Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction

Directory of Open Access Journals (Sweden)

Nawroth F

2015-04-01

Full Text Available Frank Nawroth,1 Andreas Tandler-Schneider,2 Wilma Bilger3 1Centre for Reproductive and Prenatal Medicine, Endocrinology and Osteology, Hamburg, Germany; 2Center for Reproductive Medicine, Fertility Center Berlin, Berlin, Germany; 3Medical Affairs, Fertility, Endocrinology and General Medicine, Merck Serono GmbH, Darmstadt, Germany (an affiliate of Merck KGaA, Darmstadt, Germany Abstract: This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles 15 mm. Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population. The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%, 50.0 IU (n=1,056 from N=3,189; 33.1%, and 75.0 IU (n=738 from N=3,189; 23.1% on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%, 50.0 IU (n=922 from N=3,189; 28.9%, and 75.0 IU (n=895 from N=3,189; 28.1% on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI. Keywords: ovulation

Comparative pharmacology of a new recombinant FSH expressed by a human cell line

DEFF Research Database (Denmark)

Koechling, Wolfgang; Plaksin, Daniel; Croston, Glenn E.

2017-01-01

Recombinant FSH proteins are important therapeutic agents for the treatment of infertility, including follitropin alfa expressed in Chinese Hamster Ovary (CHO) cells and, more recently, follitropin delta expressed in the human cell line PER.C6. These recombinant FSH proteins have distinct glycosy...

Preparation of 125I FSH hormone

International Nuclear Information System (INIS)

Castro de Sabbatini, D.; Nieto de Nunez, G.; Mitta, A.E.A.

1976-01-01

Labelling of human FSH of pituitary origin with 125 I and its purification are described. Suitable parameters are selected for the use of radioimmunologic technique for FSH dosage in human serum. (author) [es

Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH

DEFF Research Database (Denmark)

Main, Katharina M; Schmidt, Ida M; Toppari, Jorma

2002-01-01

BACKGROUND: Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period. OBJECTIVE: To investigate whether treating these patients with gonadotropins postna...... observed. CONCLUSIONS: Gonadotropin treatment in an infant with hypogonadotropic hypogonadism succeeded in inducing an increase in inhibin B and testicular growth.......BACKGROUND: Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period. OBJECTIVE: To investigate whether treating these patients with gonadotropins...... the normal range (0.05-0.17 IU/l and 79-112 pg/ml respectively). METHODS: From 7.9 to 13.7 months of age, the patient was treated with recombinant human LH and FSH in doses of 20 and 21.3 IU s.c. twice weekly respectively. RESULTS: During treatment concentrations of LH, FSH, inhibin B and estradiol increased...

Human fetal antehypophysis in vitro. Immunocytological study and radioimmunoassay of LH and FSH

International Nuclear Information System (INIS)

Li, J.Y.; Begeot, M.; Dubois, P.M.; Claustrat, B.

1977-01-01

Human fetal antehypophysis (16 males, 16 females and 4 unknown sex) were cultivated during several weeks. By immunocytochemistry LH gonadotroph cells were determined with anti-hTSH and anti-pLH serum. The release in vitro of LH and FSH was studied by radioimmunoassay. At the first medium change, the quantity of LH and FSH release was related to the gestational age and sex. A rapid decline of both LH and FSH occured over the 10 first days. There after, a basal release of LH was maintained during several months; the release of FSH was generally maintained at the lower limit of the assay. After 1 month in vitro, the level of LH could not be related to the sex. Release of LH was stimulated by synthetic LRF. A significant increase was observed independently of the sex and age of the fetuses studied [fr

Differential gene expression in human granulosa cells from recombinant FSH versus human menopausal gonadotropin ovarian stimulation protocols

Directory of Open Access Journals (Sweden)

Bietz Mandi G

2010-03-01

Full Text Available Abstract Background The study was designed to test the hypothesis that granulosa cell (GC gene expression response differs between recombinant FSH and human menopausal gonadotropin (hMG stimulation regimens. Methods Females Results After exclusions, 1736 genes exhibited differential expression between groups. Over 400 were categorized as signal transduction genes, ~180 as transcriptional regulators, and ~175 as enzymes/metabolic genes. Expression of selected genes was confirmed by RT-PCR. Differentially expressed genes included A kinase anchor protein 11 (AKAP11, bone morphogenetic protein receptor II (BMPR2, epidermal growth factor (EGF, insulin-like growth factor binding protein (IGFBP-4, IGFBP-5, and hypoxia-inducible factor (HIF-1 alpha. Conclusions Results suggest that major differences exist in the mechanism by which pure FSH alone versus FSH/LH regulate gene expression in preovulatory GC that could impact oocyte maturity and developmental competence.

Follicle-stimulating hormone (FSH) activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

Science.gov (United States)

Piketty, Vincent; Kara, Elodie; Guillou, Florian; Reiter, Eric; Crepieux, Pascale

2006-01-01

Background The follicle-stimulating hormone receptor (FSH-R) is a seven transmembrane spanning receptor (7TMR) which plays a crucial role in male and female reproduction. Upon FSH stimulation, the FSH-R activates the extracellular signal-regulated kinases (ERK). However, the mechanisms whereby the agonist-stimulated FSH-R activates ERK are poorly understood. In order to activate ERK, some 7 TMRs require beta-arrestin-and dynamin-dependent internalization to occur, whereas some others do not. In the present study, we examined the ability of the FSH-activated FSH-R to induce ERK phosphorylation, in conditions where its beta-arrestin- and dynamin-mediated internalization was impaired. Methods Human embryonic kidney (HEK) 293 cells were transiently transfected with the rat FSH-R. Internalization of the FSH-R was manipulated by co-expression of either a beta-arrestin (319–418) dominant negative peptide, either an inactive dynamin K44A mutant or of wild-type beta-arrestin 1 or 2. The outcomes on the FSH-R internalization were assayed by measuring 125I-FSH binding at the cell surface when compared to internalized 125I-FSH binding. The resulting ERK phosphorylation level was visualized by Western blot analysis. Results In HEK 293 cells, FSH stimulated ERK phosphorylation in a dose-dependent manner. Co-transfection of the beta- arrestin (319–418) construct, or of the dynamin K44A mutant reduced FSH-R internalization in response to FSH, without affecting ERK phosphorylation. Likewise, overexpression of wild-type beta-arrestin 1 or 2 significantly increased the FSH-R internalization level in response to FSH, without altering FSH-induced ERK phosphorylation. Conclusion From these results, we conclude that the FSH-R does not require beta-arrestin- nor dynamin-mediated internalization to initiate ERK phosphorylation in response to FSH. PMID:16787538

Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

Energy Technology Data Exchange (ETDEWEB)

Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. (Department of Biochemistry, Albany Medical College, New York, NY (USA))

1991-06-01

We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

Mixed protocols: Multiple ratios of FSH and LH bioactivity using highly purified, human-derived FSH (BRAVELLE and highly purified hMG (MENOPUR are unaltered by mixing together in the same syringe

Directory of Open Access Journals (Sweden)

Raike Elizabeth

2005-11-01

Full Text Available Abstract Background The use of mixed or blended protocols, that utilize both FSH and hMG, for controlled ovarian hyperstimulation is increasing in use. To reduce the number of injections a patient must administer, many physicians instruct their patients to mix their FSH and hMG together to be given as a single injection. Therefore, the goal of this study was to definitively determine if the FSH and LH bioactivities of highly purified, human-derived FSH (Bravelle(R and highly purified hMG (Menopur(R were altered by reconstituting in 0.9% saline and mixing in the same syringe. Methods Bravelle(R and Menopur(R were reconstituted in 0.9% saline and mixed in a Becton Dickinson plastic syringe. The FSH and LH bioactivities of the products were determined after injecting female and male rats, respectively, with Bravelle(R, Menopur(R, or a mixture of Bravelle(R and Menopur(R. Ratios of FSH:LH activity tested were 150:75 IU (1 vial Bravelle(R: 1 vial Menopur(R, 300:75 IU (3 vials Bravelle(R: 1 vial Menopur(R or 300:225 IU (1 vial Bravelle(R: 3 vials of Menopur(R. Results There were no statistically significant changes in either FSH or LH bioactivity that occurred after mixing Bravelle(R with Menopur(R in the same syringe. The theoretical vs. actual FSH bioactivity for Bravelle(R and Menopur(R were 75 vs. 76.58 IU/mL and 75 vs. 76.0 IU/mL, respectively. For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle(R: 1 vial Menopur(R, 300:75 IU (3 vials Bravelle(R: 1 vial Menopur(R or 300:225 IU (1 vial Bravelle(R: 3 vials of Menopur(R tested, the theoretical vs. actual FSH bioactivities were 150 vs. 156.86 IU/mL, 300 vs. 308.69 IU/mL and 300 vs. 306.58 IU/mL, respectively. The theoretical vs. actual LH bioactivity for Menopur(R in the above mentioned ratios tested were 75 vs. 77.50 IU/mL. For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle(R: 1 vial Menopur(R, 300:75 IU (3 vials Bravelle(R: 1 vial Menopur(R or 300:225 IU (1

Allosteric activation of the follicle-stimulating hormone (FSH) receptor by selective, nonpeptide agonists.

Science.gov (United States)

Yanofsky, Stephen D; Shen, Emily S; Holden, Frank; Whitehorn, Erik; Aguilar, Barbara; Tate, Emily; Holmes, Christopher P; Scheuerman, Randall; MacLean, Derek; Wu, May M; Frail, Donald E; López, Francisco J; Winneker, Richard; Arey, Brian J; Barrett, Ronald W

2006-05-12

The pituitary glycoprotein hormones, luteinizing hormone and follicle-stimulating hormone (FSH), act through their cognate receptors to initiate a series of coordinated physiological events that results in germ cell maturation. Given the importance of FSH in regulating folliculogenesis and fertility, the development of FSH mimetics has been sought to treat infertility. Currently, purified and recombinant human FSH are the only FSH receptor (FSH-R) agonists available for infertility treatment. By screening unbiased combinatorial chemistry libraries, using a cAMP-responsive luciferase reporter assay, we discovered thiazolidinone agonists (EC50's = 20 microm) of the human FSH-R. Subsequent analog library screening and parallel synthesis optimization resulted in the identification of a potent agonist (EC50 = 2 nm) with full efficacy compared with FSH that was FSH-R-selective and -dependent. The compound mediated progesterone production in Y1 cells transfected with the human FSH-R (EC50 = 980 nm) and estradiol production from primary rat ovarian granulosa cells (EC50 = 10.5 nm). This and related compounds did not compete with FSH for binding to the FSH-R. Use of human FSH/thyroid-stimulating hormone (TSH) receptor chimeras suggested a novel mechanism for receptor activation through a binding site independent of the natural hormone binding site. This study is the first report of a high affinity small molecule agonist that activates a glycoprotein hormone receptor through an allosteric mechanism. The small molecule FSH receptor agonists described here could lead to an oral alternative to the current parenteral FSH treatments used clinically to induce ovarian stimulation for both in vivo and in vitro fertilization therapy.

Efficacy of Highly Purified Urinary FSH versus Recombinant FSH in Chinese Women over 37 Years Undergoing Assisted Reproductive Techniques

Directory of Open Access Journals (Sweden)

Xuemei Liu

2015-02-01

Full Text Available Background: Urine derived follicle-stimulating hormone (uFSH contains a higher proportion of acidic isoforms, whereas recombinant FSH (rFSH contains a higher proportion of less-acidic isoforms. Less-acidic isoforms have a faster clearance, and thus a shorter half-life than the acidic FSH isoforms. The slow clearance of the acidic isoforms has a longer half-life and higher biological activity. This study was designed to determine whether uFSH or rFSH is more effective in older Chinese women undergoing assisted reproductive techniques (ART. Materials and Methods: This is a prospective, randomized, controlled cohort study. A total of 508 Chinese women over 37 years were randomized into two following study groups for their in vitro fertilization (IVF or intracytoplasmic sperm injection (ICSI cycles: i. group A (n=254 were treated with rFSH, and ii. group B (n=254 were treated with uFSH. Both groups were suppressed with a gonadotropin-releasing hormone (GnRH analogue using a long down-regulation protocol. The main outcomes for comparison were days of stimulation, estradiol (E2 on the day of human chorionic gonadotropin (hCG administration, number of oocytes collected, amount of FSH used, quantity of FSH/oocyte, endometrial thickness at hCG day, M П oocyte rate, 2PN zygote rate, grade І embryo rate, number of embryos cryopreserved, pregnancy rate, implantation rate, abortion rate and the rate of no transferable embryos. Results: Twenty two cycles including 16 cycles with poor ovarian response and six cycles with ovarian hyperstimulation syndrome were cancelled. There were 243 cycles left in each group. The patients treated with uFSH had a significantly higher 2PN zygote rate (87.4 vs. 76.6%, p0.05. Conclusion: This study showed that uFSH produced a significantly higher proportion of grade І embryos than rFSH in older Chinese women and there was a significantly lower chance of no transferable embryos in uFSH cycles. The clinical efficacy of the two

In-vivo biological activity and glycosylation analysis of a biosimilar recombinant human follicle-stimulating hormone product (Bemfola compared with its reference medicinal product (GONAL-f.

Directory of Open Access Journals (Sweden)

Renato Mastrangeli

Full Text Available Recombinant human follicle-stimulating hormone (r-hFSH is widely used in fertility treatment. Although biosimilar versions of r-hFSH (follitropin alfa are currently on the market, given their structural complexity and manufacturing process, it is important to thoroughly evaluate them in comparison with the reference product. This evaluation should focus on how they differ (e.g., active component molecular characteristics, impurities and potency, as this could be associated with clinical outcome. This study compared the site-specific glycosylation profile and batch-to-batch variability of the in-vivo bioactivity of Bemfola, a biosimilar follitropin alfa, with its reference medicinal product GONAL-f. The focus of this analysis was the site-specific glycosylation at asparagine (Asn 52 of the α-subunit of FSH, owing to the pivotal role of Asn52 glycosylation in FSH receptor (FSHR activation/signalling. Overall, Bemfola had bulkier glycan structures and greater sialylation than GONAL-f. The nominal specific activity for both Bemfola and GONAL-f is 13,636 IU/mg. Taking into account both the determined potency and the nominal amount the average specific activity of Bemfola was 14,522 IU/mg (105.6% of the nominal value, which was greater than the average specific activity observed for GONAL-f (13,159 IU/mg; 97.3% of the nominal value; p = 0.0048, although this was within the range stated in the product label. A higher batch-to-batch variability was also observed for Bemfola versus GONAL-f (coefficient of variation: 8.3% vs 5.8%. A different glycan profile was observed at Asn52 in Bemfola compared with GONAL-f (a lower proportion of bi-antennary structures [~53% vs ~77%], and a higher proportion of tri-antennary [~41% vs ~23%] and tetra-antennary structures [~5% vs <1%]. These differences in the Asn52 glycan profile might potentially lead to differences in FSHR activation. This, together with the greater bioactivity and higher batch-to-batch variability

Interactions between androgens, FSH, anti-Müllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary.

Science.gov (United States)

Dewailly, Didier; Robin, Geoffroy; Peigne, Maëliss; Decanter, Christine; Pigny, Pascal; Catteau-Jonard, Sophie

2016-11-01

Androgens, FSH, anti-Müllerian hormone (AMH) and estradiol (E2) are essential in human ovarian folliculogenesis. However, the interactions between these four players is not fully understood. The purpose of this review is to highlight the chronological sequence of the appearance and function of androgens, FSH, AMH and E2 and to discuss controversies in the relationship between FSH and AMH. A better understanding of this interaction could supplement our current knowledge about the pathophysiology of the polycystic ovary syndrome (PCOS). A literature review was performed using the following search terms: androgens, FSH, FSH receptor, anti-Mullerian hormone, AMHRII, estradiol, follicle, ovary, PCOS, aromatase, granulosa cell, oocyte. The time period searched was 1980-2015 and the databases interrogated were PubMed and Web of Science. During the pre-antral ('gonadotropin-independent') follicle growth, FSH is already active and promotes follicle growth in synergy with theca cell-derived androgens. Conversely, AMH is inhibitory by counteracting FSH. We challenge the hypothesis that AMH is regulated by androgens and propose rather an indirect effect through an androgen-dependent amplification of FSH action on granulosa cells (GCs) from small growing follicles. This hypothesis implies that FSH stimulates AMH expression. During the antral ('gonadotropin-dependent') follicle growth, E2 production results from FSH-dependent activation of aromatase. Conversely, AMH is inhibitory but the decline of its expression, amplified by E2, allows full expression of aromatase, characteristic of the large antral follicles. We propose a theoretical scheme made up of two triangles that follow each other chronologically. In PCOS, pre-antral follicle growth is excessive (triangle 1) because of intrinsic androgen excess that renders GCs hypersensitive to FSH, with consequently excessive AMH expression. Antral follicle growth and differentiation are disturbed (triangle 2) because of the

Patient evaluation of the use of follitropin alfa in a prefilled ready-to-use injection pen in assisted reproductive technology: an observational study

Directory of Open Access Journals (Sweden)

Welcker J

2010-09-01

Full Text Available Abstract Background Self-administration of recombinant human follicle-stimulating hormone (r-hFSH can be performed using injection pen devices by women undergoing assisted reproductive technology procedures. The objective of this study was to explore the use of the prefilled follitropin alfa pen in routine assisted reproductive technology procedures in Germany. Methods This prospective, observational study was conducted across 43 German IVF centres over a period of 1.75 years. Patients who had used the prefilled follitropin alfa pen in the current or a previous cycle of controlled ovarian stimulation completed a questionnaire to assess their opinions of the device. Results A total of 5328 patients were included in the study. Of these, 2888 reported that they had previous experience of daily FSH injections. Significantly more patients reported that less training was required to use the prefilled follitropin alfa pen than a syringe and lyophilized powder (1997/3081 [64.8%]; p Conclusions In this questionnaire-based survey, routine use of the prefilled follitropin alfa pen was well accepted and associated with favourable patient perceptions. Users of the pen found it easier to initially learn how to use, and subsequently use, than other injection methods. In general, the prefilled follitropin alfa pen was the preferred method for self-administration of gonadotrophins. Together with previous findings, the results here indicate a high level of patient satisfaction among users of the prefilled follitropin alfa pen for daily self-administration of r-hFSH.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

Science.gov (United States)

Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

The Immunoexpression of FSH-R in the Ductuli Efferentes and the Epididymis of Men and Rat: Effect of FSH on the Morphology and Steroidogenic Activity of Rat Epididymal Epithelial Cells In Vitro

Directory of Open Access Journals (Sweden)

Małgorzata Świder-Al-Amawi

2010-01-01

Full Text Available The Sertoli cells were regarded as the only target for FSH in male reproductive system. The expression of FSH receptor (FSH-R was detected also in epithelial cells of the caput epididymis of rat and monkey. We showed in the immunohistochemistry study the expression of FSH-R in rat and human ductuli efferentes and the caput, corpus, and cauda epididymis, moreover, by Western blot analysis in the caput and cauda epididymis of rat. Additionally, we presented that the morphology of rat epididymal epithelial cells in vitro was affected by FSH, and FSH stimulation resulted in the increase of 17β-estradiol synthesis by rat caput epididymal cells in dose-depended manner. In conclusion, the identification of FSH receptors in human and rat epididymides supports our results that the epididymis is a target organ not only for LH but additionally for FSH. On the basis of the results we showed for the first time that morphology of epididymal epithelial cells and epididymal steroidogenesis can be regulated by FSH.

