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1.
In female mice (n = 240), the estradiol stimulus was characterized by studying preexposure effects of sex steroids and sickness-inducing drugs on estradiol-induced (50 micrograms/kg SC) conditioned taste aversion (CTA). It was established that preexposure to estradiol itself (2-50 micrograms/kg SC) attenuates the development of CTA produced by the hormone. Only partial crossfamiliarization effects were found with progesterone (50-200 micrograms/kg SC) and testosterone (250-1000 micrograms/kg SC), steroids that induce CTA themselves. Preexposure to the sickness-inducing drugs lithium chloride (22 mg/kg SC) and apomorphine (0.1-0.2 mg/kg SC) prevented or substantially reduced the development of estradiol-induced CTA, respectively. It was concluded that only a low degree of stimulus resemblance exists between estradiol and the other principal sex steroids, progesterone and testosterone. In addition, it was concluded that the estradiol stimulus resembles the stimuli produced by sickness-inducing drugs. 相似文献
2.
AE Lemus R Jaimez C Lemini M Menjivar G Silva C Rubio-Poo F Valenzuela F Larrea 《Canadian Metallurgical Quarterly》1998,63(7-8):433-438
In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen derivative, upon coagulation, serum LH, pituitary progestin receptors, uterine weight, and endometrium morphological changes in the castrated female rat. Groups of animals were subcutaneously (s.c.) injected with either estradiol (E2) (0.1 up to 1000 micrograms/animal), pentolame (1 up to 1000 micrograms/animal), or the vehicle alone daily for 5 consecutive days starting 2 weeks following ovariectomy. Administration of pentolame (10 to 1000 micrograms/animal) increased significantly (p < 0.05) the blood clotting time when compared with that obtained in the group of control animals (EC50 582 micrograms). Pentolame (500 and 1000 micrograms/rat for 5 days) caused a significant inhibition (p < 0.01) of serum LH levels (IC50 860 micrograms), which remained suppressed until Day 5 post last injection. In addition, treatment with pentolame was able to restore in the castrated female rat the presence of specific estrogen-dependent progestin binding sites at the anterior pituitary level. The affinity constants and the number of binding sites of pentolame-induced progestin receptors were similar to those obtained with estradiol at equipotent doses (860 micrograms vs. 1 microgram/animal, respectively). Administration of the 17 beta-aminoestrogen derivative resulted in a significant increase in uterine weight (EC50 420 micrograms) and endometrial characteristics were indistinguishable from those observed in the group of rats treated with E2. 相似文献
3.
M Kauppila J Viikari K Irjala P Koskinen K Remes 《Canadian Metallurgical Quarterly》1998,244(5):411-416
In this study including 26 patients with dyslipoproteinemia classified IIa, we evaluated biochemical and clinical safety of Nomegestrol acetate (Lutenyl) used for its antigonadotrophin property. It was administered alone, during 3 cycles at the dose of 5 mg/d for 21 days by cycle and then it was associated (at the same sequence and dose), without any wash out, for the next 6 cycles, with a 17 beta estradiol patch (Estraderm TTS 50), 50 micrograms/d from the 11th to the 21st day of each cycle. Nomegestrol acetate, alone, had no significant effect on glycemia, antithrombin III, triglycerides, total cholesterol, apoprotein A1, and LpA1 values compared to those at baseline but apoprotein B and Lp (a) values tended to decrease slightly. Serum progesterone levels were collapsed, and FSH values were low. Weight and blood pressure remained constant. Adding 17 beta estradiol enabled to significantly decrease and normalize the apoprotein B values after the first 3 cycles compared to the baseline values, then these values remained constant during the next 3 cycles. There was no effect on the other parameters (except for a significant increase in plasmatic estradiol values) on the antigonadotrophin property of Nomegestrol acetate, nor on weight and blood pressure which remained constant. Moreover, we observed an important decrease in the rate of amenorrheic cycles compared to those with Nomegestrol acetate alone. 相似文献
4.
