scholarly journals Musashi as a Regulator of the Follicle-Stimulating Hormone in the Gonadotropes

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A545-A545
Author(s):  
Ana Rita Silva Moreira ◽  
Alexandra Lagasse ◽  
Anessa Haney ◽  
Ulrich Boehm ◽  
Michael G Kharas ◽  
...  

Abstract The cyclic expression of gonadotropin releasing-hormone receptors (GnRHR), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by pituitary gonadotropes is critical in the female reproductive process. We have shown that the translational regulator Musashi (MSI) binds to Gnrhr mRNA and inhibits its translation, and the gonadotrope-specific deletion of Msi1 and Msi2 (Gon-Msi-null) leads to increased pituitary GnRHR protein levels. An in silico analysis of gonadotropin mRNAs revealed 5 different MSI binding elements in the 3’UTR of Fshb mRNA. We hypothesize that, in addition to Gnrhr, MSI may also bind and repress Fshb mRNA translation in the gonadotropes. To test if MSI does target the Fshb transcript in the pituitary, we performed RNA immunoprecipitation (IP) on pooled control female mouse pituitaries using a MSI1 antibody and measured Fshb mRNA by qRT-PCR. To study the in vivo effects of MSI on Fshb, we harvested the pituitaries of the Gon-Msi-null (MUT) female mice and their littermate controls (CTL) during the estrous cycle. We collected serum and protein for EIAs to measure the levels of FSH and LH, and RNA for Fshb qRT-PCR. We harvested proestrous ovaries and fixed them for embedding, sectioning, and H&E staining. Our RNA IP experiments show a 7-fold enrichment for Fshb with the MSI1 antibody. The Gon-Msi-null females have significantly higher pituitary FSH protein content than controls on estrous morning (MUT: 4.8±1.3 vs. CTL: 1.8±2.6 ng/ml/μg protein, p<0.0001, n=9-10/group). These mice also have increased serum FSH levels (MUT: 56.9±6.4 vs. CTL: 44.5±9.6 ng/ml, p=0.0147, n=9-10/group). No changes at the Fshb mRNA level were detected. Analysis of Gon-Msi-null ovaries revealed a 50% decrease in the number of follicles, with significant decreases in the average numbers of maturing follicles (p<0.0175) and corpora lutea (p<0.0215). Interestingly, the LH levels in these mice were also altered. The Gon-Msi-null females show a decrease in the pituitary LH protein content in the evening of proestrus (MUT: 11.8±1.4 vs. CTL: 15.1±2.0 ng/ml/μg protein, p=0.0333, n=7/group), in addition to a delayed and blunted LH surge (MUT: 2.6±1.9 vs. CTL: 7.3±3.5 ng/ml, p=0.0089, n=7-11/group). Taken together, our data indicate that Fshb is a Musashi target in the gonadotropes. By deleting MSI from the pituitary gonadotropes, we observe an increase in FSH protein content and serum levels. These Gon-Msi-null female mice have significantly fewer maturing follicles and corpora lutea, which might suggest lower levels of estrogens and progesterone. This, together with the increased GnRHR pituitary protein content, affects LH secretion, leading to a blunted LH surge in the Gon-Msi-null females. Our studies thus reveal a novel translational regulatory mechanism to govern levels of critical reproductive hormones in the pituitary.

Author(s):  
Erkan Pehlivan ◽  
Hüseyin Polat ◽  
Gürsel Dellal

In this research, annual changes of melatonin, gonadotropin-releasing hormone, follicle stimulating hormone, luteinizing hormone, estrogen, testosterone and progesterone were studied on 6 heads of 1.5 years old female Angora goat. To determine hormones concentrations, blood samples were taken from jugular vein of each goat in every month for a year. The blood samples were centrifuged at 4000xg for 5 min. and serum was stored at -20°C until analyses time. Hormones analyses in the serum were performed by enzyme immunoassay (EIA) method. Monthly climatic values and photoperiod were obtained from the Turkish State Meteorological Service and temperature-humidity index was calculated with climatic values. In the study, in order to determine any possible differences in the observed hormones concentrations with respect to months, repeated measures ANOVA analysis was performed. As a result of statistical analysis, there were no significant differences among the months for gonadotropin-releasing hormone, follicle stimulating hormone and testosterone concentration, while significant differences were found among the months for melatonin, luteinizing hormone and progesterone, and estrogen concentration in female Angora goats. According the results of this study, could be concluded that the releases of reproductive hormones examined in female Angora goats was seasonally dependent.


Author(s):  
Kaitlin R Karl ◽  
Fermin Jimenez-Krassel ◽  
Emily Gibbings ◽  
Janet L H Ireland ◽  
Zaramasina L Clark ◽  
...  