Highly purified HMG versus recombinant FSH for ovarian stimulation in IVF cycles

DEFF Research Database (Denmark)

Platteau, P.; Nyboe, Andersen A.; Loft, A.

2008-01-01

The objective of this study was to compare the live birth rates resulting from ovarian stimulation with highly purified human menopausal gonadotrophin (HP-HMG), which combines FSH and human chorionic gonadotrophin-driven LH activities, or recombinant FSH (rFSH) alone in women undergoing IVF cycles....... An integrated analysis was performed of the raw data from two randomized controlled trials that were highly comparable in terms of eligibility criteria and post-randomization treatment regimens with either HP-HMG or rFSH for ovarian stimulation in IVF, following a long down-regulation protocol. All randomized...... subjects who received at least one dose of gonadotrophin in an IVF cycle (HP-HMG, n = 491; rFSH, n = 495) were included in the analysis. Subjects who underwent intracytoplasmic sperm injection cycles were excluded. The superiority of one gonadotrophin preparation over the other was tested using...

Recombinant FSH versus urinary gonadotrophins or recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome

NARCIS (Netherlands)

Bayram, N.; van Wely, M.; van der Veen, F.

2001-01-01

BACKGROUND: Over the last four decades, various urinary FSH (uFSH) products of different purity have been developed. In 1988 recombinant FSH (rFSH ) was prepared by transfecting Chinese hamster ovary cell lines with both FSH subunit genes. Both rFSH and uFSH are known to be effective in inducing

Heterologous radioimmunoassays for monkey gonadotrophins. I. Assessment of the reagents proposed for the assay of FSH

Energy Technology Data Exchange (ETDEWEB)

Khan, S A; Diczfalusy, E [Reproductive Endocrinology Research Unit, Karolinska sjukhuset, Stockholm

1983-01-01

The reliability of the reagents used in heterologous immunoassay procedures for FSH in monkey sera was assessed. Re-investigation of the iodination and purification of the human FSH tracer confirmed the presence of different iodinated molecular species, such as a high molecular weight aggregated material, 'intact' human FSH and subunits. Tracers obtained with the chloramine T procedure were superior to those obtained by the lactoperoxidase method. Purification by cellulose adsorption chromatography resulted in partial dissociation of the intact hormone into free subunits, while Sephadex G-25 chromatography did not yield any subunit-like material. Purification by Ultrogel AcA 54 gave the best separation of the 'intact' iodinated FSH. Binding studies indicated that an anti-ovine FSH (oFSH) serum showed a high degree of binding to 'intact' hFSH, although its binding to subunits and to aggregated material was also significant. The highest degree of binding to this antiserum was shown by the 'intact' tracer iodinated with chloramine T and purified sequentially by Sephadex G-25 and Ultrogel (AcA 54) chromatography. Using a highly purified hFSH tracer in combination with three antisera (anti-oFSH, H 31; anti-hFSH, WHO, M-93-2; anti-hFSH, NIH, batch No. 5) displacement curves were investigated with three purified monkey FSH preparations. No displacement was observed with a widely available anti-hFSH (WHO, M 93-2) serum. However, linear dose dependent displacement was found with another anti-hFSH (NIH, batch No. 5) serum and with an anti-oFSH (H 31) serum. Comparison of immunoassay with the human and ovine antiserum revealed significant differences in slope, parallelism, precision and effective range. Significant discrepancies in the FSH potency estimates in monkey sera were also observed with the two assay systems. It is suggested that - until a homologous system is developed - the immunoassay employing an hFSH tracer and an anti-oFSH serum should be used for macaque FSH.

Characterisation of Population Pharmacokinetics and Endogenous Follicle Stimulating Hormone (FSH) Levels after Multiple Dosing of a Recombinant Human FSH, FE 999049, in Healthy Women

DEFF Research Database (Denmark)

Rose, Trine Høyer; Röshammer, Daniel; Erichsen, Lars

2016-01-01

: Longitudinal measurements of FSH, luteinising hormone, progesterone, estradiol, and inhibin B levels were collected after repeated subcutaneous dosing with 225 IU of FE 999049 in 24 gonadotropin downregulated healthy women. The FSH data were described using nonlinear mixed-effects modelling. Results...... increased with body weight in accordance with an allometrically scaled power exponent of 0.75 and 1, respectively. Endogenous FSH levels were lower in individuals with higher progesterone levels at baseline and were further suppressed over time with increasing inhibin B levels. Conclusions......: This characterisation of FE 999049 population pharmacokinetics after repeated dosing is in line with previous findings after single-dose administration. The results provide a basis for study design and data evaluation in the future development of recombinant FSH products, and show it can be of importance to account...

Effects of human chorionic gonadotropin combined with clomiphene on Serum E2, FSH, LH and PRL levels in patients with polycystic ovarian syndrome.

Science.gov (United States)

Yonggang, Huang; Xiaosheng, Lu; Zhaoxia, Huang; Yilu, Chen; Jiqiang, Lv; Huina, Zhang

2017-02-01

Effects of human chorionic gonadotropin combined with clomiphene on serum E 2 , FSH, LH and PRL levels in patients with polycystic ovarian syndrome were analyzed. 90 patients with polycystic ovarian syndrome treated from January 2015 to March 2016 were randomly and evenly divided into control group and observation group. Patients in the control group were only treated with clomiphene. On the basis of the treatment in control group, human chorionic gonadotropin was added in the treatment of observation group. The changes of E 2 , FSH, LH, PRL levels were compared between two groups before and after the treatment. Clinical curative effects of patients in the two groups was evaluated. Adverse reactions during treatment in two groups were observed and recorded. The incidence of adverse reactions was calculated. Serum E 2 , FSH, LH and PRL levels in the two groups decreased significantly after treatment compared with that before treatment. The difference is statistical significant ( P   0.05). Combined use of human chorionic gonadotropin can significantly reduce serum E 2 , FSH, LH and PRL levels, improve clinical curative effects and reduce the incidence of adverse reactions. Human chorionic gonadotropin has high application value on the treatment of polycystic ovary syndrome.

Follicle-stimulating hormone (FSH) blood test

Science.gov (United States)

... ency/article/003710.htm Follicle-stimulating hormone (FSH) blood test To use the sharing features on this page, please enable JavaScript. The follicle stimulating hormone (FSH) blood test measures the level of FSH in blood. FSH ...

Physico-chemical characterization of human recombinant follicle-stimulating hormone (hFSH) and its subunits by reversed-phase high-performance liquid chromatography ( RP-HPLC): comparison with pituitary hFSH reference preparation from 'National Hormone and Pituitary Program' from USA; Caracterizacao fisico-quimica da foliculotropina humana(hFSH) recombinabte e de suas subunidades, por cromatografia liquida de alta eficiencia (HPLC) em fase reversa: comparacao com a preparacao de referencia de hFSH de origem hipofisaria do ''National Hormone and Pituitary Program'' dos EUA

Energy Technology Data Exchange (ETDEWEB)

Loureiro, Renan Fernandes

2006-07-01

A reversed-phase high-performance liquid chromatography (RP-HPLC) method for the qualitative and quantitative analysis of intact human folliclestimulating hormone (hFSH) was established and validated for accuracy, precision and sensitivity. Human FSH is a dimeric glycoprotein hormone widely used as a diagnostic analyte and as therapeutic product in reproductive medicine. The technique developed preserves the protein integrity, allowing the analysis of the intact heterodimeric form rather than just of its subunits, as it is the case for the majority of the conditions currently employed. This methodology has also been employed for comparing the relative hydrophobicity of pituitary, urinary and two Chinese hamster ovary (CHO)-derived hFSH preparations, as well as of two other related glycoprotein hormones of the anterior pituitary: human thyroid-stimulating hormone (hTSH) and human luteinizing hormone (hLH). The least hydrophobic of the three glycohormones analyzed was hFSH, followed by hTSH and hLH. A significant difference (p<0.005) was observed in t{sub R} between the pituitary and recombinant hFSH preparations, reflecting structural differences in their carbohydrate moieties. Two main isoforms were detected in urinary hFSH, including a form which was significantly different (p<0.005) for the pituitary and recombinant preparations. The linearity of the dose-response curve (r = 0.9965, n = 15) for this RP-HPLC methodology, as well as an inter-assay precision with relative standard deviation less than 4% for the quantification of different hFSH preparations and a sensitivity of the order of 40 ng, were demonstrated. The chromatographic behavior and relative hydrophobicity of the individual subunits of the pituitary and recombinant preparations were also analyzed. Furthermore, the accurate molecular mass of the individual hFSH subunits and of the heterodimer were simultaneously determined by matrix-assisted laser desorption ionization time-of-flight mass spectral

Lower sperm DNA fragmentation after r-FSH administration in functional hypogonadotropic hypogonadism.

Science.gov (United States)

Ruvolo, Giovanni; Roccheri, Maria Carmela; Brucculeri, Anna Maria; Longobardi, Salvatore; Cittadini, Ettore; Bosco, Liana

2013-04-01

An observational clinical and molecular study was designed to evaluate the effects of the administration of recombinant human FSH on sperm DNA fragmentation in men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In the study were included 53 men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In all patients, sperm DNA fragmentation index (DFI), assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) in situ DNA nick end-labelling (TUNEL) assay, was evaluated before starting the treatment with 150 IU of recombinant human FSH, given three times a week for at least 3 months. Patients' semen analysis and DNA fragmentation index were re-evaluated after the 3-month treatment period. After recombinant human FSH therapy, we did not find any differences in terms of sperm count, motility and morphology. The average DNA fragmentation index was significantly reduced (21.15 vs 15.2, p15 %), while no significant variation occurred in the patients with DFI values ≤ 15 %. Recombinant human FSH administration improves sperm DNA integrity in hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia men with DNA fragmentation index value >15 % .

Mutations and polymorphisms in FSH receptor: functional implications in human reproduction.

Science.gov (United States)

Desai, Swapna S; Roy, Binita Sur; Mahale, Smita D

2013-12-01

FSH brings about its physiological actions by activating a specific receptor located on target cells. Normal functioning of the FSH receptor (FSHR) is crucial for follicular development and estradiol production in females and for the regulation of Sertoli cell function and spermatogenesis in males. In the last two decades, the number of inactivating and activating mutations, single nucleotide polymorphisms, and spliced variants of FSHR gene has been identified in selected infertile cases. Information on genotype-phenotype correlation and in vitro functional characterization of the mutants has helped in understanding the possible genetic cause for female infertility in affected individuals. The information is also being used to dissect various extracellular and intracellular events involved in hormone-receptor interaction by studying the differences in the properties of the mutant receptor when compared with WT receptor. Studies on polymorphisms in the FSHR gene have shown variability in clinical outcome among women treated with FSH. These observations are being explored to develop molecular markers to predict the optimum dose of FSH required for controlled ovarian hyperstimulation. Pharmacogenetics is an emerging field in this area that aims at designing individual treatment protocols for reproductive abnormalities based on FSHR gene polymorphisms. The present review discusses the current knowledge of various genetic alterations in FSHR and their impact on receptor function in the female reproductive system.

Gonadotropin determination in 24-h-urine by sensitive LH and FSH radioimmunoassays

International Nuclear Information System (INIS)

Raid, A.; Fenske, M.; Koenig, A.

1979-01-01

Urinary lutropin (LH) and follitropin (FSH) were precipitated with acetone and measured by specific radioimmunoassays. Recovery experiments with special regard to urinary pH values were done by adding 125 I-labelled LH and FSH to unprocessed urine. At pH 4.5 68.6% of LH and 66.1% of FSH were recovered. Increasing pH values up to 6.0 resulted in a significant recovery loss of 125 I-LH, but not of 125 I-FSH. Immunoreactive FSH concentrations decreased significantly 6 and 48 hours after starting storage at room temperature. In healthy males and females there were found mean LH and FSH concentrations in 24-h-urine which were similar to those reported by others: LH: males: 22.6 IU; cycling females: 17.8 IU; postmenopausal females: 49.1 IU; FSH: males 6.0 IU; cycling females: 15.0 IU; postmenopausal females: 48.5 IU. Because of their high sensitivity and practicability. These radioimmunoassays could be clinically useful approaches in assessment of pituitary and gonadal disorders in human subjects. (author)

Follicle-stimulating hormone (FSH) unmasks specific high affinity FSH-binding sites in cell-free membrane preparations of porcine granulosa cells

Energy Technology Data Exchange (ETDEWEB)

Ford, K.A.; LaBarbera, A.R.

1988-11-01

The purpose of these studies was to determine whether changes in FSH receptors correlated with FSH-induced attenuation of FSH-responsive adenylyl cyclase in immature porcine granulosa cells. Cells were incubated with FSH (1-1000 ng/ml) for up to 24 h, treated with acidified medium (pH 3.5) to remove FSH bound to cells, and incubated with (125I)iodo-porcine FSH to quantify FSH-binding sites. FSH increased binding of FSH in a time-, temperature-, and FSH concentration-dependent manner. FSH (200 ng/ml) increased binding approximately 4-fold within 16 h. Analysis of equilibrium saturation binding data indicated that the increase in binding sites reflected a 2.3-fold increase in receptor number and a 5.4-fold increase in apparent affinity. The increase in binding did not appear to be due to 1) a decrease in receptor turnover, since the basal rate of turnover appeared to be very slow; 2) an increase in receptor synthesis, since agents that inhibit protein synthesis and glycosylation did not block the increase in binding; or 3) an increase in intracellular receptors, since agents that inhibit cytoskeletal components had no effect. Agents that increase intracellular cAMP did not affect FSH binding. The increase in binding appeared to result from unmasking of cryptic FSH-binding sites, since FSH increased binding in cell-free membrane preparations to the same extent as in cells. Unmasking of cryptic sites was hormone specific, and the sites bound FSH specifically. Unmasking of sites was reversible in a time- and temperature-dependent manner after removal of bound FSH. The similarity between the FSH dose-response relationships for unmasking of FSH-binding sites and attenuation of FSH-responsive cAMP production suggests that the two processes are functionally linked.

Both recombinant African catfish LH and FSH are able to activate the African catfish FSH receptor

NARCIS (Netherlands)

Vischer, HF; Granneman, JCM; Linskens, MHK; Schulz, RW; Bogerd, J

LH and FSH are heterodimeric glycoprotein hormones, composed of a common alpha-subunit non-covalently associated with a hormone-specific beta-subunit. Repeated efforts to isolate catfish FSH (cfFSH) have not been successful and only catfish LH (cfLH) has been purified from catfish pituitaries.

