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1.
Femalerhesus macaques show monthly menstrual cycles and eventually enter menopause at approximately 25 yr of age. To help identify early biomarkers of menopause in this nonhuman primate, we monitored reproductive hormones longitudinally from aged female macaques during the transitions from premenopause to perimenopause and postmenopause and found that, indeed, elevated plasma FSH was a better predictive factor of menopause onset than age. In a second experiment, we compared reproductive hormone profiles of young adult macaques (8-10 yr old) with those of regularly cycling old macaques (approximately 24 yr old). Indwelling vascular catheters were used for remote blood collection for at least 100 consecutive days, thereby covering three complete menstrual cycles in each macaque. Plasma levels of estradiol, progesterone, LH, FSH, follicular phase inhibin B, and anti-müllerian hormone (AMH) were determined during each menstrual cycle and were averaged for each animal; group mean differences were analyzed using one-way ANOVA. Old premenopausal macaques showed regular menstrual cycles that were qualitatively indistinguishable from those of young macaques; peak plasma levels of estradiol, progesterone, and LH were not significantly different. In marked contrast, peak plasma FSH concentrations were significantly higher, while inhibin B and AMH levels were generally lower, in the old premenopausal macaques compared with those in the young macaques. These data provide further evidence that rhesus macaques serve as an excellent model to study underlying mechanisms of human menopause. Furthermore, the data suggest that an age-related change in FSH, inhibin B, and AMH secretion may be the first endocrine manifestation of the transition into perimenopause, potentially having value in predicting the onset of the perimenopausal transition. 相似文献
2.
C P Puri R R Katkam A D Vadigoppula K Gopalakrishnan W A Elger F R Billimoria R K Patil 《Indian journal of experimental biology》1992,30(11):987-995
Studies were undertaken in adult bonnet monkeys to investigate whether treatment with an antiprogestin ZK 98.734 at weekly intervals, starting from day one of menstrual cycle, could arrest ovulation and also to determine if ZK 98.734 induced blockade of ovulation could be reversed with gonadotropins. Adult animals have ovulatory menstrual cycles of normal duration were treated at weekly intervals with ZK 98.734 (25 mg/dose, sc, oil base) for 10 consecutive weeks and its effects on serum levels of estradiol, bioactive LH and progesterone, and endometrial histology were investigated. Following treatment with the antiprogestin they were treated with hMG or hFSH alone. Ovulation was blocked during treatment period in all the animals (n = 14). Typical follicular phase rise in estradiol levels was inhibited, mid cycle surge in the levels of bioactive LH was abolished and serum progesterone levels remained below 1 ng/ml throughout the treatment period. However, prolonged treatment had no significant effect on the basal levels of estradiol which were around 50 pg/ml. ZK 98.734 also had no significant effect on cortisol levels. In animals (n = 4) followed for recovery after the last dose, the treatment cycle length was increased to 117.8 + 6.8 days. In three animals the treatment cycles were anovulatory, whereas in one delayed ovulation with luteal insufficiency was observed. The endometrium had become atrophic. Treatment with hMG (Pergonal: 35 I.U. hLH and 35 I.U. hFSH) or hFSH (Metrodin, 35 I.U.) for 7 consecutive days initiated folliculogenesis and the animals ovulated either spontaneously or after a single im injection of hCG (100 I.U.) on day 8 in ZK 98.734 treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
Implicit motives for power and affiliation, salivary levels of testosterone, estradiol, and progesterone, and relationship status were measured in 18 normally cycling (NC) women, 18 women using oral contraceptives (OC), and 18 men at three assessments, corresponding to the menstrual, midcycle, and premenstrual phases of women's menstrual cycle. NC and OC women had elevated levels of affiliation motivation and decreased levels of power motivation at midcycle. Power motive changes were particularly pronounced in NC women across cycle phases. OC women and participants not engaged in an intimate relationship had significantly heightened levels of affiliation motivation, averaged across all cycle phases. Testosterone and power motivation, both averaged across all cycle phases, were positively correlated in men and in single women, but not in women engaged in an intimate relationship. Averaged levels of estradiol and power motivation were positively correlated in engaged women, but not in single women or men. Averaged levels of progesterone and affiliation motivation were negatively correlated in men, and there was evidence for a positive association between luteal affiliation motivation and periovulatory and luteal progesterone in NC women. This study therefore provides evidence that implicit motivational states fluctuate across the menstrual cycle, that the power motive is associated with testosterone and, in women, with estradiol, and that the affiliation motive and progesterone are associated in different ways in men and NC women. 相似文献
4.