Abstract When women with small ovarian reserves are subjected to assisted reproductive technologies, high doses of gonadotropins are linked to high oocyte and embryo wastage and low live birth rates. We hypothesized that excessive follicle-stimulating hormone (FSH) doses during superovulation are detrimental to ovulatory follicle function in individuals with a small ovarian reserve. To test this hypothesis, heifers with small ovarian reserves were injected twice daily for 4 days, beginning on Day 1 of the estrous cycle with 35, 70, 140, or 210 IU doses of Folltropin-V (FSH). Each heifer (n = 8) was superovulated using a Williams Latin Square Design. During each superovulation regimen, three prostaglandin F2α injections were given at 12-h interval, starting at the seventh FSH injection to regress the newly formed corpus luteum (CL). Human chorionic gonadotropin was injected 12 h after the last (8th) FSH injection to induce ovulation. Daily ultrasonography and blood sampling were used to determine the number and size of follicles and corpora lutea, uterine thickness, and circulating concentrations of estradiol, progesterone, and anti-Müllerian hormone (AMH). The highest doses of FSH did not increase AMH, progesterone, number of ovulatory-size follicles, uterine thickness, or number of CL. However, estradiol production and ovulation rate were lower for heifers given high FSH doses compared to lower doses, indicating detrimental effects on ovulatory follicle function.


2013 ◽  
Vol 305 (6) ◽  
pp. E717-E726 ◽  
Author(s):  
Xiaobing B. Cheng ◽  
Mark Jimenez ◽  
Reena Desai ◽  
Linda J. Middleton ◽  
Shai R. Joseph ◽  
...  

Homozygous androgen receptor (AR)-knockout (ARKO) female mice are subfertile due to both intra- and extraovarian (neuroendocrine) defects as defined by ovary transplantation. Using ARKO mice, this study set out to reveal the precise AR-regulated pathways required for optimal androgen-regulated ovulation and fertility. ARKO females exhibit deficient neuroendocrine negative feedback, with a reduced serum luteinizing hormone (LH) response to ovariectomy (OVX) ( P < 0.01). Positive feedback is also altered as intact ARKO females, at late proestrus, exhibit an often mistimed endogenous ovulatory LH surge. Furthermore, at late proestrus, intact ARKO females display diminished preovulatory serum estradiol (E2; P < 0.01) and LH ( P < 0.05) surge levels and reduced Kiss1 mRNA expression in the anteroventral periventricular nucleus ( P < 0.01) compared with controls. However, this reduced ovulatory LH response in intact ARKO females can be rescued by OVX and E2 priming or treatment with endogenous GnRH. These findings reveal that AR regulates the negative feedback response to E2, E2-positive feedback is compromised in ARKO mice, and AR-regulated negative and positive steroidal feedback pathways impact on intrahypothalamic control of the kisspeptin/GnRH/LH cascade. In addition, intraovarian AR-regulated pathways controlling antral to preovulatory follicle dynamics are disrupted because adult ARKO ovaries collected at proestrus have small antral follicles with reduced oocyte/follicle diameter ratios ( P < 0.01) and increased proportions of unhealthy large antral follicles ( P < 0.05) compared with controls. As a consequence of aberrant follicular growth patterns, proestrus ARKO ovaries also exhibit fewer preovulatory follicle ( P < 0.05) and corpora lutea numbers ( P < 0.01). However, embryo development to the blastocyst stage is unchanged in ARKO females, and hence, the subfertility is a consequence of reduced ovulations and not altered embryo quality. These findings reveal that the AR has a functional role in neuroendocrine regulation and timing of the ovulatory LH surge as well as antral/preovulatory follicle development.


2007 ◽  
Vol 19 (1) ◽  
pp. 288
Author(s):  
M.-K. Kim ◽  
H.-J. Oh ◽  
Y. H. Fibrianto ◽  
G. Jang ◽  
H.-J. Kim ◽  
...  