This study evaluated the expression of the corticosteroid-metabolizing enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) during in vitro decidualization of human endometrial stromal cells. The cultured stromal cells displayed both NADP(+)-dependent (type 1) and NAD(+)-dependent (type 2) 11 beta HSD activities under basal conditions. Although the cells did not respond to estradiol (E2) added alone, catalytic levels of both isoforms were enhanced by medroxyprogesterone acetate (MPA) and further enhanced by E2 plus MPA. Type I messenger RNA (mRNA) was undetected by Northern analysis of total RNA, but was evident as a 1.5-kilobase band in polyadenylated selected RNA from E2- plus MPA-treated cultures. Use of RT-PCR to augment the sensitivity of mRNA detection revealed the presence of type I mRNA as a faint band in the MPA-treated cultures and as an intense band in the E2- plus MPA-treated cultures. Thus, type I mRNA is present as a low abundance message in the cultured stromal cells whose steady state levels parallel progestin-enhanced enzyme activity. As the expression of several progestin-regulated decidualization markers is also augmented by E2, the results of the present study reveal a correlation between enhanced 11 beta HSD expression and the decidualization reaction. Time-course measurements indicated that elevated 11 beta HSD expression is an early event in the decidualization response, which precedes E2- plus MPA-enhanced PRL production by several days. Clear dose-response effects on both type 1 and type 2 11 beta HSD activities were obtained in cells incubated with 10(-8) mol/liter E2 added together with MPA at concentrations that approximated circulating progesterone levels from the luteal phase (10(-9) mol/liter) through pregnancy (10(-7) mol/liter). Corticosteroids are thought to exert toxic and teratogenic effects on the implanting embryo and could influence trophoblast invasion by regulating extracellular matrix turnover. Therefore, the novel finding that decidualization involves marked enhancement of the corticosteroid-metabolizing capacity of stromal cells suggests a mechanism by which decidual cells could affect the health and invasiveness of implanting trophoblastic cells. 相似文献
5.
G Menozzi 《Canadian Metallurgical Quarterly》1998,50(5):213-215
BACKGROUND: The influence of hormone replacement therapy on the body weight has been studied. METHODS: For this purpose, a group of 205 women in spontaneous menopause, were selected at the Menopause Centre in Suzzara: they were given a continuative replacement therapy for a period of 12 months (estradiol 50/60 micrograms and medroxyprogesterone acetate, 5/10 micrograms twelve days a month). RESULTS: After twelve months, 30% of the 200 patients who completed the study, showed a weight increase which was significant only in 20%, with no variation of the Body Mass Index. CONCLUSIONS: From the data obtained, two remarks can be done: the HRT contributes in an insignificant way to the body weight and probably these results must also be ascribed to the choice of neutral progestinics which do not possess androgenical mineralcorticoid effects. 相似文献
6.
OBJECTIVE: To establish the efficacy and acceptability of combined continuous low-dose oestrogen and low-dose progestogen therapy, to determine whether any of three commercially available progestogens had any advantages or disadvantages in these circumstances and whether use of the lowest clinically effective oestrogen dose affected other outcomes being measured. DESIGN: A 12-month, prospective, open label, single centre, randomised trial. PATIENTS AND METHODS: Seventy-five postmenopausal women already receiving hormone replacement therapy in the form of conjugated equine oestrogens (CEE) (0.625 mg daily) and cyclical medroxyprogesterone acetate (10 mg) and experiencing withdrawal bleeding were changed to a continuous daily regimen of 0.3 mg CEE and a random allocation of one of three low-dose progestogens (medroxyprogesterone acetate 2.5 mg, levonorgestrel 30 micrograms or norethisterone 350 micrograms). Return to a dose of 0.625 mg CEE was permitted if required to control menopausal symptoms with separate analysis of this group when appropriate. OUTCOMES MEASURED: Menopausal symptom score, clinical bleeding pattern, endometrial biopsy results, forearm bone density and content, serum lipids and side effects. RESULTS: Fifteen women withdrew from the trial, five because of irregular bleeding. In the remainder, amenorrhoea was achieved in 53% by three months, in 67% by six months and in 93% by 12 months. Endometrial biopsy showed atrophic endometrium by 12 months in all but one patient, in whom minimal proliferative activity was seen. Twenty-seven women chose to return to a dose of 0.625 mg CEE. In all groups, final control of menopausal symptoms improved. All regimens were bone sparing and the lipid profile was unchanged. Minimal side effects were experienced by the patients. There was little difference in outcome between the three progestogens except that norethisterone therapy was associated with a greater prevalence of amenorrhoea at six months than was seen in the levonorgestrel and medroxyprogesterone acetate groups. CONCLUSIONS: These low-dose continuous oestrogen and progestogen regimens appear an appropriate option for the postmenopausal woman wishing to eliminate withdrawal bleeding and reduce both hormonal side effects and menopausal symptoms. The long term benefits of these regimens with regard to the prevention of osteoporotic fractures, cardiovascular disease and endometrial cancer need to be further assessed over time. 相似文献
7.