Makoto Moro Ryuzo Torii Hajime Ishii Yoshikuni Tanioka Yoichi Inada Masami Kojima Hirotada Tsujii 《Primates; journal of primatology》2001,42(4):375-390
We investigated the relationship between the menstrual cycle and hormone levels in cynomolgus monkeys, and developed a sulpiride-induced
hyperprolactinemic anovulation model. On this study, we demonstrated the usefulness of the commercial human prolactin immunoradiometric
assay kit for the measurement of cynomolgus monkey serum samples. In the normal menstrual cycle of the cynomolgus monkey,
serum prolactin concentrations were not significantly different between luteal and follicular phases. However, the serum prolactin
concentration tended to elevate at the ovulation stage. And serum progesterone began to increase after an estradiol surge,
and then declined before the ensuing preovulatory rise in estradiol. During the luteal phase, the serum concentration of progesterone
was elevated. Moreover, we aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in the cynomolgus
monkey. The serum prolactin level gradually increased during the twice-daily administration of sulpiride, and the drug produced
as big a response at 5 mg/kg. In this study, the length of the menstrual cycle was approximately 29 days in normal cynomolgus
monkeys. When treatment with sulpiride had been continued for more than one month, serum progesterone and estradiol levels
fell to within the range seen in the follicular phase of the normal cycle, and the absence of ovulation was recognized by
laparoscopy. Moreover, in this period we found that amenorrhea or anovulatory menstruation in the experimental animals. We
could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. Our findings suggest
that the cynomolgus monkey is useful as a endocrinological model that uses prolactin as a parameter and as an anovulatory
model; thus, it could be a useful model for the hyperprolactinemic amenorrhea and/or anovulation seen in humans. 相似文献
5.
6.
We used sequential treatment with implants of estradiol (E2) and progesterone (P) to create varied hormonal states in a group of spayed cynomolgus macaques. The reproductive tracts were removed, and nuclear and cytosolic estrogen receptors were analyzed in the cervical mucosa, endometrium, and oviducts. Nuclear receptor quantities were greater in tissues of E2-treated monkeys than in tissues of spayed animals. Sequential P treatment, even in the presence of continuous E2, decreased the amounts of nuclear and cytosolic E2 receptors. In the oviduct and endometrium, the P-mediated suppression of receptors occurred within 1 or 2 days. In the cervix, suppression occurred only if the serum P:E2 ratio was elevated to twice the amount (approximately 100:1) usually found during the luteal phase of the menstrual cycle (approximately 50:1) in this species. Of these three reproductive tract tissues, the cervix had the highest threshold for suppression by P of E2 receptors in the presence of E2. 相似文献
7.