Growth, maturation, and ovulation of the Graafian follicle depend on appropriate patterns of secretion, sufficient concentrations, and adequate ratios of various reproductive hormones, especially follicle stimulating hormone (FSH) and luteinizing hormone (LH) (Van Tol et al. 1996 Mol. Reprod. Dev. 45, 218–224). The present study investigated the effects of FSH and human chorionic gonadotrophin (hCG) on the nuclear maturation of canine oocytes. In addition, in order to investigate the effect of stage of the estrous cycle on the meiotic competence of canine oocytes matured in vitro, oocytes were collected from various reproductive states and matured in vitro in the presence of the gonadotrophins. Estrous cycle stage was evaluated for each bitch by ovarian morphology, and bitches were categorized according to the stage of the estrous cycle (anestrus, follicular, or diestrus) prior to oocyte collection. Recovered oocytes were cultured in serum-free tissue culture medium (TCM)-199 supplemented with various concentrations of FSH (Exp. 1: 0, 0.1, 1.0, or 10 IU) or hCG (Exp. 2: 0, 0.5, 1.0, or 10 IU) or both (Exp. 3: 1 IU FSH + 1 IU hCG) for 72 h to determine the effective concentration of these hormones, and to examine their combined effect. After maturation culture, oocytes were denuded in PBS containing 0.1% (w/v) hyaluronidase by gentle pipetting. The denuded oocytes were stained with Hoechst 33342 in glycerol and the nuclear state of oocytes was evaluated under UV light. The rates of maturation to the MII stage were significantly higher (P &lt; 0.05) when follicular-stage oocytes were supplemented with 1 IU FSH (6.2%) compared with the other FSH-supplemented groups (0.0 to 3.3%) or to the control (1.8%), or 0.1 or 10.0 IU FSH (0 to 1.2%). Significantly higher (P &lt; 0.05) maturation rate to MII stage was observed in follicular-stage oocytes supplemented with 1.0 IU hCG (7.2%) compared with the control or other hCG-supplemented groups (0 to 1.5%). However, FSH and hCG together did not improve the nuclear maturation rate of canine oocytes (2.4%) compared with FSH (6.2%) and hCG alone (7.2%). In conclusion, FSH or hCG alone significantly increased the maturation of canine oocytes to the MII stage. This work was supported by grant No. M1062503005-06N250300510 from KOSEF, Republic of Korea.


2010 ◽  
Vol 22 (1) ◽  
pp. 360
Author(s):  
M. I. Cueto ◽  
F. Pereyra-Bonnet ◽  
P. Silvestre ◽  
A. E. Gibbons

The aim of the study was to assess possible variations in superovulatory yields due to different FSH treatments at 2 times of the year. Superovulation and embryo recovery were performed during the breeding (n = 63) andnonbreeding (n = 46) seasons in Merino ewes located at 41°S latitude. Animals were kept under the same conditions, housed outdoors in a sheltered and covered pen, and were fed a liveweight maintenance ration. All animals received 60-mg medroxyprogesterone acetate intravaginal sponges (Progespon®, Syntex, Buenos Aires, Argentina) for 14 days. Ewes were then randomly assigned to 2 different superovulatory treatments: classic (n = 74) and one shot (n = 35) in both seasons. Classic superovulatory treatment consisted of 7 decreasing doses (2 × 48 mg, 2 × 24 mg, 2 × 20 mg, and1 × 16 mg NIH-FSH-P1)ofFSH (Folltropin®-V, Bioniche, Belleville, Ontario, Canada), administered twice daily from 48 h before to 24 h after pessary removal. A dose of eCG (300 IU; Novormon®, Syntex) was administered at progestagen removal. One shot superovulatory treatment consisted of a single dose of FSH (70 mg NIH-FSH-P1) plus 300 UI of eCG injected at pessary withdrawal. Embryo donors were inseminated by laparoscopy with frozen-thawed semen (100 × 106 spz) 12 h after the onset of estrus. Surgical embryo recovery was done on Day 7 after sponge withdrawal and embryos were graded for quality according to morphology (Grade 1 = excellent or good; Grade 2 = fair; Grade 3 = poor; and Grade 4 = dead or degenerated; IETS 1998). A 2 × 2 factorial ANOVA was used to test the main effects (season and superovulatory treatment) and interactions. There were no significant differences in the proportion of responding ewes (>3 corpora lutea), ovulation rate, and recovered Grades 1 to 2 embryos between the breeding and nonbreeding season (Table 1; P > 0.05). However, number of recovered ova/embryos and ova/embryo recovery rate were higher during the breeding season compared with the nonbreeding season, whereas the percentage of nonfertilized ova was lower in the breeding season than in the nonbreeding season (P < 0.05). Analysis of data comparing superovulatory treatments showed that the proportion of responding ewes, ovulation rate, recovered embryos, and recovered Grades 1 to 2 embryos were lower for the one shot treatment than for the classic treatment (P < 0.05). Embryo recovery rate and nonfertilization rate did not differ between treatments (P > 0.05). It was concluded that there was an increase in the number of total recovered ova/embryos during the breeding season compared with the nonbreeding season, although the number of recovered good-quality embryos was not affected. The use of multiple FSH injections produced a higher number of total recovered and viable embryos in Merino sheep than the one shot superovulatory treatment. Table 1.Embryo yields in ewes submitted to superovulation


2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Tchoula Mamiafo Corinne ◽  
Pieme Constant Anatole ◽  
Ngogang Yonkeu Jeanne