Controlled ovarian stimulation with r-FSH plus r-LH vs. HMG plus r-FSH in patients candidate for IVF/ICSI cycles: An RCT

Directory of Open Access Journals (Sweden)

Ensieh Shahrokh Tehraninejad

2017-08-01

Full Text Available Background: Different combination of gonadotropin preparation has been introduced with no definite superiority of one over others in in vitro fertilization (IVF, but individualized regimens for each patient are needed. Objective: The aim of the present study was to investigate the effect of controlled ovarian stimulation with recombinant- follicle stimulating hormone (r-FSH plus recombinant-luteinizing hormone (rLH versus human menopausal gonadotropin (HMG plus r-FSH on fertility outcomes in IVF patients. Materials and Methods: This is a randomized clinical trial study that was performed from October 2014-April 2016 on 140 infertile patients with a set of inclusion criteria that referred to infertility clinics in Vali- asr and Gandhi Hospital in Tehran. The women were randomly divided into two treatment groups. The first group (n=70 received rFSH from the second day of cycle and was added HMG in 6th day and the 2nd group (n=70, received rFSH from the second day of cycle and was added recombinant-LH in 6th day. Then ovum Pick-Up and embryo transfer were performed. In this study, we assessed the outcomes such as; chemical and clinical pregnancy rate, live birth and abortion rate. Results: Number of follicles in ovaries, total number of oocytes or M2 oocytes and quality of fetuses has no significant differences between two groups (p>0.05. Total number of fetuses were significantly higher in patients who received rFSH + HMG (p=0.02. Fertility outcomes consisted of: live birth rate, chemical pregnancy and clinical pregnancy rate were higher in rFSH + HMG group in comparison to rFSH +r-LH group (p<0.05. Conclusion: It seems that in IVF patients, HMG + rFSH used for controlled ovarian hyperstimulation have better effects on fertility outcomes, but in order to verify the results, it is recommended to implement studies on more patients.

Preparation of high-quality iodine-125-labelled pituitary human follicle-stimulating hormone (hFSH) for radioimmunoassay

International Nuclear Information System (INIS)

Pinto, H.; Lerario, A.C.; Toledo e Souza, I.T. de; Wajchenberg, B.L.; Mattar, E.; Pieroni, R.R.

1977-01-01

A method is described for the enzymatic radioiodination of human follice-stimulating hormone (hFSH) by a system consisting of lactoperoxidase, hydrogen peroxide and Na 125 I. It is compared with the chloramine-T modified technique. A satisfactory specific activity of the labelled hormone is obtained with the enzymatic iodination, with much greater immunoreactivity and stability than with chloramine-T [pt

A FSH-Secreting Pituitary Macroadenoma Causing A Testosterone Deficiency Syndrome

Directory of Open Access Journals (Sweden)

Xiong Wang

2014-03-01

Full Text Available FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T and estradiol (E2 levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG tests. Both follicle stimulating hormone (FSH and luteinizing hormone (LH showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man’s sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis.

A cost per live birth comparison of HMG and rFSH randomized trials.

Science.gov (United States)

Connolly, Mark; De Vrieze, Kathleen; Ombelet, Willem; Schneider, Dirk; Currie, Craig

2008-12-01

To help inform healthcare treatment practices and funding decisions, an economic evaluation was conducted to compare the two leading gonadotrophins used for IVF in Belgium. Based on the results of a recently published meta-analysis, a simulated decision tree model was constructed with four states: (i) fresh cycle, (ii) cryopreserved cycle, (iii) live birth and (iv) treatment withdrawal. Gonadotrophin costs were based on highly purified human menopausal gonadotrophin (HP-HMG; Menopur) and recombinant FSH (rFSH) alpha (Gonal-F). After one fresh and one cryopreserved cycle the average treatment cost with HP-HMG was lower than with rFSH (HP-HMG euro3635; rFSH euro4103). The average cost saving per person started on HP-HMG when compared with rFSH was euro468. Additionally, the average costs per live birth of HP-HMG and rFSH were found to be significantly different: HP-HMG euro9996; rFSH euro13,009 (P cost-saving even after key parameters in the model were varied in the probabilistic sensitivity analysis. Treatment with HP-HMG was found to be the dominant treatment strategy in IVF because of improved live birth rates and lower costs. Within a fixed healthcare budget, the cost-savings achieved using HP-HMG would allow for the delivery of additional IVF cycles.

Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

International Nuclear Information System (INIS)

Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

1984-01-01

Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with 125 I-lipoproteins [human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)]. The media were then analyzed for lipoprotein protein coat degradation products (mainly 125 I-monoiodotyrosine) and progestin [mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)]. In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production

Gonadotropin Regulation of Retinoic Acid Activity in the Testis

Directory of Open Access Journals (Sweden)

Seyedmehdi Nourashrafeddin

2018-02-01

Full Text Available Initiation of spermatogenesis in primates is triggered at puberty by an increase in gonadotropins; i.e., follicle-stimulating hormone (FSH and luteinizing hormone (LH. Prior to puberty, testis of the monkey contains only undifferentiated germ cells. However, sermatogonial differentiation and spermatogenesis may be initiated prior to puberty after stimulation with exogenous LH and FSH. Retinoic acid (RA signaling is considered to be a major component that drives spermatogonial differentiation. We were interested in evaluating the relative role of LH and FSH, either alone or in combination, in regulating the retinoic acid signaling in monkey testis. Sixteen juvenile male rhesus monkeys (Macaca mulatta were infused with intermittent recombinant single chain human LH (schLH or recombinant human FSH (rhFSH or a combination of both for 11 days. We then analyzed the expression of the several putative RA signaling pathway related genes; i.e. RDH10, RDH11, ALDH1A1, ALDH1A2, CYP26B1, CRABP1, CRABP2, STRA6, STRA8 in the testis after 11 days of stimulation with vehicle, LH, FSH and combination LH/FSH using quantitative real-time PCR (qPCR. The qPCR results analysis showed that administration of gonadotropins affected a significant change in expression of some RA signaling related genes in the monkey testis. The gonadotropins, either alone or in combination dramatically increased expression of CRABP2 (p≤0.001, whereas there was a decrease in ALDH1A2 expression (p≤0.001. Moreover, combined gonadotropin treatment led to the significant decrease in CRABP1 expression (p≤0.05. These findings are the first evidence that the activity of retinoic acid signaling in the monkey testis is regulated through gonadotropins (LH/FSH levels.

Avian LH and FSH: comparison of several radioimmunoassays

International Nuclear Information System (INIS)

Goldsmith, A.R.; Follett, B.K.

1983-01-01

Comparisons were made between various LH and FSH radioimmunoassays currently being used to measure avian hormones. The two LH assays were the homologous chicken system of Follett et al. (1972) and the turkey assay of Burke et al. (1979). These assays were also used in heterologous arrangement by interchanging the iodinated LH fractions and antisera. Five FSH assays were analyzed: two homologous chicken systems (Scanes et al., 1977; Sakai and Ishii, 1980) an assay based on mammalian materials (rat FSH and anti-ovine FSH antiserum, and one using labelled turkey FSH (Burke et al., 1979) with an anti-chicken FSH antiserum. The potencies of purified chicken and turkey gonadotrophin preparations and of a range of plasma samples from Japanese quail were measured in each assay. The two LH systems showed some degree of species specificity, such that chicken LH was more active than turkey LH in the chicken assay, whereas the reverse was true in the turkey LH assay. The potency estimates of the purified hormones in the various FSH assays were very consistent. The qualitative changes in plasma hormone levels were similar in all assays, although there were some differences in the magnitude of the responses

Occurrence of postmenopausal-like acidic follicle-stimulating hormone (FSH) isoforms precedes the rise of FSH before menopause.

NARCIS (Netherlands)

Thomas, C.M.G.; Span, P.N.; Smeenk, J.M.J.; Hanssen, R.G.; Braat, D.D.M.; Sweep, F.C.

2009-01-01

OBJECTIVE: To assess the glycoform distribution patterns of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during the menstrual cycle at different ages and FSH levels, after menopause, and with premature ovarian failure (POF). DESIGN: Controlled clinical study. SETTING: Healthy

Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter

Directory of Open Access Journals (Sweden)

Surleen Kaur

2016-03-01

Full Text Available Insulin receptor substrate-2 (IRS-2 plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS, insulin resistance and cancer. To predict the transcription factors (TFs responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]. The ibid data is part of author׳s publication (Anjali et al., 2015 [2] that explains Follicle stimulating hormone (FSH mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer. Keywords: IRS-2, TFBS, FSH, SP1, ChIP

A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.

Science.gov (United States)

Abd-Elaziz, Khalid; Duijkers, Ingrid; Stöckl, Lars; Dietrich, Bruno; Klipping, Christine; Eckert, Kelvin; Goletz, Steffen

2017-08-01

What are the differences and similarities of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the novel recombinant human FSH follitropin epsilon expressed in the human cell line GlycoExpress compared with a Chinese hamster ovary (CHO) derived compound and a urinary derived product? Overall follitropin epsilon, with a fully human glycosylation, shows a comparable PK profile at single-dose as well as multiple-dose administration compared to recombinant CHO-derived FSH as well as urinary derived FSH, whereas the PD properties differ from product to product with follitropin epsilon being most active in PD parameters. Recombinant FSH produced in CHO and FSH obtained from the urine of postmenopausal women show comparable PK and PD properties. However, more recently a comparative study of a recombinant FSH produced in the human cell line PerC6 and a CHO-derived FSH preparation revealed differences in PK and PD properties of the molecule. Both studies were randomized, placebo- and comparator-controlled, single-blind phase I studies in healthy pituitary-suppressed female volunteers aged 18 and 40 years. The single-dose, dose escalation study included 19 women (April 2011 to September 2011) with three ascending dose levels per subject or placebo/comparators with a 14-day washout phase between dosings. The multiple-dose study included 57 women (October 2011 to April 2012) in five cohorts with three dose levels versus placebo and two comparators. Randomization to the respective treatment was performed after successful downregulation of the pituitary gland prior to Investigational Medicinal Product dosing. In the single-dose study, 12 subjects received follitropin epsilon (25, 75, 150 and 300 IU) in three of four possible ascending doses and seven subjects received one dose of two comparators (150 IU Bravelle and 150 IU Gonal-f) and placebo in random order in each treatment period. In the multiple-dose study, 30 subjects received follitropin epsilon (75 IU or

The relationship of EDLS, FSH and LH with PIH

International Nuclear Information System (INIS)

Zhang Xuefeng

2003-01-01

To evaluate the role of serum EDLS, FSH and LH in the pathogenesis of PIH, levels of serum EDLS, FSH and LH were measured by radioimmunoassay in 200 patients with PIH. Results: In PIH group, mean level of serum EDLS was significantly higher than that in the normal control group (P<0.01); mean levels of serum FSH and LH were significantly lower than that in the normal control group (P<0.001). EDLS, FSH and LH may play important action in the pathogenesis of PIH

Central hypogonadism due to a giant, "silent" FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG).

Science.gov (United States)

Santi, Daniele; Spaggiari, Giorgia; Casarini, Livio; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Granata, Antonio R M; Carani, Cesare; Simoni, Manuela

2017-06-01

We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male.

Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH in ovulation induction: a prospective, randomized study with cost-minimization analysis

Directory of Open Access Journals (Sweden)

Grassi Giuseppina

2006-07-01

Full Text Available Abstract Background Both recombinant FSH (r-FSH and highly-purified, urinary FSH (HP-uFSH are frequently used in ovulation induction associated with timed sexual intercourse. Their effectiveness is reported to be similar, and therefore the costs of treatment represent a major issue to be considered. Although several studies about costs in IVF have been published, data obtained in low-technology infertility treatments are still scarce. Methods Two hundred and sixty infertile women (184 with unexplained infertility, 76 with CC-resistant polycystic ovary syndrome at their first treatment cycle were randomized and included in the study. Ovulation induction was accomplished by daily administration of rFSH or HP-uFSH according to a low-dose, step-up regimen aimed to obtain a monofollicular ovulation. A bi- or tri-follicular ovulation was anyway accepted, whereas hCG was withdrawn and the cycle cancelled when more than three follicles greater than or equal to 18 mm diameter were seen at ultrasound. The primary outcome measure was the cost of therapy per delivered baby, estimated according to a cost-minimization analysis. Secondary outcomes were the following: monofollicular ovulation rate, total FSH dose, cycle cancellation rate, length of the follicular phase, number of developing follicles (>12 mm diameter, endometrial thickness at hCG, incidence of twinning and ovarian hyperstimulation syndrome, delivery rate. Results The overall FSH dose needed to achieve ovulation was significantly lower with r-FSH, whereas all the other studied variables did not significantly differ with either treatments. However, a trend toward a higher delivery rate with r-FSH was observed in the whole group and also when results were considered subgrouping patients according to the indication to treatment. Conclusion Considering the significantly lower number of vials/patient and the slight (although non-significant increase in the delivery rate with r-FSH, the cost

Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH) in ovulation induction: a prospective, randomized study with cost-minimization analysis.

Science.gov (United States)

Revelli, Alberto; Poso, Francesca; Gennarelli, Gianluca; Moffa, Federica; Grassi, Giuseppina; Massobrio, Marco

2006-07-18

Both recombinant FSH (r-FSH) and highly-purified, urinary FSH (HP-uFSH) are frequently used in ovulation induction associated with timed sexual intercourse. Their effectiveness is reported to be similar, and therefore the costs of treatment represent a major issue to be considered. Although several studies about costs in IVF have been published, data obtained in low-technology infertility treatments are still scarce. Two hundred and sixty infertile women (184 with unexplained infertility, 76 with CC-resistant polycystic ovary syndrome) at their first treatment cycle were randomized and included in the study. Ovulation induction was accomplished by daily administration of rFSH or HP-uFSH according to a low-dose, step-up regimen aimed to obtain a monofollicular ovulation. A bi- or tri-follicular ovulation was anyway accepted, whereas hCG was withdrawn and the cycle cancelled when more than three follicles greater than or equal to 18 mm diameter were seen at ultrasound. The primary outcome measure was the cost of therapy per delivered baby, estimated according to a cost-minimization analysis. Secondary outcomes were the following: monofollicular ovulation rate, total FSH dose, cycle cancellation rate, length of the follicular phase, number of developing follicles (>12 mm diameter), endometrial thickness at hCG, incidence of twinning and ovarian hyperstimulation syndrome, delivery rate. The overall FSH dose needed to achieve ovulation was significantly lower with r-FSH, whereas all the other studied variables did not significantly differ with either treatments. However, a trend toward a higher delivery rate with r-FSH was observed in the whole group and also when results were considered subgrouping patients according to the indication to treatment. Considering the significantly lower number of vials/patient and the slight (although non-significant) increase in the delivery rate with r-FSH, the cost-minimization analysis showed a 9.4% reduction in the overall therapy

The -29G/A FSH receptor gene polymorphism is associated with higher FSH and LH levels in normozoospermic men.

Science.gov (United States)

Tamburino, L; La Vignera, S; Tomaselli, V; Condorelli, R A; Cannarella, R; Mongioì, L M; Calogero, A E

2017-10-01

The functional role of the FSHR promoter -29G/A polymorphism (rs1394205) in men is not clear. Some studies failed to find a relationship between the FSHR -29G/A and follicle-stimulating hormone (FSH) levels and did not associate the SNP with male infertility. Only one study showed that the FSHR -29 SNP modulates serum FSH levels in Baltic young male cohort. Because the SNP -29G/A has to be shown to have a strong effect on in vitro transcription activity of the FSHR promoter and the activation of FSHR is necessary for a normal FSH function, this study was undertaken to assess whether the FSHR -29G/A SNP modulates the gonadal endocrine function in men. A total of 200 men with alteration of conventional sperm parameters or normozoospermia (according to the parameters WHO 2010), were genotyped by TaqMan Assay. Hormone levels were measured by immunoassay, and sperm analysis was performed according to the World Health Organization criteria. A significant gradient of increasing FSH levels across the FSHR -29G/A genotypes was observed (p men (n = 110), those with FSHR -29A-allele carriers (GA + AA and AA) had higher serum FSH (p men with the GG genotype. The carrier status of rs1394205 genotypes did not affect the other endocrine parameters neither in men with altered sperm parameters nor in normozoospermic men. The FSHR -29G/A polymorphism modulates FSH and, for the first time, LH serum levels and BMI in normozoospermic men. These findings underline the importance to pay close attention to the studies of genetic variations associated with clinical-endocrine parameters.

Regulation and regulatory role of WNT signaling in potentiating FSH action during bovine dominant follicle selection.

Directory of Open Access Journals (Sweden)

P S P Gupta

Full Text Available Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest and F2 (second largest follicles isolated at predeviation (PD and onset of diameter deviation (OD stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM, PD, OD and early dominance (ED stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

Modulation of gene expression in small follicle porcine granulosa cells by human follicle stimulating hormone (hFSH)

Energy Technology Data Exchange (ETDEWEB)

Calvo, F.O.; Ryan, R.J.; Woloschak, G.E.

1986-03-01

Small follicle (1-3 mm) porcine granulosa cells (SFPGF) were isolated by puncture, aspiration and cultured under standard conditions in DMEM, HEPES, BSA, MIX. At the start of culture, cells were stimulated with 100ng hFSH/ml. At various times afterwards total cellular RNA was prepared using guanidine-hydrochloride solubilization, phenol extraction and precipitation from 3M NaOAc, pH 6.0. RNA was 5'-end labelled with /sup 32/P in a kinase reaction and hybridized to an excess of clone-specific DNA immobilized on nitrocellulose filters using stringent hybridization and wash conditions. After autoradiography the RNA hybridized to the DNA blot filter were quantitated by microdensitometry. Hybridization to parent plasmid was negative. RNA derived from control cultures showed patterns of hybridization similar to those obtained from freshly obtained cells. Results of these experiments demonstrate hFSh induction of RNA specific for transferrin receptor, ..cap alpha..-interferon, H-ras, and K-ras. Increased RNA levels were apparent within 10 min of treatment and had declined by 180 min. Expression of actin, p53 and for RNAs declined by 10 min of hFSH addition but was enhanced by 160 min. Levels of ..beta..-interferon, myc, mos, abl and yb RNAs were not detectable under these conditions. These results demonstrate specific gene modulation in SFPGC cultured with hFSH.