The effects of a progesterone antagonist, lilopristone (ZK 98.734), on induction of menstruation, inhibition of implantation or pregnancy, and termination of early and mid-pregnancy were studied in bonnet monkeys. In the regularly menstruating animals, administration of lilopristone (25 mg/day, s.c.) during the mid-luteal phase (Days 20-22 of the menstrual cycle) induced menstruation within 2-4 days after the initiation of treatment. A premature drop in circulating progesterone levels was also observed. The luteolytic effect of lilopristone was prevented by exogenous treatment with hCG; however, the animals showed premature menstruation, in spite of high progesterone levels (above 4 ng/ml). Treatment around the time of implantation (between Days 8 and 12 after the mid-cycle peak in estradiol levels) in mated animals provided 100% pregnancy protection. Treatment of pregnant animals on Days 30-32 of the menstrual cycle, i.e. about Day 20 after the estradiol peak, induced abortion in 8 of 10 animals. A significant (p less than 0.05) decrease in serum progesterone levels was observed on Day 3 after the initiation of treatment. However, the decrease was slower (slope: -0.36, r: 0.96) compared to that observed in nonpregnant animals (slope: -0.72, r: 0.95). In the other two animals, pregnancy was not affected. However, when the treatment was delayed until about Day 50 after the estradiol peak, all four animals aborted. This study suggests that lilopristone is a progesterone antagonist with a potential to induce menstruation, inhibit nidation, and terminate pregnancy. The antifertility effects are mediated through blocking progesterone action at the endometrium as well as decreasing progesterone bioavailability, which appears to be due to its effects on gonadotropin release. 相似文献
8.
Immunoreactive 10.5 KDa moiety of inhibin and hFSH was present in the baboon endometrium during menstrual cycle, early pregnancy and in castrated animals treated with steroid hormones, estrogen and/or progesterone. Endometrial differences during the menstrual cycle altered the intensity of immunostaining of inhibin and FSH. Maximum staining was observed in late luteal phase for both the hormones. In early pregnancy (35th day), the conceptus increased the staining for inhibin in the adjoining endometrial glands. Treatment of castrated animals with steroids for 14 days caused increased staining for inhibin. Maximum staining was observed when treated with estradiol or progesterone, whereas combination of estrogen and progesterone treatment decreased the staining reaction. In conclusion, both inhibin and FSH were localized in baboon endometrium and were under the influence of estrogen and progesterone. 相似文献
9.
Daily measurement of serum luteinizing hormone, estradiol-17beta, and progesterone were made during the menstrual cycle in nine pigtail macaques (Macaca nemestrina). All data were normalized to the day of the luteinizing hormone peak. Serum estradiol-17beta increased from approximately 100 pg/ml during the early follicular phase to 442 +/- 156 pg/ml during the maximum midcycle concomitant with the luteinizing hormone peak, and a small increase in serum estradiol-17beta was observed during the luteal phase coincident with the progesterone peak. Serum progesterone values increased slightly at the time of the luteinizing hormone peak and increased from 0.2-0.3 ng/ml during the midfollicular phase to peak levels of 8.3 +/- 1.75 ng/ml 9 days after the luteinizing hormone surge. Serum luteinizing hormone remained low and relatively constant throughout the early and midcycle, then sharply increased approximately four-fold to peak values of 6.25 +/- 0.9 ng/ml. Sex skin swelling increased slowly during the follicular phase and declined slowly throughout the early luteal phase. Rectal temperature did not change significantly throughout the menstrual cycle. The similarity of plasma sex hormone changes during the menstrual cycle between women and the pigtail macaque suggested that this nonhuman primate should be a useful animal model for studying human reproduction. 相似文献
10.
Henning T Fakile Y Phillips C Sweeney E Mitchell J Patton D Sturdevant G Caldwell HD Secor WE Papp J Hendry RM McNicholl J Kersh E 《Journal of medical primatology》2011,40(4):214-223
Background Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIVSF162P3. Methods Seven SHIVSF162P3‐infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy. Results Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7–10 post‐infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics. Conclusions These pilot studies demonstrate the first successful STI‐SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans. 相似文献
11.