Objective. Hormones play a vital role in initiating and maintaining male reproductive function. The present study explores the influence and predictive ability of two reproductive hormones on semen quality among men who were partners in an infertile couple. Design. During our cross sectional study, men were recruited from private and public hospital and laboratories for clinical evaluation of fertility status. Methods. Fresh semen samples were assessed for quality (concentration, motility and morphology) according to the 2010 World Health Organization manual and the serum levels of hormones, including follicle-stimulating hormone (FSH), Inhibin B was measured (ELISA). Results. We found a significant difference in the two groups regarding sperm concentration (p<0.0001), total sperm count (p<0.0001), progressive motility (p<0.0001), vitality (p<0.0001) and the percentage of normal forms (p=0.043). We found a strong and negative correlation between FSH and Inhibin B in the overall population, the normozoospermic reference group and the case group. Our study confirmed that Inhibin B was significantly and positively correlated with sperm concentration and leucocytes, and that FSH was negatively correlated to sperm concentration and vitality. Conclusion. Consistent with other studies, our results show strong association between semen quality and FSH and Inhibin B.


2016 ◽  
Vol 11 ◽  
pp. S31-S35 ◽  
Author(s):  
Mingsan Miao ◽  
Tan Wang ◽  
Yan Li ◽  
Min Li ◽  
Lin Guo ◽  
...  

The effect of Cynomorium flavonoids on mice model of perimenopausal depression was studied. Ovariectomized female mice (n=70) were randomly divided into 7 groups evenly and treated with different concentrations (5-400 mg/mL, of cynomorium flavonoids, gengnian'an capsule and soy isoflavones soft capsule. The model related groups were applied with different stress for consecutive 18 days. Behavior tests were performed on the 27th, 28th, and 29th days of administration. The concentrations of estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in serum as well as the 5-hydroxytryptamine (5-HT) and dopamine (DA) in brain homogenates were determined after the last administration. It was found that cynomorium flavonoids have significant effects on the mice with perimenopausal depression. 


1989 ◽  
Vol 67 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Richard F. Weick ◽  
Vaclav Pitelka ◽  
David L. Thompson

Experiments were performed to study the responsiveness of the pituitary to gonadotropin-releasing hormone (GnRH) during the dynamic changes in gonadotropin secretion associated with the estrogen-induced luteinizing hormone (LH) surge in the ovariectomized (OVX) rhesus monkey. Silastic capsules filled with estradiol-17-β were implanted subcutaneously in ovariectomized rhesus monkeys, resulting in an initial lowering of circulating LH and follicle-stimulating hormone (FSH) concentrations followed by an LH–FSH surge. GnRH was injected intravenously just before estrogen implantation, during the negative feedback response and during the rising, the peak, and the declining phases of the LH surge. The LH and FSH responses during the negative feedback phase were as large as those before estrogen treatment (control responses). During the rising phase of the LH surge, the acute response to GnRH injection did not differ significantly from the control response, but the responses 60 and 120 min after injection were somewhat increased. During the declining phase of the LH surge, the pituitary was not responsive to exogenous GnRH, although LH probably continued to be secreted at this time since the LH surge decreased more slowly than predicted by the normal rate of disappearance of LH in the monkey. We conclude that an increased duration of response to GnRH may be an important part of the mechanism by which estrogen induces the LH surge, but we do not see evidence of increased sensitivity of the pituitary to GnRH as an acute releasing factor at that time.Key words: LH surge, GnRH, FSH, ovariectomized monkey.


1977 ◽  
Vol 75 (1) ◽  
pp. 109-118 ◽  
Author(s):  
HILARY DOBSON ◽  
W. R. WARD

A radioimmunoassay system for the measurement of ovine follicle-stimulating hormone (FSH) was established. After the onset of normal oestrus, there were simultaneous surges of luteinizing hormone (LH) and FSH, and 24 h later, a surge of FSH alone. Administration of sodium pentobarbitone when the dual surge of LH and FSH was expected inhibited the release of LH, but prolonged that of FSH. Development of corpora lutea that took place immediately was normal in ewes treated with sodium pentobarbitone, but after the subsequent oestrus, the life-time of corpora lutea was abnormally short. When sodium pentobarbitone was administered at the time when the second surge of FSH was expected, no effect was observed on the level of LH or FSH. Subsequent development of corpora lutea was similar to that in the non-treated group. Administration of sodium pentobarbitone at the expected time of the dual surges of LH and FSH after infusion of oestradiol to anoestrous ewes blocked the release of both LH and FSH. Administration of sodium pentobarbitone at the expected time of the second surge of FSH after infusion of oestradiol delayed the increase in the level of FSH. In a pilot experiment after combined infusion of androstenedione and oestradiol, sodium pentobarbitone did not completely inhibit the release of FSH, but the release of LH was totally prevented.


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