation as well as collagen and IGF-I mRNA while decreasing PTH responsiveness; these effects could explain the anabolic and anticatabolic effects of E2 on bone.
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PMID:Estradiol effects on proliferation, messenger ribonucleic acid for collagen and insulin-like growth factor-I, and parathyroid hormone-stimulated adenylate cyclase activity in osteoblastic cells from calvariae and long bones. 275 78

The normal and the pathologically changed human myometrium was cultured in the diffusion chamber implanted in the subcutaneous cellular tissue of the rat. In the absence of hormonal influence the growth of myometrium culture is only insignificant, while no myoma cell growth was found at all. Estradiol stimulates the growth and development of the myometrium culture and the myoma. A combined action of estradiol and progesterone stimulates the collagen formation.
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PMID:[Hormone-dependent characteristics of the myocyte cell surface in the human myoma and myometrium cultured in diffusion chambers]. 328 73


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