G. Maffeo R. Ballabio V. Olgiati F. Guidobono 《Prostaglandins & other lipid mediators》1983,25(4):541-548
A new analogue of PGFα, alfaprostol, was used to induce estrus in normally cycling and anestrous cows.Five groups of six animals were treated with single injections of different doses of the drug (4, 5, 6, 7 or 8 mg/animal) on day 10–11 of the estrous cycle. Six cows in anestrus, with palpable corpora lutea, were treated i.m. with 8 mg/animal. The luteolytic properties of alfaprostol were assessed by measuring milk progesterone by RIA for 96 h after treatment and by checking for the subsequent signs of estrus. The dose of 4 mg caused a slight fall in progesterone but did not induce heat; the 5 and 6 mg doses induced estrus in
animals and the 7 mg dose was effective in
animals. The 8 mg dose produced a sharp reduction in milk progesterone within 24 h, followed by estrus in both the normally cycling and the anestrous groups in
animals. No clinical signs of drug intolerance were seen. The present results show that alfaprostol might be of great use for both cycle synchronization in normally cycling cows and for treatment of anestrus caused by a persistent corpus luteum. 相似文献
12.
13.
Peripheral levels of progesterone and estradiol 17beta were quantified in 27 cycling cows following administration of a single Hydron ear implant (G. D. Searle and Co.) containing 2, 4 or 6 mg norgestomet or controls which received no implant. Implants were inserted subcutaneously in the ear on day 15 of the estrous cycle (day of estrus = day 0) and removed 9 days later. The 4 mg (seven of seven cows) and 6 mg (six of six cows) implants suppressed estrus; however, three of eight cows in the 2 mg group exhibited estrus prior to implant removal. The 6 mg implant group had a significantly longer interval from implant removal to estrus than either the 2 or 4 mg group. Failure to detect differences in the rate at which progesterone declined indicated norgestomet treatment did not affect normal corpus luteum regression. Estradiol levels rose at a similar rate approaching estrus in all treatments. There was no indication of increased endogenous estradiol levels due to norgestomet treatment. 相似文献
14.
Gopalkrishnan K Katkam RR Sachdeva G Kholkute SD Padwal V Puri CP 《Biology of reproduction》2003,68(6):1959-1967
Our previous studies demonstrated the ability of low doses of antiprogestin ZK 98.299 (onapristone) to inhibit fertility in bonnet monkeys. In the present study cumulative effects of low doses of ZK 98.299 on the endometrial cytoarchitecture of bonnet monkeys were analyzed. Treatment with either the vehicle (n = 3) or onapristone at 2.5 mg (n = 4) or 5.0 mg (n = 3) was initiated on Day 5 of the first menstrual cycle and thereafter repeated every third day for four to seven consecutive cycles. The last treatment cycles were anovulatory in two animals treated with 2.5 mg and all animals treated with 5.0 mg. Endometrial biopsies were collected on Day 8 after the midcycle estradiol peak in ovulatory menstrual cycles and on Day 20 in anovulatory menstrual cycles during the last treatment cycle. Ultrathin sections of the fixed endometrium were stained with toluidine blue for morphometric analysis and uranyl acetate and lead citrate for ultrastructural analysis. The ZK 98.299-treated animals showed a dose-dependent endometrial atrophy as evident by a decrease in the height and diameter of the glands and early signs of compaction in the stroma. Ultrastructural analysis also revealed dose-dependent degenerative changes in the subcellular organelles such as the nucleus, mitochondria, endoplasmic reticulum, lysosomes, and Golgi apparatus. This suggests that long-term treatment with low doses of ZK 98.299 leads to the suppression of estrogen-dependent endometrial proliferation. However, this blockade operates independent of estradiol receptor (ER) and progesterone receptor (PR) concentrations as the expressions of these steroid receptors did not show any significant changes even after prolonged treatment. The study demonstrated an antiestrogenic effect of ZK 98.299 on endometrium after prolonged treatment in bonnet monkeys. 相似文献
15.