Eight treatment groups of CD strain castrate male or female rats were injected daily with cottonseed oil (sham), testosterone propionate (50 micrograms/100 g body wt), estradiol benzoate (7 micrograms/100 g body wt), or a combination of both steroids dissolved in cottonseed oil. These physiologic replacement dosages of sex steroids, determined by bioassay procedures, were injected in a 0.1-ml bolus of cottonseed oil daily (intraperitoneally) for 16 weeks. Myocardial anoxic resistance was quantified by means of an in vitro right ventricular strip preparation that evaluated the ability of the isolated right ventricle to maintain contractions in response to electrical pacing at 1 Hz after 10 min of anoxia. While this parameter was elevated 2- to 3-fold in the estrogen-treated groups of male and female castrates compared with the sham (oil)-injected groups, neither testosterone treatment alone nor combination steroid treatment produced anoxic resistance values that differed significantly from those of the sham-injected animals. Thus, although estrogen alone may afford anoxic protection to the myocardium, testosterone is able to abolish this hormone-induced protection. 相似文献
8.
The aim of this study was to determine the effect of a short-term ethinyl estradiol/levonorgestrel medication on blood flow in the uterine arteries in postmenopausal women in a prospective placebo-controlled double-blind study. Twenty-one healthy postmenopausal woman at least 2 years after menopause received 60 micrograms ethinyl estradiol (EE) for 14 days followed by 40 micrograms EE plus 125 micrograms levonorgestrel (LNG) for 12 days (total treatment period 26 days). Sonographically, uterine volume, endometrial thickness, and blood flow in the uterine arteries [as reflected by pulsatility (PI) and resistance indices (RI)] were measured. Uterine size increased from 44 to 80 mL (day 14, p < 0.001) and 87 mL (day 26, p = NS). Endometrium grew from 3 to 8 mm (day 14, p < 0.001) and 11 mm (day 26, p = NS). Uterine arterial PI fell from 2.76 to 1.37 (day 14, p < 0.001) and 1.34 (day 26, p = NS), whereas RI fell from 0.9 to 0.68 (day 14 and day 26, p < 0.001). In conclusion, short-term treatment with LNG does not antagonize the vascular effect of EE on the uterine arteries as reflected by PI and RI. This result might have clinical significance in the selection of the progestin used in hormonal replacement therapy. 相似文献
9.