Effects of estradiol and FSH on maturation of the testis in the hypogonadal (hpg mouse

Directory of Open Access Journals (Sweden)

Mayhew Terry M

2008-01-01

Full Text Available Abstract Background The hypogonadal (hpg mouse is widely used as an animal model with which to investigate the endocrine regulation of spermatogenesis. Chronic treatment of these GnRH-deficient mice with estradiol is known to induce testicular maturation and restore qualitatively normal spermatogenesis. The aim of the current studies was to investigate whether these effects of estradiol are direct effects in the testis, or indirect actions via paradoxical stimulation of FSH secretion from the pituitary gland. Methods Initially, Western blot and immunohistochemistry were used to analyse tissues from hpg mice to identify potential sites of action of estradiol. In the main study, hpg mice were treated for 50 days with either an estradiol implant or daily injections of recombinant human FSH, or a combination of both, to determine whether estradiol would have an additive or synergistic effect with FSH on testis development, as assessed by histological analysis and stereological quantification of Leydig, Sertoli and germ cell proliferation. Results Western blot analysis revealed ERα immunoreactive bands of appropriate molecular weight in extracts of testis and pituitary glands from hpg mice, and immunohistochemical studies confirmed ERα in nuclei of anterior pituitary cells and Leydig and peritubular cells in hpg mice. Histological and morphometric analyses revealed that estradiol treatment alone was as effective as FSH in promoting Sertoli cell production and proliferation of the seminiferous epithelium, resulting in the production of elongating spermatids. Combined estradiol and FSH treatment did not produce a greater effect than either treatment alone, though an increased dose of FSH significantly increased seminiferous tubule volume and testis weight and increase Sertoli cell numbers further within the same time frame. In contrast, estradiol caused substantial increases in the wet weight of the seminal vesicles, whereas FSH was without effect on

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH), ch. 10

International Nuclear Information System (INIS)

Franchimont, P.

1976-01-01

A radioimmunoassay for FSH and LH is described. Both FSH and LH were labelled with 131 I by the Greenwood method. The FSH iodination mixture is purified by passing over a column of DEAE cellulose. The LH iodination mixture can be purified by sephadex gel filtration or by cellulose adsorption chromatography. After incubation, the bound and free-labelled hormones are separated by the double antibody technique

Measurement of rat serum FSH by radioreceptor assay and comparison with radioimmunoassay

International Nuclear Information System (INIS)

Minegishi, Takashi; Igarashi, Masao; Wakabayashi, Katsumi

1980-01-01

Follicle stimulating hormone (FSH) in rat serum is successfully measured by a radioreceptor assay system employing PMS-treated immature rat ovary. The non-specific inhibitory effect of serum was partially overcome by the addition of merthiolate to every component, while the residual effect was compensated for by using FSH-free serum which was prepared by passing the pooled female diestrous rat sera through an immunoadsorbent column packed with anti-ovine FSH-coupled Sepharose 4B. The assay system consisted of 100 μl of Tris-MgCl 2 -BSA or standard, 100 μl of FSH-free serum or sample, 100 μl of the receptor preparation and 100 μl of 125 I-FSH. The incubation was carried out for 4 hr at 37 0 C and 500 μl of cold Tris-MgCl 2 -BSA was used for the termination. Serum FSH could be measured within a range of 0.125 - 16 ng NIAMDD rat FSH I-3/tube. The mean within-assay coefficient of variation was 10.5%. The mean between-assay coefficient of variation was 11.0%. The assay values obtained by RRA showed a good correlation to those by RIA under the same physiological states of the animals. The ratio of the assay values, RRA/RIA, was found to change according to the sex and the physiological states, e.g. around 1.3 in normal males and 1.7 in orchiectomized animals and 2.21 in female rats. Serum FSH levels in female rats obtained by RRA and RIA changed almost in parallel until 20:00 (hr) of proestrous day, but after the first surge of serum FSH they were not parallel. These facts seem to indicate possible changes in the affinity of FSH with its receptor according to the state of animals and lead to the problem of the heterogeneity of FSH. (author)

Diagnostic evaluation of serum FSH and LH in primary amenorrhea by radioimmunoassay

International Nuclear Information System (INIS)

Hong, I.S.; Kim, G.E.; Yoo, H.S.; Lee, J.T.; Park, C.Y.

1980-01-01

The usefulness of single, random measurements of serum FSH and LH in the diagnosis of primary amenorrhea by radioimmunoassay was investigated. The 16 patients were divided into 3 groups by the level of serum FSH and LH. The first group with increased level of serum FSH and LH is five patients, all of these are related to the acquired or congenital abnormality of the ovary. Further studies indicated include buccal smear, chromosome analysis, gynecography and laparoscopy. The second group with normal serum FSH and LH is nine patients, four patients of these are related to the developmental anomaly of the Mullerian duct and five patients are undetermined origin. Further studies indicated include laparoscopy and gynecography. The third group with decreased serum FSH and normal or decreased serum LH is two patients, one of these is related to the pituitary function, isolated FSH deficiency, the other is undetermined origin. Further studies indicated include the pituitary function test, LH-RH stimulation test, skull radiography. Determination of serum FSH and LH levels does not permit a specific etiologic diagnosis of promary amenorrhea. However the serum levels of FSH and LH can be used to differentiate the principal area of the investigation and can be of assistance in choosing more specific testing procedures. (Author)

Inter-laboratory validation of the measurement of follicle stimulating hormone (FSH after various lengths of frozen storage

Directory of Open Access Journals (Sweden)

Behr Barry

2010-11-01

Full Text Available Abstract Background Serum follicle stimulating hormone (FSH levels are used clinically to evaluate infertility, pituitary and gonadal disorders. With increased frequency of research collaborations across institutions, it is essential that inter-laboratory validation is addressed. Methods An inter-laboratory validation of three commercial FSH immunoassays was performed with human serum samples of varying frozen storage length (2 batches of 15 samples each at -25 degree C. Percentage differences and Bland-Altman limits of agreement were calculated. Results The inter- and intra-laboratory consistency of FSH values with the same assay manufacturer was much higher after shorter-term storage (frozen for less than 11 months, mean percentage degradation less than 4% than after long-term storage (2-3 years, mean percentage degradation = 23%. Comparing assay results from different manufacturers, there was similar overall long term degradation as seen with the same manufacturer (-25%, however the degradation was greater when the original FSH was greater than 20 mIU/mL relative to less than 10 mIU/mL (p Conclusion The findings suggest that degradation of serum samples stored between 11 months and 2-3 years at -25 degrees C can lead to unstable FSH measurements. Inter-laboratory variability due to frozen storage time and manufacturer differences in assay results should be accounted for when designing and implementing research or clinical quality control activities involving serum FSH at multiple study sites.

Effect of the FSH receptor single nucleotide polymorphisms (FSHR 307/680) on the follicular fluid hormone profile and the granulosa cell gene expression in human small antral follicles

DEFF Research Database (Denmark)

Borgbo, Tanni Kjær; Jeppesen, J V; Lindgren, I

2014-01-01

), by evaluating the hormone and gene expression profiles of human small antral follicles collected under physiological conditions in connection with fertility preservation. In total 69 women at various time during the menstrual cycle were included in this study. The intrafollicular hormone content of 179...... was significantly increased, whereas AMH gene expression was significantly reduced for the G/G genotype. In follicles >6 mm, estradiol and CYP19A1 gene expression levels were significantly higher for the G/G genotype. In conclusion, significant changes were observed between the FSHR 307/680 polymorphisms in human......The most pronounced effects of FSH signalling are potentially displayed in the follicle fluid, which acts as a reservoir for FSH-induced granulosa cell (GC) secreted hormones. This study investigates the effects of two common polymorphisms of FSHR, FSHR 307 (rs6165) and FSHR 680 (rs6166...

Costs and outcomes associated with IVF using recombinant FSH.

Science.gov (United States)

Ledger, W; Wiebinga, C; Anderson, P; Irwin, D; Holman, A; Lloyd, A

2009-09-01

Cost and outcome estimates based on clinical trial data may not reflect usual clinical practice, yet they are often used to inform service provision and budget decisions. To expand understanding of assisted reproduction treatment in clinical practice, an economic evaluation of IVF/intracytoplasmic sperm injection (ICSI) data from a single assisted conception unit (ACU) in England was performed. A total of 1418 IVF/ICSI cycles undertaken there between October 2001 and January 2006 in 1001 women were analysed. The overall live birth rate was 22% (95% CI: 19.7-24.2), with the 30- to 34-year age group achieving the highest rate (28%). The average recombinant FSH (rFSH) dose/cycle prescribed was 1855 IU. Average cost of rFSH/cycle was 646 pound(SD: 219 pound), and average total cost/cycle was 2932 pound (SD: 422 pound). Economic data based on clinical trials informing current UK guidance assumes higher doses of rFSH dose/cycle (1750-2625 IU), higher average cost of drugs/cycle (1179 pound), and higher average total cost/cycle (3266 pound). While the outcomes in this study matched UK averages, total cost/cycle was lower than those cited in UK guidelines. Utilizing the protocols and (lower) rFSH dosages reported in this study may enable other ACU to provide a greater number of IVF/ICSI cycles to patients within given budgets.

Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period.

Science.gov (United States)

Grisendi, Valentina; Spada, Elena; Argento, Cindy; Plebani, Maddalena; Milani, Silvano; Seracchioli, Renato; Volpe, Annibale; La Marca, Antonio

2014-06-01

High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11 IU for every year of age (1 IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve.

Correlation between FSH, LH and prolactin serum levels. [Radioimmunoassay of hormones

Energy Technology Data Exchange (ETDEWEB)

Krause, W [Giessen Univ. (Germany, F.R.)

1978-01-01

In 188 males FSH, LH, and prolactin serum levels determined by radioimmunoassay from a single blood sample were found to be closely correlated. No correlation appeared to testosterone levels. The same correlation is observed, if serum levels of FSH, LH, and prolactin are measured after stimulation with LH-RH and TRH. In order to explain the close correlation, in five young men hormone levels were measured at 2-min-intervals over a period of 2 hours. Peaks of prolactin often correspond to those of FSH and LH, and a statistical correlation was found in two cases between FSH and prolactin. Results suggest a common releasing mechanism, which is superposed to the main mediating mechanism.

Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation.

Science.gov (United States)

Chowdhury, Indrajit; Thomas, Kelwyn; Zeleznik, Anthony; Thompson, Winston E

2016-05-01

Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E2) and progesterone (P4). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E2 and P4 synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs. © 2016 The authors.

An economic evaluation of highly purified HMG and recombinant FSH based on a large randomized trial.

Science.gov (United States)

Wechowski, Jaroslaw; Connolly, Mark; McEwan, Philip; Kennedy, Richard

2007-11-01

Public funding for IVF is increasingly being challenged by health authorities in an attempt to minimize health service costs. In light of treatment rationing, the need to consider costs in relation to outcomes is paramount. To assess the cost implications of gonadotrophin treatment options, an economic evaluation comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) has been conducted. The analysis is based on individual patient data from a large randomized controlled trial (n = 731) in a long agonist IVF protocol. The economic evaluation uses a discrete event simulation model to assess treatment costs in relation to live births for both treatments based on published UK costs. After one cycle the mean costs per IVF treatment for HP-HMG and rFSH were pound2396 (95% CI pound2383-2414) and pound2633 ( pound2615-2652), respectively. The average cost-saving of pound237 per IVF cycle using HP-HMG allows one additional cycle to be delivered for every 10 cycles. With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound8893 compared with pound11,741 for rFSH (P cost-saving potential of HP-HMG in IVF was still apparent after varying critical cost parameters in the probabilistic sensitivity analysis.

Dose of recombinant FSH and oestradiol concentration on day of HCG affect embryo development kinetics

DEFF Research Database (Denmark)

Muñoz, Manuel; Cruz, María; Humaidan, Peter

2012-01-01

During follicular growth, the follicle is exposed to an almost ever-changing composition of isoforms of FSH and LH, which causes a number of different and divergent biological effects. Through a time-lapse system, embryo kinetics were examined following the use of FSH only (recombinant FSH, rFSH)...

HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation.

Science.gov (United States)

Wex-Wechowski, Jaro; Abou-Setta, Ahmed M; Kildegaard Nielsen, Sandy; Kennedy, Richard

2010-08-01

The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3-58.1%) for HP-HMG and 44.6% (40.2-49.0%) for rFSH (OR 1.44, 95% CI 1.12-1.85; Pcosts per IVF treatment for HP-HMG and rFSH were pound5393 ( pound5341-5449) and pound6269 ( pound6210-6324), respectively (number needed to treat to fund one additional treatment was seven; Pcosts applied, the median cost per IVF baby delivered with HP-HMG was pound11,157 ( pound11,089-11,129) and pound14,227 ( pound14,183-14,222) with rFSH (Pcost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Isolated low follicle stimulating hormone (FSH in infertile males – a preliminary report

Directory of Open Access Journals (Sweden)

Nader Salama

2013-09-01

Full Text Available Objectives: High levels of follicle stimulating hormone (FSH in infertile males received a significant attention and exploration. Studies investigating the isolated deficiency of FSH in males are few, and its real prevalence is still unknown. Therefore, the objectives of the current study was to report the prevalence of isolated low FSH in infertile males and highlight their demographics and standard sperm parameters. Methods: Records of 3335 infertile men were retrospectively checked. Patients with isolated low FSH were retrieved. FSH levels were categorized into 3 groups based on the number of affected sperm parameter (s. Study variables were also arranged into 2 groups in relation to smoking history. A control group was included to document the changes in sperm morphology. Results: Isolated low FSH (1.146 ± 0.219 mIU/mL was found in 29 (0.87% patients. All patients showed at least one abnormal sperm parameter. The abnormal parameters were present in different combinations within the same patient but with no significant correlations with the FSH levels. The FSH levels got lower as the number of the affected sperm parameters increased although the decline was insignificant. The most frequent abnormal parameter presented was sperm morphology (86.2%. Anomalous sperm morphology was highly and significantly demonstrated in the head; specifically in acrosome. Abnormal sperm parameters were present in both smoking and nonsmoking groups but with no significant differences in between. Conclusions: Isolated low FSH among infertile males has a low prevalence. This may be associated with abnormality in semen parameters; particularly sperm morphology. These patients are suggested to be found as a primary entity. However, an additional work-up is highly recommended to validate this hypothesis.

Direct actions of androgen, estrogen and anti-Müllerian hormone on primate secondary follicle development in the absence of FSH in vitro.

Science.gov (United States)

Baba, T; Ting, A Y; Tkachenko, O; Xu, J; Stouffer, R L

2017-12-01

remained similar in all groups. However, media concentrations of P4 and E2 at week 5 were lower (P DHT and AMH groups, compared to CTRL (P4 = 93 ± 10 ng/ml; E2 = 4 ± 1 ng/ml). In the second experiment, FSH depletion diminished follicle survival rate (66 ± 8% in control versus 45 ± 9% in no FSH, P = 0.034). E2 plus DHT (31.5 ± 11%) or DHT alone (69 ± 9%) restored follicle survival rate to the control (FSH) level as expected. Also, E2 plus DHT or DHT alone improved antrum formation rate. However, in the absence of FSH, E2 plus DHT or DHT alone did not support growth, in terms of follicle diameter, or steroid (P4 or E2) production after the antral stage. This study is limited to in vitro effects of E2, DHT and AMH during the interval from the secondary to small antral stage of macaque follicular development. In addition, the primate follicle pool is heterogeneous and differs between animals; therefore, even though only secondary follicles were selected, follicle growth and developmental outcomes might differ from one animal to another. This study provides novel information on the possible actions of estrogen and androgen during early follicular development in primates. Our results suggest that sequential exposure of preantral follicles to local factors, e.g. E2 and DHT, followed by gonadotropin once the follicle reaches the antral stage, may better mimic primate folliculogenesis in vivo. Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Center for Translational Research on Reproduction and Infertility 5P50HD071836, and the NIH Primate Centers Program 8P510D011092. There are no conflicts of interest. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Patient preference for a long-acting recombinant FSH product in ovarian hyperstimulation in IVF: a discrete choice experiment.

Science.gov (United States)

van den Wijngaard, L; Rodijk, I C M; van der Veen, F; Gooskens-van Erven, M H W; Koks, C A M; Verhoeve, H R; Mol, B W J; van Wely, M; Mochtar, M H

2015-02-01

choose differently when they have previous experience with long-acting rFSH, or when they have to pay for the medication, hospital visits and treatments themselves. The results of this DCE helps us to understand the trade-off women make in their preference for a long-acting rFSH product or a daily-administrated rFSH product in IVF and may support doctors when counselling patients. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

EFFECT OF FSH β-SUB UNIT AND FSHR GENES POLYMORPHISMS ON SUPEROVULATORY RESPONSE TRAITS

Directory of Open Access Journals (Sweden)

E. Andreas

2015-09-01

Full Text Available Follicle stimulating hormone (FSH is a pituitary expressed glycoprotein hormone that regulatesreproduction in mammals which composed of α and β-sub unit. The β-sub unit dictates its bindingspecificity with their receptor (FSHR. This study aimed to identify polymorphism of FSH β-sub unitand FSHR genes, and its effect to superovulatory response traits on superovulated cows. Study was doneon 32 cows including Angus, Friesian Holstein (FH, Limousin, Simmental and Brahman in CipelangLivestock Embryo Center. Cows used have been treated superovulation and mated by artificialinsemination. Superovulation response (SR, ovulation rate (OR, fertilization percentage (FP andviable transfer embryo percentage (VP were analyzed to investigate the effect of FSH β-sub unit andFSHR polymorphism. Allele frequency of FSH β-sub unit|PstI and FSH|AluI were opposite withinspecies. Mostly B allele and C allele for FSH β-sub unit and FSHR respectively have a high number inBos taurus species while those were in contrast in Bos indicus species. The highest heterozygosity wasfound in FH cattle (0.250 for FSH β-sub unit and Brahman (0.333 for FSHR. Significant effect was found between FSHR gene polymorphism with ovulation rate where CC genotype was higher (P<0.05than CG and GG genotypes.