Normally cycling Rhesus monkeys were treated with diethylstilbestrol (25 mg/day) alone or in combination with indomethacin (25 mg/day) for five consecutive days beginning in the early luteal and mid-luteal phase of the menstrual cycle. Blood specimens were obtained daily to monitor corpus luteum function (progesterone), and the length of each menstrual cycle was recorded. Diethylstilbestrol alone cause premature luteolysis as indicated by decreasing plasma progesterone and shortened menstrual cycle, and indomethacin effectively blocked the luteolytic action of diethylstilbestrol. These results suggest that the probable mechanism of diethylstilbestrol action in causing luteolysis is mediated via the prostaglandins. 相似文献
16.
Wei Wang Zhe Cong Xiuying Liu Wei Tong Hongwei Qiao Hong Jiang Qiang Wei Chuan Qin 《Journal of medical primatology》2010,39(6):374-380
Background In Indian rhesus macaques, the major histocompatibility complex Mamu gene, especially the Mamu‐A*01 allele, plays an important role in simian immunodeficiency virus susceptibility and disease progression. The Mamu‐A*01 allele is one of the protective genes mostly being studied in simian acquired immunodeficiency syndrome. Methods PCR was used to amplify the Mamu‐A*01 allele in 130 Chinese‐origin rhesus macaques. Identification of the allele was then confirmed by sequencing and IFN‐γ ELISPOT assay. Results The Mamu‐A*01 allele was detected in 3.85% (5 of 130) of the experimental Chinese‐origin rhesus macaques. The sequence homology reached 99.1% in comparison with Indian rhesus macaques. A significantly large number of spots were observed in Mamu‐A*01‐positive monkeys when analyzed by ELISPOT with Gag181‐189 epitope stimulation. Conclusions Our study suggests that Mamu‐A*01‐positive Chinese‐origin rhesus monkeys are suitable for use in AIDS studies. 相似文献
17.
《Prostaglandins and medicine》1979,2(3):191-201
Prostalene, a synthetic prostaglandin (PG) analog was compared to PGF2α for ability to both shorten the luteal phase and to terminate early, confirmed,pregnancy in the rhesus macaque. 15mg of either prostalene or PGF2a administered as a single intramuscular injection 30 days from last menstrual bleed aborted all treated animals. In contrast, while a single dose of 15mg of prostalene administered 7 days before expected menstruation to regularly cycling, non-pregnant monkeys shortened the luteal phase by 5.0 ± 0.7 days, the same dose regimen of PGF2a was ineffective whether judged by circulating levels of progesterone or by menstrual cycle length. Mean, peripheral, plasma progesterone levels in the non-pregnant monkeys declined abruptly following prostalene treatment. Although menstrual flow was of normal duration, the cycle length following the prostalene treated cycle was greater than pretreatment cycle lengths, suggesting that follicular maturation was not accelerated after treatment. Experiments in the mare and pregnant hamster demonstrated that a two fold increase in dose above the luteolytic dose of prostalene was required to ensure immediate return of ovulation. It is suggested that prostalene demonstrates both luteolytic and hypothalamo-pituitary stimulating properties but at different dose levels. The compound may thus be useful in dissecting the differing biological mechanisms concerned. 相似文献
18.