M Stomati B Hartmann A Spinetti D Mailand S Rubino A Albrecht J Huber F Petraglia AR Genazzani 《Canadian Metallurgical Quarterly》1996,19(8):535-541
Plasma sex hormone-binding globulin (SHBG) levels are important in the regulation of plasma free and albumin-bound androgens and estrogens. In postmenopausal women associated to the decrease of estrogen production, a decrease of plasma SHBG levels occurs. Hormone replacement therapy (HRT) in postmenopausal women modulates plasma SHBG levels, in relationship with the different regimens and routes of administration. The present study aimed to compare the effect of different HRT on plasma SHBG levels in relationship with the changes of plasma androgen [dehydroepiandrosterone sulphate (DHEAS), testosterone (T), androstenedione (A)] and insulin-like growth factor-1 (IGF-1) levels. In a retrospective study 443 postmenopausal women were studied and divided into 2 groups. The group 1 (n = 170) was subdivided in 4 groups of women as follows: A) treated with transdermal 17-beta estradiol + medroxyprogesterone acetate, B) treated with oral conjugated estrogens, C) treated with sequential HRT (estradiol valerate (EV) + norgestrel), and D) treated with a combined HRT (micronized estradiol (E2) + noretisterone acetate). Women of group 2 (n = 273) did not receive HRT and served as controls. All groups of women treated with different HRT showed plasma estradiol levels significantly higher than controls (p < 0.01), showing the highest values in women treated with oral HRT. Plasma SHBG levels were not significantly different between patients treated with transdermal 17-beta estradiol + medroxyprogesterone acetate and controls. On the other hand, all the groups of patients treated with oral conjugated estrogen with or without progestagens showed plasma SHBG levels significantly higher than controls (p < 0.01). Plasma SHBG levels were higher in the group treated with estrogen alone than in groups of women treated with sequential or combined HRT. Plasma DHEAS, T and A levels in patients treated with different HRT regimens were in the same range of levels as control women. Plasma IGF-1 levels were not significantly affected by the various HRT regimens and remained in the same range as controls. In conclusion, plasma SHBG levels increase following oral HRT while are not affected by transdermal HRT. Plasma IGF-1 and androgen levels are not influenced from oral or transdermal HRT. 相似文献
10.
Estrogen replacement therapy in postmenopausal women must be combined with progestin to avoid endometrial cancer. However, progestin addition could antagonize cardioprotective effects of estradiol. Therefore we investigated the effect of the two most commonly used progestins--medroxyprogesterone acetate (progesterone-derivative) and norethisterone acetate (nortestosterone-derivate)--alone and in combination with 17 beta-estradiol on copper-mediated oxidation of low density lipoprotein (LDL). Whereas 17 beta-estradiol alone inhibited the onset of LDL oxidation at the concentrations 0.5, 1.0, 5 and 10 microM, the progestins alone did not demonstrate any significant effect. In the estrogen-progestin combinations of 0.5 microM 17 beta-estradiol with 0.5, 1.0, 5 and 10 microM progestin, respectively, the estradiol effect was not changed. These results suggest that medroxyprogesterone acetate as well as norethisterone acetate do not counteract the beneficial effect of 17 beta-estradiol on LDL oxidation when used in hormone replacement therapy. 相似文献
11.
F Schatz S Aigner C Papp E Toth-Pal V Hausknecht CJ Lockwood 《Canadian Metallurgical Quarterly》1995,80(8):2504-2510
Progesterone acts on the estradiol (E2)-conditioned human endometrium to induce decidualization of stromal cells. Consistent with these differential hormone actions in vivo, progestins regulate several end points of decidualization in human endometrial stromal cell monolayers, and E2 augments the effects of progestin. This study shows that in vitro decidualization of the stromal cells is accompanied by diminished plasminogen activator (PA) expression. Polyacrylamide gel electrophoretic separation after immunoprecipitation of biosynthetically labeled PAs revealed that medroxyprogesterone acetate (MPA) lowered levels of secreted tissue type PA (tPA) at 67 kilodaltons and urokinase type PA (uPA) at 55 kilodaltons. These levels were reduced further by E2 plus MPA despite a lack of response to E2 alone. Although tPA activity was readily measured by a chromogenic assay, detection of uPA activity required prior activation, indicating that uPA is released as the pro-uPA zymogen. Comparisons of levels of immunogenic PAs, as measured by specific enzyme-linked immunosorbent assays, with the corresponding catalytic activities revealed selective progestational inhibition of PA activity vs. antigen after 3 days of experimental incubation. Thus, 10(-7) mol/L MPA produced about a 2-fold greater reduction of levels of PA activity than that of its corresponding antigen. More strikingly, 10(-8) mol/L E2 plus 10(-7) mol/L MPA virtually eliminated both tPA activity (99% inhibition; P < 0.005) and uPA activity (93% inhibition; P < 0.005); the reductions in levels of the corresponding antigens were only about 50% of the control levels and did not attain statistical significance. Only after 3-6 days of incubation with E2 plus MPA was statistically significant inhibition achieved for immunogenic levels of both tPA (P < 0.05) and uPA (P < 0.005). Preferential inhibition of levels of PA activities compared with those of the corresponding PA antigens reflects the action of the potent PA inhibitor PAI-1. Thus, the concentration of PAI-1 in the stromal cell-conditioned medium at the end of 0-3 days exceeded those of tPA and uPA, respectively, by 28- and 12-fold in response to MPA and by 52- and 25-fold in response to E2 plus MPA. Extrapolation of these in vitro results to the events of the luteal phase, whose steroidal milieu is mimicked by E2 plus MPA, indicates that decidual cell-derived PAI-1 is a key regulator of proteolytic degradation of extracellular matrix and fibrinolysis during implantation and menstruation. 相似文献
12.