Average concentrations of FSH and LH in seminal plasma as determined by radioimmunoassay

International Nuclear Information System (INIS)

Milbradt, R.; Linzbach, P.; Feller, H.

1979-01-01

In 322 males, 25 to 50 years of age, levels of LH and FSH respectively were determined in seminal plasma by radioimmunoassay. Average values of 0,78 ng/ml and 3,95 ng/ml were found as for FSH and LH respectively. Sperm count and motility were not related to FSH levels, but were to LH levels. A high count of spermatozoa corresponded to high concentration of LH, and normal motility was associated with higher levels of LH as compared to levels associated with asthenozoospermia. With respect to count of spermatozoa of a single or the average patient, it is suggested that the ratio of FSH/LH would be more meaningful than LH level alone. (orig.) [de

Cellular regulation of basal and FSH-stimulated cyclic AMP production in irradiated rat testes

International Nuclear Information System (INIS)

Kangasniemi, M.; Kaipia, A.; Toppari, J.; Mali, P.; Huhtaniemi, I.; Parvinen, M.

1990-01-01

Basal and follicle-stimulating hormone (FSH)-stimulated cyclic AMP (cAMP) productions by seminiferous tubular segments from irradiated adult rats were investigated at defined stages of the epithelial cycle when specific spermatogenic cells were low in number. Seven days post-irradiation, depletion of spermatogonia did not influence the basal cAMP production, but FSH response increased in stages II-VIII. Seventeen days post-irradiation when spermatocytes were low in number, there was a small increase in basal cAMP level in stages VII-VIII and FSH-stimulated cAMP production increased in stages VII-XII and XIII-I. At 38 days when pachytene spermatocytes and round spermatids (steps 1-6) were low in number, a decreased basal cAMP production was measured in stages II-VI and IX-XII. FSH-stimulated cAMP output increased in stages VII-XII but decreased in stages II-VI. At 52 days when all spermatids were low in number, basal cAMP levels decreased in all stages of the cycle, whereas FSH response was elevated only in stages VII-XII. All spermatogenic cell types seem to have an effect on cAMP production by the seminiferous tubule in a stage-specific fashion. Germ cells appear to regulate Sertoli cell FSH response in a paracrine way, and a part of cAMP may originate from spermatids stimulated by an unknown FSH-dependent Sertoli cell factor. The FSH-dependent functions may control such phenomena as spermatogonial proliferation, final maturation of spermatids, and onset of meiosis

Individualization of the FSH starting dose in IVF/ICSI cycles using the antral follicle count

Directory of Open Access Journals (Sweden)

La Marca Antonio

2013-02-01

Full Text Available Abstract Background The FSH starting dose is usually chosen according to women’s age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC, which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles. Methods This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505 were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model. Results A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively. Conclusions The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice.

The Quantity and Quality of Brahman Cross Cattle Embryo After Injected FSH and PMSG

Directory of Open Access Journals (Sweden)

Adriani Adriani

2009-05-01

Full Text Available Twenty cattles were used in this experiment to determine the quantity and quality of embryo after injected FSH (follicle stimulating hormone and PMSG (pregnant mare serum gonadotrophin in Brahman Cross Cattle. The experiment was assigned into Completely Randomized Design with 5 treatments and 4 replications. The treatments were T1 = 4 mg of FSH twice a day intra-ovary decreased doses, T2 = 8 mg of FSH twice a day intra-ovary decreased doses, T3 = 300 IU of PMSG single dose intra-ovary, T4 = 600 IU of PMSG single dose intra-ovary, T5 = 40 mg of FSH twice a day intramuscular decreased doses. Trial cattle were oestrus synchronized using 15 mg of PGF2α that gave twice at 11-daily intervals. One day after giving FSH and PMSG was detected the cattle’s oestrus. Washing uterus was done at day 7 after AI using mixture of PBS, FCS and streptomicyn. Data observed were cow performances, embryo quantity and embryo quality. Results of experiment showed that 19 cattle (95% responded oestrus synchronized treatment and super ovulation, whereas 1 cattle (5% did not respond oestrus synchronized treatment and super ovulation. Generally, cattle showed oestrus at 2 – 3 days after giving PGF2α. Eleven cattle (57,90% showed oestrus at 2 days after giving PGF2α whereas the others (8 cattle, 42,10% showed oestrus 3 days giving PGF2α. The treatment of giving FSH and PMSG could increase (P<0,05 embryo. T5 was highest compared the others ( T1, T2, T3 and T4, while T2 and T4 were higher than T1 and T3. Produced total embryo was 82 with average 4,3 ± 5,67 using FSH and PMSG. 8 embryo (9,76%, 9 embryos (10,90, 20 embryo (24,40%, 16 embryo (19,50% and 29 embryos (35,40% were grade A, B, C, D and E respectively. It is concluded that giving of 40 mg FSH intramusculer produce the best embryo donor whereas and giving of FSH 8 mg intraovari was the best effeciency. (Animal Production 11(2: 96-102 (2009 Key Words : Brahman Cross Cattle, embryo, PGF2α PMSG, FSH

Application of an FSH-RIA-kit in the clinical practice

International Nuclear Information System (INIS)

Delzer, W.; Herzmann, H.

1982-01-01

First clinical experiences with an FSH-RIA-kit developed in the Central Institute for Isotope- and Radiation Research are reported. Simultaneously carried out LH and FSH determination during the menstruation cycle with special regard of the middle of the cycle revealed increased hormone values in the preovulatory phase. The problem of evaluation of hormone values achieved by different kits (standards), was investigated simultaneous determination of the sera using the own and an imported kit. (author)

Cumulus expansion, nuclear maturation and connexin 43, cyclooxygenase-2 and FSH receptor mRNA expression in equine cumulus-oocyte complexes cultured in vitro in the presence of FSH and precursors for hyaluronic acid synthesis

Directory of Open Access Journals (Sweden)

Aiudi Giulio

2004-06-01

Full Text Available Abstract The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and in vitro maturation in the presence of equine FSH (eFSH and precursors for hyaluronic acid synthesis. Equine cumulus-oocyte complexes (COC were cultured in a control defined medium supplemented with eFSH (0 to 5 micrograms/ml, Fetal Calf Serum (FCS, precursors for hyaluronic acid synthesis or glutamine according to the experiments. After in vitro maturation, the cumulus expansion rate was increased with 1 microgram/ml eFSH, and was the highest with 20% FCS. It was not influenced by precursors for hyaluronic acid synthesis or glutamine. The expression of transcripts related to cumulus expansion was analyzed in equine cumulus cells before maturation, and after in vivo and in vitro maturation, by using reverse transcription-polymerase chain reaction (RT-PCR with specific primers. Connexin 43, cyclooxygenase-2 (COX-2 and FSH receptor (FSHr mRNA were detected in equine cumulus cells before and after maturation. Their level did not vary during in vivo or in vitro maturation and was influenced neither by FSH nor by precursors for hyaluronic acid synthesis. Results indicate that previously reported regulation of connexin 43 and COX-2 proteins during equine COC maturation may involve post-transcriptional mechanisms.

FSH: fast spaced seed hashing exploiting adjacent hashes.

Science.gov (United States)

Girotto, Samuele; Comin, Matteo; Pizzi, Cinzia

2018-01-01

Patterns with wildcards in specified positions, namely spaced seeds , are increasingly used instead of k -mers in many bioinformatics applications that require indexing, querying and rapid similarity search, as they can provide better sensitivity. Many of these applications require to compute the hashing of each position in the input sequences with respect to the given spaced seed, or to multiple spaced seeds. While the hashing of k -mers can be rapidly computed by exploiting the large overlap between consecutive k -mers, spaced seeds hashing is usually computed from scratch for each position in the input sequence, thus resulting in slower processing. The method proposed in this paper, fast spaced-seed hashing (FSH), exploits the similarity of the hash values of spaced seeds computed at adjacent positions in the input sequence. In our experiments we compute the hash for each positions of metagenomics reads from several datasets, with respect to different spaced seeds. We also propose a generalized version of the algorithm for the simultaneous computation of multiple spaced seeds hashing. In the experiments, our algorithm can compute the hashing values of spaced seeds with a speedup, with respect to the traditional approach, between 1.6[Formula: see text] to 5.3[Formula: see text], depending on the structure of the spaced seed. Spaced seed hashing is a routine task for several bioinformatics application. FSH allows to perform this task efficiently and raise the question of whether other hashing can be exploited to further improve the speed up. This has the potential of major impact in the field, making spaced seed applications not only accurate, but also faster and more efficient. The software FSH is freely available for academic use at: https://bitbucket.org/samu661/fsh/overview.

Patient preference for a long-acting recombinant FSH product in ovarian hyperstimulation in IVF: a discrete choice experiment

NARCIS (Netherlands)

van den Wijngaard, L.; Rodijk, I. C. M.; van der Veen, F.; Gooskens-van Erven, M. H. W.; Koks, C. A. M.; Verhoeve, H. R.; Mol, B. W. J.; van Wely, M.; Mochtar, M. H.

2015-01-01

What factors or attributes of a long-acting recombinant FSH (rFSH) or daily-administrated rFSH influence women's preferences IVF? Patients' preferences for rFSH products are primary influenced by the attribute 'number of injections', but a low 'number of injections' is exchanged for a high 'number

Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF

Directory of Open Access Journals (Sweden)

Gomaa Hala

2012-08-01

Full Text Available Abstract Background To compare the outcome of IVF cycles in women receiving controlled ovarian stimulation with recFSH or recFSH plus low dose hCG. Methods A retrospective case control study, performed at a private practice affiliated with an academic institute. Patients were infertile women who were treated with IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using either low dose hCG in addition to recFSH [N = 88] or recFSH alone [N = 99]. Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized eggs, and serum levels of estradiol. Secondary outcomes were endometrial thickness, cycle cancellations and pregnancy rates. Results A significant increase in number of mature and fertilized eggs was observed in women over 40 years of age using low dose hCG in addition to recFSH. The estradiol level was significantly higher on the day of hCG administration and the serum level of FSH on cycle day 7 and on the day of hCG administration were lower. Conclusion Addition of low dose hCG to recFSH compared with recFSH alone significantly modified cycle characteristics in patients >/= 40 years and could be of potential benefit for IVF cycles in older infertile women.

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism

Directory of Open Access Journals (Sweden)

Guadalupe Vargas

2017-07-01

Full Text Available A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH.

Effects of leptin on FSH cells in the pituitary gland of Podarcis siculus.

Science.gov (United States)

Ferrandino, Ida; Monaco, Antonio; Grimaldi, Maria Consiglio

2015-03-01

Leptin is the hormone synthesised by adipocytes, which plays an important role in regulating appetite and metabolism. In mammals, this pleiotropic hormone also plays a key role in controlling gonadotropin secretion by stimulatory hypothalamic and pituitary actions. However, little is known about leptin in lower vertebrates and particularly few studies are available on reptiles. In the present work, we analysed the action of recombinant human leptin on FSH cells in the pituitary gland of Podarcis siculus female lizards exposed to four different concentrations of the hormone. FSH cells showed a dose-dependent reaction. The data are indicative of the role played by leptin in modulating the cellular activity of such cells in the pituitary gland of P. siculus, similar to what was already reported in mammals. A functional receptor is evidently able to respond to leptin in this lizard, but further comparative studies are needed to understand the role of this hormone in ectothermic vertebrates. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

FSH to estradiol ratio can be used as screening method for mild cognitive impairment in postmenopausal women.

Science.gov (United States)

Hestiantoro, A; Wiwie, M; Shadrina, A; Ibrahim, N; Purba, J S

2017-12-01

To determine the role of anthropometric measurement, menopausal symptoms and biochemical marker changes as screening methods for mild cognitive impairment (MCI) in postmenopausal women Methods: A cross-sectional study included 282 postmenopausal women in Jakarta, further classified into two groups, with and without MCI. Some related variables such as age, body mass index (BMI), duration of menopause, vasomotor symptoms, hormone levels such as follicle stimulating hormone (FSH), luteinizing hormone, leptin, estradiol, and cognitive status, were assessed and analyzed. The FSH levels significantly correlated with MCI incidence (p = 0.018), along with the ratio of FSH/estradiol levels (p = 0.029) and ratio of FSH/soluble leptin receptor (p = 0.011), while other variables did not. By multivariate analysis, the ratio of FSH/estradiol was known as the most significant factor with a probability of having MCI in menopausal women of 1.15. Using the ROC curve, the threshold of the ratio FSH/estradiol to predict MCI was 1.94, with sensitivity 66.5% and specificity 46.8%. The ratio of FSH to estradiol (>1.94) can be used as a screening method for the occurrence of MCI in postmenopausal women.

Validation of a noninvasive diagnostic tool to verify neuter status in dogs: The urinary FSH to creatinine ratio.

Science.gov (United States)

Albers-Wolthers, C H J; de Gier, J; Oei, C H Y; Schaefers-Okkens, A C; Kooistra, H S

2016-09-15

Determining the presence of functional gonadal tissue in dogs can be challenging, especially in bitches during anestrus or not known to have been ovariectomized, or in male dogs with nonscrotal testes. Furthermore, in male dogs treated with deslorelin, a slow-release GnRH agonist implant for reversible chemical castration, the verification of complete downregulation of the hypothalamic-pituitary-gonadal (HPG) axis can be difficult, especially if pretreatment parameters such as the size of the testes or prostate gland are not available. The aims of this study were to validate an immunoradiometric assay for measurement of FSH in canine urine, to determine if the urinary FSH to creatinine ratio can be used to verify the neuter status in bitches and male dogs, as an alternative to the plasma FSH concentration, and to determine if downregulation of the HPG axis is achieved in male dogs during deslorelin treatment. Recovery of added canine FSH and serial dilutions of urine reported that the immunoradiometric assay measures urinary FSH concentration accurately and with high precision. Plasma FSH concentrations (the mean of two samples, taken 40 minutes apart) and the urinary FSH to creatinine ratio were determined before gonadectomy and 140 days (median, range 121-225 days) and 206 days (median, range 158-294 days) after gonadectomy of 13 bitches and five male dogs, respectively, and in 13 male dogs before and 132 days (median, range 117-174 days) after administration of a deslorelin implant. In both bitches and male dogs, the plasma FSH concentration and the urinary FSH to creatinine ratio were significantly higher after gonadectomy, with no overlapping of their ranges. Receiver operating characteristic analysis of the urinary FSH to creatinine ratio revealed a cut-off value of 2.9 in bitches and 6.5 in males to verify the presence or absence of functional gonadal tissue. In male dogs treated with deslorelin, the plasma FSH concentrations and urinary FSH to

Clinical significance of measurement of serum TNF-α, T, FSH and PRL levels in male infertility

International Nuclear Information System (INIS)

Li Tianquan; Zhou Minglian; He Haoming

2011-01-01

Objective: To explore the significance of changes of serum TNF-α, T, FSH and PRL levels in male patients with infertility. Methods: Serum TNF-α, T, FSH and PRL (with RIA) were measured in 36 male patients with infertility and 35 male controls. Results: Serum T level was significantly lower in the patients than those in controls (P<0.01), while the serum TNF-α, FSH and PRL levels were significantly higher in the patients (P<0.01). Serum TNF-α level was negatively correlated with T level in the patients (r=-0.5184, P<0.01) and positively correlated with FSH, PRL levels (r=0.6184, 0.5925, P<0.01). Conclusion: Serum TNF-α, T, FSH and PRL levels were significantly changed in male with infertility and determination of which might useful for prognosis and treatment clinically. (authors)

Cost-effectiveness analysis on the use of rFSH + rLH for the treatment of anovulation in hypogonadotropic hypogonadal women

Directory of Open Access Journals (Sweden)

Papaleo E

2014-06-01

Full Text Available Enrico Papaleo,1 Carlo Alviggi,2 Giorgio Lorenzo Colombo,3,4 Claudio Pisanelli,5,6 Claudio Ripellino,7 Salvatore Longobardi,8 Pier Luigi Canonico91Centro Scienze della Natalità, Gynecological-Obstetrics Department, San Raffaele Hospital, Vita-Salute San Raffaele, Milan, Italy; 2Department of Neuroscience, Reproductive Sciences and Odontostomatology, University “Federico II” of Naples, Naples, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, Italy; 4SAVE Studi Analisi Valutazioni Economiche, Milan, Italy; 5ACO San Filippo Neri, Rome, Italy; 6Società Italiana Di Farmacia Ospedaliera, Milan, Italy; 7CSD Medical Research Srl, Milan, Italy; 8Medical Department, Merck Serono SpA, Rome, Italy; 9Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy Background: Hypogonadotropic hypogonadal women are characterized by ovarian functionality deficiency, caused by low concentrations of follicle-stimulating hormone (FSH and luteinizing hormone (LH. To recover reproduction functionality, recommended therapies for ovarian induction involve injections of FSH and LH medications. Objective: Since important differences exist between recombinant and urinary gonadotropin therapies in terms of efficacy and cost, the objective of this study was to develop a cost-effectiveness model to compare recombinant FSH (rFSH + recombinant LH (rLH and highly purified human menopausal gonadotropin (HP-HMG. Methods: A Markov model was developed, considering three cycles of therapy; probability of pregnancy and miscarriage were considered, and the efficacy was evaluated in terms of pregnancy occurrence. The perspective of the model was that of the Italian Health Service, so only direct cost (drugs, specialist visits, patient examinations, and hospitalizations were included. Results: rFSH + rLH is associated with a higher total cost (€3,453.50 and higher efficacy (0.87 compared with HP-HMG (€2,719.70 and 0.50. rFSH + r

Development and Application of a Sensitive, Second Antibody Format Enzymeimmunoassay (EIA) for Estimation of Plasma FSH in Mithun (Bos frontalis).