A regimen of progesterone plus estradiol (P&E) was used as a standard for ovarian synchronization to test the efficacy and evaluate the commercial application of ultrasound-guided follicle ablation as a non-steroidal alternative for ovulation synchronization in mares. Recipient mares at a private embryo transfer facility were at unknown stages of the estrous cycle at the start of the experiment on Day 1 when they were randomly assigned to an ablation group (n=18-21 mares) or to a P&E group (n=20-21 mares). In the ablation group, mares were lightly sedated and all follicles > or = 10 mm were removed by transvaginal ultrasound-guided follicle aspiration. In the P&E group, a combination of progesterone (150 mg) plus estradiol (10mg) prepared in safflower oil was given daily (im) for 10 d. Two doses of prostaglandin F(2alpha) (PGF, 10mg/dose, im) were given 12 h apart on Day 5 in the ablation group, or a single dose on Day 10 in the P&E group. Human chorionic gonadotropin (hCG, 2500 IU/mare, im) was given at a fixed time, 6 and 10 d after PGF treatment in the ablation and P&E groups, respectively, with the expectation of a follicle > or = 30 mm at the time of treatment. In both the ablation and P&E groups, transrectal ultrasonography was done at the start of the study (Day 1) and again on the day of hCG treatment and daily thereafter to determine the presence of a CL, measure diameter of the largest follicle and detect ovulation. The mean interval from the start of the study and from PGF treatment to ovulation was shorter (P<0.0001) in the ablation group (13.7 and 9.7 d, respectively) compared to the P&E group (22.3 and 13.2 d, respectively). Following fixed-day treatment with hCG after PGF treatment, the degree of ovulation synchronization was not different (P>0.05) between the ablation and P&E groups within a 2-d (56 and 70%) or 4-d (83% and 90%) period. Although ultrasound-guided follicle ablation may not be practical in all circumstances, it excluded the conventional 10-d regimen of progesterone and estradiol and was considered an efficacious and feasible, non-steroidal alternative for ovulation synchronization in mares during the estrous cycle. 相似文献
19.
These experiments were designed to evaluate whether removal of approximately 95% visible ovarian tissue would interrupt the short- or long-term regulation of cyclic ovarian function. On cycle Days 2 4 (onset of menses = Day 1), the entire left ovary and approximately 90% of the right ovary were removed from three cycling cynomolgus monkeys. After approximately 95% ovariectomy, there was an acute elevation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which lasted 11 +/- 2 days. A midcycle-like gonadotropin surge occurred 20 +/- 3 days following approximately 95% ovariectomy; the next menses occurred 19 +/- 1 days later. Follicular phase patterns of estradiol preceded the midcycle gonadotropin surge, and luteal phase progesterone levels indicated subsequent ovulation. Two of three monkeys resumed normal menstrual cyclicity in the following cycle with follicular phase, luteal phase, and menstrual cycle lengths similar to pretreatment levels. Histological examination of the ovarian remnant removed on Day 21 of the next cycle revealed a morphologically normal corpus luteum and many small follicles. A second group of 6 rhesus monkeys also underwent approximately 95% ovariectomy for long-term evaluation of menstrual cyclicity; typical 28-day menstrual cycle patterns were observed in 4 of the 6 monkeys for 5 mo, with 2 of these 3 animals maintaining regular menstrual cycles for 1 yr. In summary, our data suggest that normal ovarian function, i.e. recruitment, selection, and dominance of the ovulatory follicle, ovulation, and subsequent corpus luteum function, is maintained with only approximately 5% of functional ovarian tissue remaining.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
20.
S. Bhargava Periwal A. Farooq V.L. Bhargava N. Bhatla U. Vij K. Murugesan 《Prostaglandins & other lipid mediators》1996,51(3):191-201
Phospholipase A2 activity was studied in isolated human endometrial predecidual cells, and in human endometrium collected from day 19–23 of the menstrual cycle, by performing a radiochemical assay. Phospholipase A2 activity on day 20 was significantly higher than other days (P < 0.001), and the activity was found to gradually decrease after day 20 of the menstrual cycle. The effects of the hormones estradiol and progesterone, and antihormones tamoxifen and RU 486, were studied on the phospholipase A2 activity in isolated predecidual stromal cells. Estradiol produced a significant stimulatory effect (P < 0.001) on phospholipase A2 activity in predecidual cells, and this effect was antagonized by tamoxifen. The combination of estradiol and tamoxifen was significantly different from estradiol alone (P < 0.001), but not from tamoxifen alone. RU 486 alone significantly increased (P < 0.001) phospholipase A2 activity in predecidual stromal cells. However, progesterone had no effect on phospholipase A2 activity in predecidual stromal cells. 相似文献