AM Engel IM Svane S Mouritsen J Rygaard J Clausen O Werdelin 《Canadian Metallurgical Quarterly》1996,104(9):629-639
In order to study the role of the T-cell-mediated immune defense in tumor development, a total of 93 sarcomas were induced using different doses (8 micrograms (0.1%), 40 micrograms (0.5%) and 400 micrograms (5%)) of 3-methylcholanthrene in athymic nude Balb/c mice and phenotypically normal immunocompetent Balb/c mice. A shorter tumor induction time and a higher tumor incidence after treatment with low doses of methylcholanthrene were seen in nude mice than in immunocompetent mice, indicating that they have a lower resistance to the carcinogen. Contrary to expectations we found that the MHC class I expression of tumors from nude mice was lower than that of tumors from normal mice. Higher surface expression of MHC class I was demonstrated on high dose tumors from normal mice than on low dose tumors from normal mice. The cellular composition of the individual tumors raised in nude mice was more heterogeneous with respect to MHC class I expression. Since the mice differ genetically only with respect to the nu gene, these results indicate that a lack of T-cell-mediated defense mechanisms may confer upon the bearer a lower resistance to 3-methylcholanthrene and a different MHC profile of the ensuing tumor. 相似文献
13.
OBJECTIVES: To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas. METHODS: In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared. RESULTS: Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size. CONCLUSIONS: The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE-MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE-MPA therapy, at the doses used here, promote fibroid growth. 相似文献
14.
15.
Stromal fibroblasts in the primate endometrium undergo dramatic morphological and biochemical changes in response to pregnancy. This transformation is characterized by the expression of insulin-like growth factor binding protein-1 (IGFBP-1). Stromal cells from the baboon endometrium of nonpregnant animals were cultured and subsequently treated with cytochalasin D to disrupt actin filaments. In response to cytochalasin D treatment, cells contracted and became rounded as early as 10 min after the initiation of treatment. When cytochalasin D was removed, cells reverted back to their original fibroblastic shape within 1 h. After cells were treated with cytochalasin D for 5 h, addition of (Bu)2cAMP and/or hormones (estradiol, medroxyprogesterone acetate, and relaxin) resulted in the expression of IGFBP-1 messenger RNA and protein within 24 h. Cells with an intact cytoskeleton did not express detectable levels of IGFBP-1 in response to hormones and/or (Bu)2cAMP. Furthermore, the addition of cycloheximide inhibited expression of IGFBP-1 in cytochalasin D-treated cells. Stromal cells were also isolated from early pregnant and simulated pregnant animals. Within 48 h, cells from both the pregnant and simulated pregnant animals produced IGFBP-1 in response to hormones and/or (Bu)2cAMP. In these studies, IGFBP-1 expression was also inhibited by cycloheximide. These studies suggest that induction of IGFBP-1 requires an intermediary protein and that alterations in the cytoskeleton may be involved. 相似文献
16.