Science.gov (United States)

Mondal, Mohan; Baruah, Kishore Kumar; Prakash, B S

2016-01-01

Mithun (Bos frontalis) is a semi-wild rare ruminant species. A simple sensitive enzymeimmunoassay suitable for assaying FSH in the blood plasma of mithun is not available which thereby limits our ability to understand this species reproductive processes. Therefore, the aim of this article was to develop a simple and sensitive enzymeimmunoassay (EIA) for estimation of FSH in mithun plasma and apply the assay to understand the estrous cycle and superovulatory process in this species. To accomplish this goal, biotinylated FSH was bridged between streptavidin-peroxidase and immobilized antiserum in a competitive assay. Forty microlitre mithun plasma was used directly in the EIA. The FSH standards were prepared in hormone free plasma and ranged from 5-1280 pg/well/40 μL. The sensitivity of EIA was 5 pg/well FSH, which corresponds to 0.125 ng/mL plasma and the 50% relative binding sensitivity was 90 pg/well/40 μL. Although the shape of the standard curve was not influenced by different plasma volumes viz. 40 and 80 μL, a slight drop in the OD450 was observed with the increasing volume of plasma. Parallelism tests conducted between the endogenous mithun FSH and bovine FSH standards showed good homology between them. Plasma FSH estimated using the developed EIA and commercially available FSH EIA kit in the same samples were correlated (r = 0.98) and showed linearity. Both the Intra- and inter-assay CV were below 6%. Recovery of known concentrations of added FSH showed linearity (r = 0.99). The developed EIA was further validated biologically by estimating FSH in cyclic cows for the entire estrous cycle, in mithun heifers administered with GnRH analogues and in mithun cows during superovulatory treatment with FSH. In conclusion, the EIA developed for FSH determination in mithun blood plasma is simple and highly sensitive for estimation of mithun FSH in all physiological conditions.

Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

International Nuclear Information System (INIS)

Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Glisic, Branka; Kaisarevic, Sonja; Kovacevic, Radmila; Andric, Nebojsa

2013-01-01

Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA. Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. • Atrazine

Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

Energy Technology Data Exchange (ETDEWEB)

Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Glisic, Branka; Kaisarevic, Sonja; Kovacevic, Radmila; Andric, Nebojsa, E-mail: nebojsa.andric@dbe.uns.ac.rs

2013-07-01

Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA. Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. • Atrazine

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis

OpenAIRE

van Tilborg, Theodora C.; Oudshoorn, Simone C.; Eijkemans, Marinus J. C.; Mochtar, Monique H.; van Golde, Ron J. T.; Hoek, Annemieke; Kuchenbecker, Walter K. H.; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B.; Laven, Joop S. E.; Mol, Ben Willem J.; Broekmans, Frank J. M.

2017-01-01

STUDY QUESTION: Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? SUMMARY ANSWER: In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose. WHAT IS KNOWN ALREADY: In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to no...

Predicting ongoing pregnancy following ovulation induction with recombinant FSH in women with polycystic ovary syndrome

NARCIS (Netherlands)

van Wely, Madelon; Bayram, Neriman; van der Veen, Fulco; Bossuyt, Patrick M. M.

2005-01-01

BACKGROUND: Ovulation induction with recombinant FSH (rFSH) is common in women with polycystic ovary syndrome (PCOS) not responding to clomiphene citrate treatment, despite the associated risk of multiple pregnancies. We analysed clinical, ultrasonographic and endocrine parameters during initial

Developmental changes in FSH secretion induced by 5-hydroxytryptophan, naloxone and haloperidol in male and female rats.

Science.gov (United States)

Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

1989-06-01

Follicle-stimulating hormone (FSH) secretion is increased in the immature female rat from day 5 to days 17-18 of life, and decreases steadily thereafter until puberty. It has been reported that estradiol negative feedback and inhibin-like peptides are low during this period, while luteinizing hormone (LH) and FSH sensitivity to LH-releasing hormone (LHRH) are maximal. It was therefore of interest to study the effects of some neurotropic drugs on FSH release at 12 days of age, and to compare their effects at 1 and 20 days. Besides, as developmental patterns and regulation of FSH are different in male and female rats, the experiments were carried out using male and female littermates. The drugs chosen were haloperidol, 5-hydroxytryptophan and naloxone. These drugs release LH in the infantile female rat, the effect decreasing or disappearing as the animal matures; no effects of these drugs have been reported on FSH release in infantile rats to the present time. It was found that haloperidol (0.25 mg/kg), naloxone (2 mg/kg) and 5-hydroxytryptophan (50 mg/kg) markedly increased the already high titers of FSH in the 12-day-old female rat. This effect could not be discerned in newborn rats, and had disappeared at 20 days of age. Male littermates failed to respond at any age. When adult male and female rats in diestrus were tested, all drugs at the chosen doses were ineffective in altering FSH release. These data suggest that the infantile female rat represents an interesting physiological model to evaluate the neural regulation of FSH in a situation in which inhibitory signals provided by inhibin and estrogen in later life are diminished.

Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization.

Science.gov (United States)

Pogrmic-Majkic, Kristina; Samardzija, Dragana; Fa, Svetlana; Hrubik, Jelena; Glisic, Branka; Kaisarevic, Sonja; Andric, Nebojsa

2014-11-01

Premature luteinization is a possible cause of infertility in women. It is currently unknown whether environmental chemicals can induce changes associated with premature luteinization. Using rat granulosa cells (GC) in vitro, we demonstrated that exposure to atrazine (ATR), a widely used herbicide, causes GC phenotype that resembles that of human premature luteinization. At the end of the 48-h stimulation with FSH, ATR-exposed GC showed (1) higher levels of progesterone, (2) overexpression of luteal markers (Star and Cyp11a1), and (3) an increase in progesterone:estradiol ratio above 1. Mechanistic experiments were conducted to understand the signaling events engaged by ATR that lead to this phenotype. Western blot analysis revealed prolonged phosphorylation of protein kinase B (AKT) and cAMP response element-binding protein (CREB) in ATR- and FSH-exposed GC. An increased level of ERK1/2-dependent transcriptional factor CCATT/enhancer-binding protein beta (CEBPB) was observed after 4 h of ATR exposure. Inhibitors of PI3K (wortmannin) and MEK (U0126) prevented ATR-induced rise in progesterone level and expression of luteal markers in FSH-stimulated GC. Atrazine intensified AKT and CEBPB signaling and caused Star overexpression in forskolin-stimulated GC but not in epidermal growth factor (EGF)-stimulated GC. In the presence of rolipram, a specific inhibitor of phosphodiesterase 4 (PDE4), ATR was not able to further elevate AKT phosphorylation, CEBPB protein level, and Star mRNA in FSH-stimulated GC, suggesting that ATR inhibits PDE4. Overall, this study showed that ATR acts as a FSH sensitizer leading to enhanced cAMP, AKT, and CEBPB signaling and progesterone biosynthesis, which promotes premature luteinization phenotype in GC. © 2014 by the Society for the Study of Reproduction, Inc.

Identification of differential gene expression in in vitro FSH treated pig granulosa cells using suppression subtractive hybridization

Directory of Open Access Journals (Sweden)

Tosser-Klopp G

2006-07-01

Full Text Available Abstract FSH, which binds to specific receptors on granulosa cells in mammals, plays a key role in folliculogenesis. Its biological activity involves stimulation of intercellular communication and upregulation of steroidogenesis, but the entire spectrum of the genes regulated by FSH has yet to be fully characterized. In order to find new regulated transcripts, however rare, we have used a Suppression Subtractive Hybridization approach (SSH on pig granulosa cells in primary culture treated or not with FSH. Two SSH libraries were generated and 76 clones were sequenced after selection by differential screening. Sixty four different sequences were identified, including 3 novel sequences. Experiments demonstrated the presence of 25 regulated transcripts. A gene ontology analysis of these 25 genes revealed (1 catalytic; (2 transport; (3 signal transducer; (4 binding; (5 anti-oxidant and (6 structural activities. These findings may deepen our understanding of FSH's effects. Particularly, they suggest that FSH is involved in the modulation of peroxidase activity and remodelling of chromatin.

Intrafollicular Endocrine Milieu After Addition of hCG to Recombinant FSH During Controlled Ovarian Stimulation for In Vitro Fertilization

DEFF Research Database (Denmark)

Thuesen, L L; Andersen, A Nyboe; Loft, A

2014-01-01

CONTEXT: The role of human chorionic gonadotropin (hCG) supplementation on the intrafollicular steroid milieu has been studied. OBJECTIVE: The objective of the study was to assess the impact on steroid levels in follicular fluids (FFs) after different doses of hCG supplementation to recombinant FSH...... protocol with recombinant FSH 150 IU/d and randomized from stimulation day 1 to supplementation with hCG: D0, 0 IU/d; D50, 50 IU/d; D100, 100 IU/d; and D150, 150 IU/d. MAIN OUTCOME MEASURE: Intrafollicular hormone concentrations in relation to treatment groups, follicular sizes, and embryo quality were...... measured. RESULTS: In large follicles, hCG supplementation induced a nearly 3-fold increase of estradiol (nanomoles per liter) [D0: 1496; D50: 3138; D100: 4338; D150: 4009 (P

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary.

Science.gov (United States)

Geber, Selmo; Brandão, Augusto H F; Sampaio, Marcos

2012-06-15

Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student's t-test and Pearson's correlation test. We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

FSHR and LHR Expression and Signaling as Well as Maturation and Apoptosis of Cumulus-Oocyte Complexes Following Treatment with FSH Receptor Binding Inhibitor in Sheep

Directory of Open Access Journals (Sweden)

Suocheng Wei

2017-09-01

Full Text Available Background/Aims: Currently, it remains unknown whether FSH receptor binding inhibitor (FRBI influences follicular development and reproduction functions in humans and animals. The present study aimed to investigate FRBI effects on in vitro maturation (IVM and apoptosis of cumulus-oocyte complexes (COCs of sheep, to determine the effect of FRBI on mRNA and protein levels of FSHR and LHR in COCs, and to elucidate the signal pathway of FRBI effects. Methods: COCs were in vitro cultured for 24h in the IVM media supplemented with varying concentrations of FRBI (0, 10, 20, 30 and 40µg/mL and FSH (10IU/mL. The harvested COCs were observed under an inverted microscope and maturation rates of COCs were determined. Real time RT-PCR and Western blotting were utilized to detect mRNA and protein levels of FSHR and LHR. The concentrations of FSH, LH and caspase-3 were determined using especial ELISA kits for sheep, respectively. Results: Maturation rates of COCs decreased gradually as FRBI concentrations increased from 0 to 40µg/mL, reaching a bottom value of 23.76% of the FRBI-4 group. The maximal apoptosis rate was detected in the FRBI-4 group. IP3 contents of FRBI-3 and FRBI-4 groups were reduced as compared to control group (CG and FSH groups (P<0.05. Levels of FSHR protein of FRBI-3 and FRBI-4 groups as well as LHR protein of FRBI-4 group were significantly less than that of CG and FSH group. FSH contents of four FRBI treatment groups were gradually decreased along with the supplementation doses of FRBI. Caspase-3 contents of FRBI groups were reduced with a maximum reduction of the FRBI-2 group. Conclusion: Our results revealed supplement of FRBI into IVM media could dose-dependently decrease the maturation rate and increase apoptosis rate of sheep COCs. A lower dose of FRBI treatment slightly promoted IP3 production, but a higher dose of FRBI reduced IP3 production. FRBI suppressed the mRNA and protein expression levels of FSHR and LHR in sheep COCs

Selective effects of charge on G protein activation by FSH-receptor residues 551-555 and 650-653.

Science.gov (United States)

Grasso, P; Deziel, M R; Reichert, L E

1995-01-01

Two cytosolic regions of the rat testicular FSH receptor (FSHR), residues 533-555 and 645-653, have been identified as G protein-coupling domains. We localized the activity in these domains to their C-terminal sequences, residues 551-555 (KIAKR, net charge +3) and 650-653 (RKSH, net charge +3), and examined the effects of charge on G protein activation by the C-terminal peptides, using synthetic analogs containing additions, through alanine (A) linkages, of arginine (R, +), histidine (H, +) or both. RA-KIAKR (net charge +4) mimicked the effect of FSHR-(551-555) on guanine nucleotide exchange in rat testis membranes, but reduced its ability to inhibit FSH-stimulated estradiol biosynthesis in cultured rat Sertoli cells. Further increasing net charge by the addition of H (HARA-KIAKR, net charge +5) increased guanosine 5'-triphosphate (GTP) binding, but eliminated FSHR-(551-555) effects on FSH-stimulated steroidogenesis. HA-RKSH (net charge +4) significantly inhibited guanine nucleotide exchange in rat testis membranes, but stimulated basal and potentiated FSH-induced estradiol biosynthesis in cultured rat Sertoli cells. Addition of two H residues (HAHA-RKSH, net charge +5) restored GTP binding and further potentiated basal and FSH-stimulated steroidogenesis. These results suggest that positive charges in G protein-coupling domains of the FSHR play a role in modulating G protein activation and postbinding effects of FSH, such as steroidogenesis.

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI : A multicentre trial and cost-effectiveness analysis

NARCIS (Netherlands)

van Tilborg, Theodora C.; Oudshoorn, Simone C.; Eijkemans, Marinus J. C.; Mochtar, Monique H.; van Golde, Ron J. T.; Hoek, Annemieke; Kuchenbecker, Walter K. H.; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B.; Laven, Joop S. E.; Mol, Ben Willem J.; Broekmans, Frank J. M.; Torrance, Helen L.

2017-01-01

STUDY QUESTION: Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? SUMMARY ANSWER: In women initiating IVF/ICSI, AFC-based individualized FSH dosing

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis

NARCIS (Netherlands)

van Tilborg, Theodora C.; Oudshoorn, Simone C.; Eijkemans, Marinus J. C.; Mochtar, Monique H.; van Golde, Ron J. T.; Hoek, Annemieke; Kuchenbecker, Walter K. H.; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B.; Laven, Joop S. E.; Mol, Ben Willem J.; Broekmans, Frank J. M.; Torrance, Helen L.

2017-01-01

STUDY QUESTION: Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? SUMMARY ANSWER: In women initiating IVF/ICSI, AFC-based individualized FSH dosing

HMG versus rFSH for ovulation induction in developing countries: a cost-effectiveness analysis based on the results of a recent meta-analysis.

Science.gov (United States)

Al-Inany, Hesham G; Abou-Setta, Ahmed M; Aboulghar, Mohamed A; Mansour, Ragaa T; Serour, Gamal I

2006-02-01

Both cost and effectiveness should be considered conjointly to aid judgments about drug choice. Therefore, based on the results of a recent published meta-analysis, a Markov model was developed to conduct a cost-effectiveness analysis for estimation of the cost of an ongoing pregnancy in IVF/intracytoplasmic sperm injection (ICSI) cycles. In addition, Monte Carlo micro-simulation was used to examine the potential impact of assumptions and other uncertainties represented in the model. The results of the study reveal that the estimated average cost of an ongoing pregnancy is 13,946 Egyptian pounds (EGP), and 18,721 EGP for a human menopausal gonadotrophin (HMG) and rFSH cycle respectively. On performing a sensitivity analysis on cycle costs, it was demonstrated that the rFSH price should be 0.61 EGP/IU to be as cost-effective as HMG at the price of 0.64 EGP/IU (i.e. around 60% reduction in its current price). The difference in cost between HMG and rFSH in over 100,000 cycles would result in an additional 4565 ongoing pregnancies if HMG was used. Therefore, HMG was clearly more cost-effective than rFSH. The decision to adopt a more expensive, cost-ineffective treatment could result in a lower number of cycles of IVF/ICSI treatment undertaken, especially in the case of most developing countries.

A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles.

Science.gov (United States)

Allegra, Adolfo; Marino, Angelo; Volpes, Aldo; Coffaro, Francesco; Scaglione, Piero; Gullo, Salvatore; La Marca, Antonio

2017-04-01

The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary

Directory of Open Access Journals (Sweden)

Geber Selmo

2012-06-01

Full Text Available Abstract Background Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. Methods A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student’s t-test and Pearson’s correlation test. Results We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. Conclusions This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

Age and methods of fatal self harm (FSH). Is there a link?