KO Klein J Baron KM Barnes OH Pescovitz GB Cutler 《Canadian Metallurgical Quarterly》1998,83(7):2387-2389
Although treatment of girls with precocious puberty should ideally restore estradiol levels to the normal prepubertal range, treatment effectiveness has usually been monitored by gonadotropin levels because estradiol RIAs have lacked sufficient sensitivity to monitor treatment effectiveness. We hypothesized that a recently developed ultrasensitive recombinant cell bioassay for estradiol would have sufficient sensitivity to demonstrate a dose-dependent suppression of estradiol during LH-releasing hormone agonist treatment and to determine whether currently used doses are able to suppress estradiol levels to the normal prepubertal range. Twenty girls with central precocious puberty were assigned randomly to receive deslorelin for 9 months at a dose of 1, 2, or 4 micrograms/ kg.day. A significant dose-response relationship was observed, with mean +/- SD estradiol levels of 16.7 +/- 6.1, 7.9 +/- 1.6, and 6.5 +/- 0.7 pmol/L at the doses of 1, 2, and 4 micrograms/kg.day, respectively (P < 0.01). The highest dose suppressed estradiol levels to just above the 95% confidence limits for normal prepubertal girls (< 0.07-6.3 pmol/L). We conclude that the ultrasensitive bioassay for estradiol has sufficient sensitivity for monitoring the response to LH-releasing hormone agonist treatment of central precocious puberty. Additionally, the observation that the deslorelin dose of 4 micrograms/kg.day did not fully restore estradiol levels to the normal prepubertal range suggests that some girls with precocious puberty may require higher doses to receive the maximal benefit of treatment. We suggest that restoration of estradiol levels to the normal prepubertal range should be the ultimate biochemical measure of efficacy, as estradiol is the key hormone that accelerates growth rate, bone maturation rate, and breast development in girls with precocious puberty. 相似文献
17.
A Guglielmotti L Aquilini MT Rosignoli C Landolfi L Soldo I Coletta M Pinza 《Canadian Metallurgical Quarterly》1997,46(9):332-335
OBJECTIVE: Previous studies have shown that benzydamine (40 mg/kg s.c.) is able to inhibit tumor necrosis factor (TNF) production and to reduce mouse lethality when administered before or concomitantly with LPS. The present study was designed to further investigate benzydamine activity against LPS-induced toxicity in terms of potency and therapeutic effects. METHODS: Female Balb/c mice were used. A dose-response curve of animal lethality versus endotoxin dose was performed (LD50 = 45 micrograms/mouse). Therapeutic effects were studied selecting the dose of LPS to achieve an LD100 (160 micrograms/mouse). Mortality was assessed daily and mice were followed for 8 days. The potential mode of action of therapeutically administered benzydamine was also investigated. TNF alpha and IL-1 beta levels were measured, at 5 h after LPS injection, both in sera and in lungs. Moreover, the drug was assayed in a TNF-dependent cytoxicity test. RESULTS: Benzydamine, administered at 20 mg/kg s.c. simultaneously with the endotoxin, significantly increased LPS LD50 up to 230 micrograms/mouse (p < 0.05). Moreover, the drug significantly protected mice against LPS-induced lethality when administered either 30 min or 4 h after endotoxin injection (p < 0.001). Benzydamine, therapeutically administered at 20 mg/kg s.c., significantly reduced TNF alpha and IL-1 beta production induced by LPS both in serum and lungs and it was shown to inhibit TNF-dependent cytoxicity on L929 cells. CONCLUSIONS: These results clearly demonstrate the therapeutic activity of benzydamine in a simple model of endotoxic shock. Available data confirm the potential role of benzydamine as an anti-cytokine agent and provide suggestions for novel therapeutic applications of this anti-inflammatory drug. 相似文献
18.
We have previously reported that a synthetic peptide corresponding to amino acid residues 81-95 of the human (h) FSH-beta subunit inhibited binding of [125I]hFSH to bovine calf testis membranes and stimulated estradiol biosynthesis in primary cultures of rat Sertoli cells. We have now obtained several lines of evidence demonstrating in vivo effects of hFSH-beta-(81-95) on the mouse estrous cycle. 1) A single i.p. injection of 200 micrograms/g BW hFSH-beta-(81-95) significantly (p < 0.001) prolonged vaginal estrus in comparison to that in vehicle-injected control mice. 2) Vaginal smears taken at estrus from mice given hFSH-beta-(81-95) were characterized by the complete absence of epithelial casts, a hallmark of spontaneous ovulation in mice. 3) Mice receiving hFSH-beta-(81-95) had significantly (p < 0.001) lower serum estradiol at proestrus and serum progesterone at diestrus than vehicle-injected control mice. 4) The proestrous effects of estrogen on uterine ballooning and weight gain, clearly evident in vehicle-injected control mice, were not observed in mice treated with hFSH-beta-(81-95). A synthetic peptide corresponding to the carboxy-terminal region of hFSH-beta-(81-95), hFSH-beta-(90-95), inhibited binding of [125I]hFSH to bovine calf testis membranes, antagonized FSH-stimulated estradiol biosynthesis by primary cultures of rat Sertoli cells, and prolonged vaginal estrus in normally cycling mice. A synthetic peptide corresponding to the amino-terminal domain, hFSH-beta-(81-86), was inactive in vitro and had no effect on the mouse estrous cycle. The results of the present study provide additional evidence for in vivo effects of FSH-related synthetic peptides. 相似文献
19.
MC St Claire LK Riley CL Franklin CL Besch-Williford RR Hook 《Canadian Metallurgical Quarterly》1994,44(5):430-435
Studies were initiated to establish and maintain intravaginal Tritrichomonas foetus infections in female BALB/c mice as a model for elucidation of parasite and host factors that affect the course of vaginal protozoan infections. Results of these studies indicated that T. foetus infections could only be established in mice in which estrus was induced and maintained. Over a period of several weeks, mice induced to estrus by weekly administration of estradiol cypionate exhibited purulent vaginal discharge and perivulvar abscesses. Implantation of silastic tubing containing 15 micrograms of estradiol-17 beta proved effective in induction and maintenance of estrus and avoided the animal health problems associated with estradiol cypionate treatment. Results of quantitative experiments indicated that the duration of trichomonad infection was influenced by initial colonization of the vagina, i.e., mice with high numbers of vaginal trichomonads at 7 days after infection maintained infections longer than did mice with lower numbers of vaginal parasites. Weekly administration of either 2 or 4 mg of methylprednisolone acetate to estrogenized mice did not extend the duration of T. foetus infections, thereby suggesting that the immune response did not limit the establishment and maintenance of primary vaginal trichomonad infections. Study of estrogenized BALB/c nu/nu mice supported these observations in that establishment of T. foetus infections was difficult in nu/nu mice and that, in most nu/nu mice (76%), the course of infection was not lengthened (mean, 1.9 weeks). When examined by electron microscopy, the earliest lesions were characterized by degeneration and necrosis of chondrocytes, along with degradation of cartilage matrix. These findings confirm that quinolone arthropathy develops in juvenile rabbits and is similar to quinolone arthropathy in other laboratory animals.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
20.
OBJECTIVE: To evaluate the relation between the development of the uteroplacental circulation as assessed by Doppler velocimetry and the maternal blood relaxin concentration. METHODS: Transvaginal color Doppler investigation of the uteroplacental circulation was performed in 42 healthy women at 6-15 weeks' gestation before termination of pregnancy for psychosocial reasons. The resistance index (RI), pulsatility index (PI), and maximum peak velocity were recorded at the level of the main uterine artery, and the presence of intervillous flow was noted. Relaxin, hCG, 17 beta-estradiol (E2), and progesterone levels were measured in maternal venous blood. RESULTS: Limited intervillous flow was noted from 10 weeks' gestation and continuous intervillous flow from 12 weeks. An inverse relation was observed between the circulating levels of both E2 and progesterone and uterine artery RI and PI, whereas the relaxin level correlated positively with uterine RI and PI. Estradiol and progesterone levels also correlated positively with uterine peak systolic velocity and intervillous blood flow. Multiple linear regression analysis indicated that both hormones contributed to the decrease in downstream resistance to uterine blood flow with advancing gestational age, as assessed by uterine RI. In addition, relaxin contributed to the uterine RI and PI and to the intervillous blood flow. CONCLUSION: These data suggest that relaxin, E2, and progesterone may influence the changes in uterine blood flow that occur in early pregnancy. The role played by E2 and progesterone in the development of the uteroplacental circulation may be modulated by relaxin, constituting a novel function for this ovarian peptide. 相似文献