Science.gov (United States)

Tadros, G; Salib, E

2000-09-01

To examine the methods of fatal self harm (FSH) used by the elderly compared to young adults. We compared the methods of FSH used by all the elderly over 60 years of age to those used by all younger adults, over 16 and under 60, in the city of Birmingham and Solihull over a period of 4 years, 1995-1998. We applied the term FSH to all deceased who were subjects of Coroner's inquests and attracted verdicts of suicide and open verdicts. A significantly higher proportion of the elderly who fatally harmed themselves did so by drowning and asphyxia compared to the younger age group (p suicide among elderly men and women were hanging and self-poisoning by overdose, respectively. The study shows that the most common method of suicide in the elderly is poisoning by drug overdose. It raises the question about the quantity of drugs prescribed for the elderly, e.g. antidepressants, sedatives and pain killers. The study did not confirm previous reports that violent methods are used more frequently with increasing age. Copyright 2000 John Wiley & Sons, Ltd.

Avaliação da Reserva Ovariana: Comparação entre a Dosagem do FSH Basal e o Teste do Clomifeno Evaluation of Ovarian Reserve: Comparison Between Basal FSH Level and Clomiphene Test

Directory of Open Access Journals (Sweden)

Rodrigo Coelho Franco

2002-06-01

Full Text Available Objetivo: avaliar a reserva ovariana por meio da dosagem do FSH no 3º dia do ciclo menstrual, comparando-o com o teste do clomifeno, e correlacionar os resultados com a resposta ovariana à hiperestimulação controlada com gonadotrofinas para a fertilização in vitro. Métodos: foram selecionadas 49 pacientes com idade superior a 30 anos que apresentavam quadro clínico de infertilidade há pelo menos 1 ano. Foi realizada avaliação da reserva ovariana destas pacientes pelo teste do citrato de clomifeno. Posteriormente, 26 das 49 pacientes foram submetidas à hiperestimulação ovariana controlada com gonadotrofinas. Destas 26 pacientes, 18 tiveram boa resposta à hiperestimulação ovariana e 8, má resposta. Foram calculadas as médias e os desvios-padrão referentes aos valores do FSH do 3º dia, do 10º dia e do somatório de ambos, no grupo das pacientes que responderam favoravelmente à estimulação ovariana. Posteriormente foi realizada a correlação dos valores obtidos com a resposta ovariana após a estimulação dos ovários com gonadotrofinas. Resultados: empregando-se a dosagem do FSH no 10º dia (média somada a 2 desvios-padrão com valor >16,1 UI/mL para predizer a má resposta ovariana ao teste do clomifeno, observaram-se sensibilidade, especificidade e valores preditivos positivo e negativo de 50, 100, 100 e 81,8%, respectivamente. Considerando-se o teste do clomifeno positivo quando o valor do somatório das dosagens do FSH do 3º e do 10º dia somado a dois desvios-padrão foi > 22,6 UI/mL, obtiveram-se sensibilidade de 62,5%, especificidade de 100%, valor preditivo positivo de 100% e valor preditivo negativo de 85,7% . O uso da dosagem única do FSH no 3º dia do ciclo acima de 10 UI/mL para predizer a má resposta ovariana mostrou sensibilidade de 87%, especificidade de 100%, valor preditivo positivo de 100% e valor preditivo negativo de 94,7%. Conclusão: no presente estudo, a dosagem única do FSH no 3º dia do ciclo

Diferentes origens do Hormônio Folículo Estimulante (FSH influenciam a viabilidade e o desenvolvimento de folículos pré-antrais caprinos

Directory of Open Access Journals (Sweden)

Deborah de Melo Magalhães

2009-10-01

Full Text Available The aim of this study was to evaluate the effects of pituitary (pFSH or recombinant (rFSH FSH on the survival and growth of caprine preantral follicles. Caprine ovarian tissues were in vitro cultured for one or seven days in Minimum Essential Medium (MEM alone or containing 10, 50, 100 and 1000 ng/ml of pFSH or rFSH. Control tissues (non-cultured and those cultured were processed for histological and ultrastructural studies. In addition, follicular and oocyte diameter were analysed. After seven days of culture, only 50 ng/ml of rFSH maintained the percentage of normal follicles similar to control. Moreover, 10 ng/ml of pFSH and all the concentrations of rFSH promoted primordial follicles activation. In addition, the presence of 50 ng/ml of rFSH promoted the highest follicular diameter at day seven of culture. In conclusion, 50 ng/ml of rFSH maintained the ultrastructural integrity of caprine preantral follicles, promoted primordial follicles activation and further growth of cultured follicles.

Recovery of ovarian function after postradiation menopause. Do FSH levels have a definitive prognostic value?; Recuperation de fonctionnement ovarien apres menopause radio-induite. L`hormone folliculostimulante (FSH) a-t-elle une valeur pronostique definitive?

Energy Technology Data Exchange (ETDEWEB)

Letur-Konirsch, H. [Hopital Necker-Enfants-Malades, 75 - Paris (France); Guis, F. [Hopital Antoine-Beclere, Clamart (France)

1996-08-01

Menopause, conventionally defined as the permanent cessation as a result of loss of ovarian follicular activity, is biologically expressed by the collapse of plasma levels and increased plasma levels of the gonadotrophins FSH (follicle stimulating hormone) and LH (luteinizing hormone). At present, estimation of the ovarian follicle reserve is based on endocrine capacity tests of the ovaries, with increased FSH representing the first sign of exocrine ovarian failure. We report the case of one of our amenorrhoeic patients after chemotherapy, total body radiation and allogeneic bone marrow transplantation for acute immuno-blastic leukaemia. This patient was included in an in vitro fertilization with oocyte donation (IVF-OD) programme for iatrogenic premature ovarian failure with increased FSH levels. Instead of high levels of gonadotrophins, this young woman recovered spontaneous follicular developments, benefited from standard IVF with her own oocytes and brought a twin pregnancy to term. This observation shows that a high FSH level is not a definitive prediction of ovarian exocrine capacity. In young women of child-bearing age such as these wanting a child and showing signs of endogenous estrogen impregnation, evaluation of the existence and quality of follicular development is an important factor. (author). 13 refs.

Antibody Selection for Cancer Target Validation of FSH-Receptor in Immunohistochemical Settings

Directory of Open Access Journals (Sweden)

Nina Moeker

2017-10-01

Full Text Available Background: The follicle-stimulating hormone (FSH-receptor (FSHR has been reported to be an attractive target for antibody therapy in human cancer. However, divergent immunohistochemical (IHC findings have been reported for FSHR expression in tumor tissues, which could be due to the specificity of the antibodies used. Methods: Three frequently used antibodies (sc-7798, sc-13935, and FSHR323 were validated for their suitability in an immunohistochemical study for FSHR expression in different tissues. As quality control, two potential therapeutic anti-hFSHR Ylanthia® antibodies (Y010913, Y010916 were used. The specificity criteria for selection of antibodies were binding to native hFSHR of different sources, and no binding to non-related proteins. The ability of antibodies to stain the paraffin-embedded Flp-In Chinese hamster ovary (CHO/FSHR cells was tested after application of different epitope retrieval methods. Results: From the five tested anti-hFSHR antibodies, only Y010913, Y010916, and FSHR323 showed specific binding to native, cell-presented hFSHR. Since Ylanthia® antibodies were selected to specifically recognize native FSHR, as required for a potential therapeutic antibody candidate, FSHR323 was the only antibody to detect the receptor in IHC/histochemical settings on transfected cells, and at markedly lower, physiological concentrations (ex., in Sertoli cells of human testes. The pattern of FSH323 staining noticed for ovarian, prostatic, and renal adenocarcinomas indicated that FSHR was expressed mainly in the peripheral tumor blood vessels. Conclusion: Of all published IHC antibodies tested, only antibody FSHR323 proved suitable for target validation of hFSHR in an IHC setting for cancer. Our studies could not confirm the previously reported FSHR overexpression in ovarian and prostate cancer cells. Instead, specific overexpression in peripheral tumor blood vessels could be confirmed after thorough validation of the antibodies used.

PENGARUH PEMBERIAN MONOSODIUM GLUTAMAT (MSG PADA TIKUS JANTAN (Rattus Norvegicus TERHADAP FSH DAN LH

Directory of Open Access Journals (Sweden)

Zulkarnain Edward

2010-09-01

Full Text Available AbstrakKemajuan teknologi informasi membawa dampak terhadap perubahan gaya hidup masyarakat, termasuk perubahan pola konsumsi makanan yang lebih banyak mengkonsumsi jenis makanan cepat saji, makanan kemasan dan makanan awetan yang belakangan ini semakin banyak dijual dipasar tradisional dan swalayan. Penggunaan bahan tambahan makanan sering dijumpai, salah satunya adalah bahan penyedap yang banyak sekali digunakan seperti senyawa L-asam glutamat yang digunakan dalam bentuk garam yaitu monosodium glutamat (MSG. Berbagai merk dagang MSG telah dikenal dimasyarakat secara luas seperti ajinomoto, vetsin, micin, sasa, miwon dan sebagainya.MSG adalah garam monosodium dengan asam glutamat yang sering digunakan sebagai bahan penyedap masakan untuk merangsang selera makan. Pemberian MSG mengakibatkan gangguan hormonal pada hewan coba, ion glutamat dalam sirkulasi portal akan mempengaruhi hipotalamus dalam memproduksi GnRH yang selanjutnya akan mengganggu hipofise anterior dalam memproduksi FSH dan LH. Fungsi FSH adalah untuk bekerja pada tubulus seminiferus terutama pada sel sertoli untuk meningkatkan spermatogenesis, sedangkan LH berfungsi pada sel Leydig untuk mengatur sekresi testosteron.Penelitian ini bersifat eksperimen dengan rancangan post only group design. Penelitian dilakukan di laboratorium Biologi dan laboratorium Biokimia Fakultas Kedokteran Unand Padang dari tanggal 20 Desember 2009 sampai 30 Februari 2010. Populasi adalah tikus putih jantan strain Jepang (Rattus norvegicus yang berasal dari laboratorium Fakultas Matematika dan Ilmu Pengetahuan Alam Unand. Sampel berjumlah 20 ekor dibagi atas 4 kelompok dengan satu kelompok kontrol dan tiga kelompok perlakuan. Dosis MSG yang digunakan yaitu P1= 4800 mg/kgbb/hari, P2=7200 mg/kgbb/hari dan P3= 9600 mg/kgbb/hari diberikan peroral sebanyak dua siklus epitel seminiferus. Analisa dengan uji Anova dengan derajat kepercayaan 95% dan jika bermakna dilanjutkan dengan uji Multiple Comparissons jenis

FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer.

Science.gov (United States)

Bhartiya, Deepa; Singh, Jarnail

2015-01-01

Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers. © 2015 Society for Reproduction and Fertility.

Recovery of ovarian function after postradiation menopause. Do FSH levels have a definitive prognostic value?

International Nuclear Information System (INIS)

Letur-Konirsch, H.; Guis, F.

1996-01-01

Menopause, conventionally defined as the permanent cessation as a result of loss of ovarian follicular activity, is biologically expressed by the collapse of plasma levels and increased plasma levels of the gonadotrophins FSH (follicle stimulating hormone) and LH (luteinizing hormone). At present, estimation of the ovarian follicle reserve is based on endocrine capacity tests of the ovaries, with increased FSH representing the first sign of exocrine ovarian failure. We report the case of one of our amenorrhoeic patients after chemotherapy, total body radiation and allogeneic bone marrow transplantation for acute immuno-blastic leukaemia. This patient was included in an in vitro fertilization with oocyte donation (IVF-OD) programme for iatrogenic premature ovarian failure with increased FSH levels. Instead of high levels of gonadotrophins, this young woman recovered spontaneous follicular developments, benefited from standard IVF with her own oocytes and brought a twin pregnancy to term. This observation shows that a high FSH level is not a definitive prediction of ovarian exocrine capacity. In young women of child-bearing age such as these wanting a child and showing signs of endogenous estrogen impregnation, evaluation of the existence and quality of follicular development is an important factor. (author)

FSH inhibits the augmentation by oestradiol of the pituitary responsiveness to GnRH in the female rat

NARCIS (Netherlands)

Schuiling, GA; Valkhof, N; Koiter, TR

The effect of follicle stimulating hormone (FSH) treatment on the pituitary response to gonadotrophin-releasing hormone (GnRH) was studied in rats in various reproductive conditions. A 3-day treatment of cycling rats with FSH (Metrodin(R); 10 IU/injection) lowered the spontaneous pre-ovulatory

Recombinant LH supplementation to recombinant FSH during the final days of controlled ovarian stimulation for in vitro fertilization. A multicentre, prospective, randomized, controlled trial

DEFF Research Database (Denmark)

Nyboeandersen, A.; Humaidan, P.; Fried, G.

2008-01-01

BACKGROUND: The purpose of this multicentre, multinational trial was to study whether rLH supplementation to recombinant FSH (rFSH) during the late follicular phase increased pregnancy rates. METHODS: After down-regulation with nafarelin, 526 women were randomized on Day 1 of stimulation to use...... either rFSH (Gonal-F) alone (n = 261) or to continue after Day 6 of stimulation with both rFSH (Gonal-F) and rLH (Luveris) (n = 265) from Day 6. The starting dose of rFSH was 150-225 IU/day according to age below or above 35 years. RESULTS: Ongoing pregnancy rate at week 10-12 was 28.7% after rFSH alone...... and 27.2% after rFSH + rLH. This showed no evidence of a difference. Administration of rLH significantly (Prates in patients with low LH levels (

Recombinant LH supplementation to recombinant FSH during the final days of controlled ovarian stimulation for in vitro fertilization. A multicentre, prospective, randomized, controlled trial

DEFF Research Database (Denmark)

Nyboeandersen, A; Al Humaidan, Peter Samir Heskjær; Fried, G

2008-01-01

BACKGROUND: The purpose of this multicentre, multinational trial was to study whether rLH supplementation to recombinant FSH (rFSH) during the late follicular phase increased pregnancy rates. METHODS: After down-regulation with nafarelin, 526 women were randomized on Day 1 of stimulation to use...... either rFSH (Gonal-F) alone (n = 261) or to continue after Day 6 of stimulation with both rFSH (Gonal-F) and rLH (Luveris) (n = 265) from Day 6. The starting dose of rFSH was 150-225 IU/day according to age below or above 35 years. RESULTS: Ongoing pregnancy rate at week 10-12 was 28.7% after rFSH alone...... and 27.2% after rFSH + rLH. This showed no evidence of a difference. Administration of rLH significantly (PLH. Ongoing pregnancy rates in patients with low LH levels (

The Effects of Trifluralin on LH, FSH and Testosterone Hormone Levels and Testis Histological Changes in Adult Rats

Directory of Open Access Journals (Sweden)

Mehrdad Shariati

2008-01-01

Full Text Available Background: Trifluralin is a herbicide and used in agriculture widely. It enters plants throughdeveloping roots and stops plant cells from division and elongation (meristemic inhibitor.Extensive application of trifluralin to control annual grasses and broadleaf weeds in agriculture,horticulture and horn garden, leads to environmental pollution and its entrance into the food chaincould have determined effects on human and other species. In this research the effects of trifluralinon reproductive parameters of the male rats including serum luteinizing hormone (LH, folliclestimulatinghormone (FSH, testosterone levels, and changes in testicular tissue and body weightwere investigated.Materials and Methods: For this purpose male rats were randomly divided in 5 groups, to includecontrol, sham (received normal saline as a solvent, and three experimental groups which received500, 1000 and 2000 mg/kg oral trifluralin respectively. After 16 days, body and testis weight weremeasured and blood samples were taken from heart and used for measurement of LH, FSH andtestosterone levels. To evaluate histological changes, testes were removed and weighed and, afterobtaining tissue section, stained by HE.Results: Serum testosterone, FSH, and LH levels showed significant decrease in experimentalgroups (p<0.05. There was significant decrease in the number of germinal and somatic cells intestis in experimental groups. There was also a significant decrease in body and testis weight inexperimental groups.Conclusion: It can be concluded that oral administration of trifluralin could decrease gonadotropinsand testosterone hormone levels and also this herbicide could have hazardous effects on testistissue.

Recombinant FSH in alternative doses or versus urinary gonadotrophins for ovulation induction in subfertility associated with polycystic ovary syndrome: a systematic review based on a Cochrane review

NARCIS (Netherlands)

van Wely, M.; Bayram, N.; van der Veen, F.

2003-01-01

This systematic review was performed to study the efficacy and safety of recombinant FSH (rFSH) versus urinary FSH (uFSH) and to compare different dose regimens of rFSH for ovulation induction in women with clomiphene-resistant polycystic ovary syndrome (PCOS). Six randomized controlled trials were

Radioimmunoassay of follicle stimulating hornone in human plasma

International Nuclear Information System (INIS)

Akande, E.O.

1976-01-01

A radioimmunoassay method for Follicle Stimulating Hormone (fsh) in human plasma is described. The method proved to be reliable in determining fsh levels in normally menstruating women as well as women in varying clinical states. The patterns and levels of fsh obtained from 16 menstrual cycles in 12 normally menstruating women showed agreement with previous results of Franchimont, Faiman and Ryan, etc

Expression of FSH receptor in ovary tissue of rats with letrozole-induced polycystic ovary syndrome

International Nuclear Information System (INIS)

Guo Hongsheng; An Changxin; Chen Dong

2009-01-01

Objective: To investigate the expressions of FSH receptor mRNA and protein in ovary tissue in rats with letrozole-induced polycystic ovary syndrome (PCOS), and to provide experimental data for the model application. Methods: Forty rats were randomly divided into two groups (n=20), in PCOS model group letrozole was administered once daily during 21 d, and in control group without any treatment. The gonadal hormone concentrations in serum were determined by radioimmunoassay, the histologic changes in ovaries were observed by HE staining, the expression of FSH receptor gene in ovary tissue was detected by realtime -PCR, Western blotting and immunohistochemistry. Results: Compared with control group, estradiol (E 2 ) and progesterone in model group showed a considerable reduction (P 0.05). Compared with control group, the ovaries from model group showed high incidence of subcapsular ovarian cyst and capsular thickening and decreased number of corpora lute a. The expressions of FSH receptor mRNA and protein were significantly higher in model group than those in control group (P<0.05). Conclusion: The expression of FSH receptor gene in letrozole-induced polycystic ovaries is similar with that of PCOS women, the rat model is proved to be an ideal PCOS animal model to study the pathophysiology of PCOS. (authors)

The effect of follicular fluid hormones on oocyte recovery after ovarian stimulation: FSH level predicts oocyte recovery

Directory of Open Access Journals (Sweden)

Rinaudo Paolo F

2009-04-01

Full Text Available Abstract Background Ovarian stimulation for assisted reproductive technology (ART overcomes the physiologic process to develop a single dominant follicle. However, following stimulation, egg recovery rates are not 100%. The objective of this study is to determine if the follicular fluid hormonal environment is associated with oocyte recovery. Methods This is a prospective study involving patients undergoing ART by standard ovarian stimulation protocols at an urban academic medical center. A total of 143 follicular fluid aspirates were collected from 80 patients. Concentrations of FSH, hCG, estradiol, progesterone, testosterone and prolactin were determined. A multivariable regression analysis was used to investigate the relationship between the follicular fluid hormones and oocyte recovery. Results Intrafollicular FSH was significantly associated with oocyte recovery after adjustment for hCG (Adjusted odds ratio (AOR = 1.21, 95%CI 1.03–1.42. The hCG concentration alone, in the range tested, did not impact the odds of oocyte recovery (AOR = 0.99, 95%CI 0.93–1.07. Estradiol was significantly associated with oocyte recovery (AOR = 0.98, 95% CI 0.96–0.99. After adjustment for progesterone, the strength of association between FSH and oocyte recovery increased (AOR = 1.84, 95%CI 1.45–2.34. Conclusion The relationship between FSH and oocyte recovery is significant and appears to work through mechanisms independent of the sex hormones. FSH may be important for the physiologic event of separation of the cumulus-oocyte complex from the follicle wall, thereby influencing oocyte recovery. Current methods for inducing the final stages of oocyte maturation, with hCG administration alone, may not be optimal. Modifications of treatment protocols utilizing additional FSH may enhance oocyte recovery.

Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis.

Science.gov (United States)

Kuo, Shih-Wei; Ke, Ferng-Chun; Chang, Geen-Dong; Lee, Ming-Ting; Hwang, Jiuan-Jiuan

2011-06-01

Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. Copyright © 2010 Wiley-Liss, Inc.

Normal levels of plasma FSH and LH in the menstrual cycle as determined by radioimmunoassay

International Nuclear Information System (INIS)

Lemgruber, I.; Pinto, J.C.M.; Linhares, E.; Granafer, A.

1981-01-01

The biological methods were not able to establish adequately the separate determination of FSH and LH. The introduction of radioimmunoassay had allowed the identification of plasma FSH and LH for the purpose of routine clinical use. The utilization of commercial kits, however, obliges each laboratory to have normal levels of his own. Such is the finality of this work, studying samples from 200 normal women, hospitalized for surgical reasons and having not any endocrinological problem. (author) [pt

An economic comparison of a laparoscopic electrocautery strategy and ovulation induction with recombinant FSH in women with clomiphene citrate-resistant polycystic ovary syndrome

NARCIS (Netherlands)

van Wely, M.; Bayram, N.; van der Veen, F.; Bossuyt, P. M. M.

2004-01-01

BACKGROUND: Recombinant FSH (rFSH) is the current standard treatment for ovulation induction in women with polycystic ovary syndrome (PCOS) that do not respond to clomiphene citrate. Ovulation induction with rFSH is known to be costly due to the necessity of daily injections and intensive

Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients

DEFF Research Database (Denmark)

Polyzos, Nikolaos P; Devos, Michel; Humaidan, Peter

2013-01-01

OBJECTIVE: To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH antagonist protocol. DESIGN: Retrospective pilot study. SETTING: University-based tertiary care center. PATIENT(S): Poor ovarian responders fulfilling the Bologna criteria...... developed by European Society for Human Reproduction and Embryology Consensus Group. INTERVENTION(S): Corifollitropin alfa (150 μg) followed by 300 IU rFSH in a GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Endocrinologic profile and ongoing pregnancy rates. RESULT(S): Among 43 women treated...

Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

Science.gov (United States)

Souza, Priscila Morais Galvão; Carvalho, Bruno Ramalho de; Nakagawa, Hitomi Miura; Rassi, Thalita Reis Esselin; Barbosa, Antônio César Paes; Silva, Adelino Amaral

2017-06-01

This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged 0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.

Immunodetection of Luteinizing Hormone (LH, Follicle-Stimulating Hormone (FSH, Thyroid Stimulating Hormone (TSH and Prolactin (PRL in Brachionus calyciflorus (Rotifera: Monogononta

Directory of Open Access Journals (Sweden)

Jesús Alvarado-Flores

2009-12-01

Full Text Available The endocrine system controls and coordinates behavioral, biochemical, and physiological processes through signal mechanisms using neuropeptides or products of neurosecretory cells. Among invertebrates, this system is poorly studied in rotifers, in which estrogens and androgens significantly affect sexual reproduction. This is the first report of the presence of the Luteinizing Hormone (LH, Follicle-Stimulating Hormone (FSH, Thyroid Stimulating Hormone (TSH and Prolactin (PRL in rotifers. Analyses included the avidin-biotin-peroxidase complex method with primary antibodies LH (Anti-Rat LH serum for RIA, PRL (Anti-Rat PRL serum for RIA, FSH (Anti-Rat FSH serum for RIA and TSH (Anti-Rat TSH serum for RIA. These hormones were found in females, males and parthenogenetic and sexual eggs of the freshwater Brachionus calyciflorus. The immunoreactivity of FSH, LH, TSH and PRL in females was observed in: ovaries, cerebrum, mastax, stomach, lorica, and the stomach gland. However, in males LH was observed only at the trochal disk and cerebrum. The hormones FSH, TSH and PRL, were observed in testicles, contractil vesicles, and cementary gland of males. Regarding amictic or parthenogenetic eggs, the hormones LH, FSH, TSH, and PRL were located mainly in the micromeres, and the staining in the macromeres was weak. On the other hand, in the mictic or sexual eggs the inner shell is stained for the hormones PRL and LH, opposite to the staining of FSH and TSH, located mainly in the embryo. In general, immuno-reactivity was observed in areas important for the reproductive, excretory, digestive and developmental processes. Rev. Biol. Trop. 57 (4: 1049-1058. Epub 2009 December 01.Se logró detectar la presencia de las hormonas: Hormona Luteinizante (LH, Hormona Folículo Estimulante (FSH, Hormona Estimulante de la Tiroides (TSH y Prolactina (PRL en Brachionus calyciflorus siendo el primer reporte de la presencia de dichas hormonas en rotíferos. Estas hormonas fueron

Inhibition of iodine-125-labeled human follitropin binding to testicular receptor by epidermal growth factor and synthetic peptides

International Nuclear Information System (INIS)

Sluss, P.M.; Krystek, S.R. Jr.; Andersen, T.T.; Melson, B.E.; Huston, J.S.; Ridge, R.; Reichert, L.E. Jr.

1986-01-01

Two tetrapeptide sequence homologies between mouse epidermal growth factor precursor (mEGFP) and human follitropin (FSH) were revealed by a computer program that identifies identical residues among polypeptide sequences. The two tetrapeptides, Lys-Thr-Cys-Thr (KTCT) and Thr-Arg-Asp-Leu (TRDL), are present in the hormone-specific beta subunit of FSH from all species studied. These tetrapeptides are not present in the alpha subunit, which is common to all pituitary glycoprotein hormones. Both tetrapeptides are also found in mEGFP, and one tetrapeptide, TRDL, is located within the 53-residue form of mEGF purified from mouse submaxillary glands. Computer-generated hydropathy profiles predicted that both tetrapeptides are located in hydrophilic portions of the FSH beta subunit and that TRDL is in a hydrophilic portion of commercially available mEGF. Therefore, the tetrapeptides might be accessible to receptor binding sites for FSH. We report that mEGF inhibits binding of 125 I-labeled human FSH to receptors in testis by 50% (I50) at a concentration of 1.8 X 10(-5) M. No binding inhibition was observed by GnRH or arginine-vasopressin at 10(-4) M, neither of which contain the tetrapeptide sequences. FSH beta subunit, which contains both tetrapeptides, also inhibited binding (I50 = 9 X 10(-8) M) of 125 I-labeled human FSH to testis receptor. Thus, it appears that FSH beta subunit and mEGF are capable of inhibiting binding of FSH to testicular FSH receptors, presumably through interactions that include the homologous tetrapeptides. This presumption was supported by the observation that the synthetic tetrapeptides (KTCT or TRDL) were also active in inhibiting binding of 125 I-labeled human FSH to testis receptor

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

NARCIS (Netherlands)

van Tilborg, Theodora C.; Eijkemans, Marinus J. C.; Laven, Joop S. E.; Koks, Carolien A. M.; de Bruin, Jan Peter; Scheffer, Gabrielle J.; van Golde, Ron J. T.; Fleischer, Kathrin; Hoek, Annemieke; Nap, Annemiek W.; Kuchenbecker, Walter K. H.; Manger, Petra A.; Brinkhuis, Egbert A.; van Heusden, Arne M.; Sluijmer, Alexander V.; Verhoeff, Arie; van Hooff, Marcel H. A.; Friederich, Jaap; Smeenk, Jesper M. J.; Kwee, Janet; Verhoeve, Harold R.; Lambalk, Cornelis B.; Helmerhorst, Frans M.; van der Veen, Fulco; Mol, Ben Willem J.; Torrance, Helen L.; Broekmans, Frank J. M.

2012-01-01

Background: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative

Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

International Nuclear Information System (INIS)

Christman, G.M.; Randolph, J.F. Jr.; Peegel, H.; Menon, K.M.

1991-01-01

The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures

Ultrastructure of Sheep Primordial Follicles Cultured in the Presence of Indol Acetic Acid, EGF, and FSH

Directory of Open Access Journals (Sweden)

Evelyn Rabelo Andrade

2011-01-01

Full Text Available The aim of this study was to investigate the ultrastructural characteristics of primordial follicles after culturing of sheep ovarian cortical slices in the presence of indol acetic acid (IAA, Epidermal Growth Factor (EGF, and FSH. To evaluate ultrastructure of primordial follicles cultured in MEM (control or in MEM containing IAA, EGF, and FSH, fragments of cultured tissue were processes for transmission electron microscopy. Except in the control, primordial follicles cultured in supplemented media for 6 d were ultrastructurally normal. They had oocyte with intact nucleus and the cytoplasm contained heterogeneous-sized lipid droplets and numerous round or elongated mitochondria with intact parallel cristae were observed. Rough endoplasmic reticulum (RER was rarely found. The granulosa cells cytoplasm contained a great number of mitochondria and abundant RER. In conclusion, the presence of IAA, EGF, and FSH helped to maintain ultrastructural integrity of sheep primordial follicles cultured in vitro.

Dependence of serum hormones (T, FSH, LH) on morphometric testicular findings recorded from patients after chemotherapy and radiotherapy for malignant testicular tumours

International Nuclear Information System (INIS)

Barth, V.; Schoenfelder, M.

1990-01-01

Correlations which exist between morphometric parameters of remaining testicular tissue, on the one hand, and serum hormones on the other (testosterone = T, follicle-stimulating hormone = FSH, luteinising hormone = LH), depending on therapeutic action taken on patients for malignant testicular tumours, seem to suggest that decline in epithelial thickness together with increase in wall thickness leads to rise in FSH. No unambiguous relations, on the other hand, were found to exist between testosterone or luteotrophic hormone and morphometric findings. Hence, FSH seems to characterize the severity of damage to germ epithelium and thus the degree of impairment to spermatogenesis. FSH may be accepted as a criterion for fertility disorders in sexually active men. (author)

Differentially expressed miRNAs after GnRH treatment and their potential roles in FSH regulation in porcine anterior pituitary cell.

Directory of Open Access Journals (Sweden)

Rui-Song Ye

Full Text Available Hypothalamic gonadotropin-releasing hormone (GnRH is a major regulator of follicle-stimulating hormone (FSH secretion in gonadotrope cell in the anterior pituitary gland. microRNAs (miRNAs are small RNA molecules that control gene expression by imperfect binding to the 3'-untranslated region (3'-UTR of mRNA at the post-transcriptional level. It has been proven that miRNAs play an important role in hormone response and/or regulation. However, little is known about miRNAs in the regulation of FSH secretion. In this study, primary anterior pituitary cells were treated with 100 nM GnRH. The supernatant of pituitary cell was collected for FSH determination by enzyme-linked immunosorbent assay (ELISA at 3 hours and 6 hours post GnRH treatment respectively. Results revealed that GnRH significantly promoted FSH secretion at 3 h and 6 h post-treatment by 1.40-fold and 1.80-fold, respectively. FSHβ mRNA at 6 h post GnRH treatment significantly increased by 1.60-fold. At 6 hours, cells were collected for miRNA expression profile analysis using MiRCURY LNA Array and quantitative PCR (qPCR. Consequently, 21 up-regulated and 10 down-regulated miRNAs were identified, and qPCR verification of 10 randomly selected miRNAs showed a strong correlation with microarray results. Chromosome location analysis indicated that 8 miRNAs were mapped to chromosome 12 and 4 miRNAs to chromosome X. Target and pathway analysis showed that some miRNAs may be associated with GnRH regulation pathways. In addition, In-depth analysis indicated that 10 up-regulated and 3 down-regulated miRNAs probably target FSHβ mRNA 3'-UTR directly, including miR-361-3p, a highly conserved X-linked miRNA. Most importantly, functional experimental results showed that miR-361-3p was involved in FSH secretion regulation, and up-regulated miR-361-3p expression inhibited FSH secretion, while down-regulated miR-361-3p expression promoted FSH secretion in pig pituitary cell model. These differentially

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.

Science.gov (United States)

Oudshoorn, Simone C; van Tilborg, Theodora C; Eijkemans, Marinus J C; Oosterhuis, G Jur E; Friederich, Jaap; van Hooff, Marcel H A; van Santbrink, Evert J P; Brinkhuis, Egbert A; Smeenk, Jesper M J; Kwee, Janet; de Koning, Corry H; Groen, Henk; Lambalk, Cornelis B; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed. Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response. Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders. Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective. We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The

IL-6 Promotes FSH-Induced VEGF Expression Through JAK/STAT3 Signaling Pathway in Bovine Granulosa Cells

Directory of Open Access Journals (Sweden)

Meng Yang

2017-11-01

Full Text Available Background/Aims: Vascular endothelial growth factor (VEGF has been demonstrated to play a pivotal role in the regulation of angiogenesis in ovarian follicular development, particularly during the preovulatory period. Although numerous studies have shown that interleukin-6 (IL-6 is one of the major inducing factors that regulate the expression of VEGF in non-ovarian cells, whether it involved in regulating the expression of VEGF in normal ovarian granulosa cells is still unknown. The aim of this study was to elucidate the mechanisms underlying the effect of IL-6 on FSH-induced VEGF expression in bovine granulosa cells derived from large follicles. Methods: VEGF mRNA expression in granulosa cells after IL-6 with/without inhibitors treatment was analyzed by RT-qPCR. Phosphorylation levels of ERK1/2 and STAT3 proteins induced by IL-6 were analyzed by western blotting. The protein levels produced by granulosa cells were detected by ELISA. Results: High concentration of IL-6 (10ng/ml can significantly up-regulate FSH-induced VEGF gene and protein expression levels in granulosa cells, and also promote the VEGF upstream regulators HIF-1α and COX2 mRNA expression. VEGF expression levels were significantly decreased after specifically blocking HIF-1α and COX2 by using inhibitors. The up-regulation effect of IL-6 on FSH-induced VEGF expression in granulosa cells mainly through activating the JAK/STAT3 signaling pathway, which can be impaired by JAK inhibitors. Conclusion: IL-6 can promote FSH-induced VEGF expression in granulosa cells, which is mainly achieved by increasing the expression of HIF-1α and COX2.This promoting effect is mediated by activating the JAK/STAT3 pathway. Moreover, there may be a synergistic relationship between FSH and IL-6 in the regulation of VEGF expression.

Production of anti-IgG antibodies in sheep for using in the radioimmunoassays of LH, FSH and prolactin

International Nuclear Information System (INIS)

Caso, R.; Perez, E.; Mosquera, M.; Arranz, C.

1996-01-01

In this work described the production of second antibodies in sheep against rabbit IgG for being used in radioimmunoassays for determination LH, FSH and Prolactin. There was made the comparison between the results obtained using the Kits-RIA produced by us and the commercial WHO Kits-RIA, using these antibodies. The results allowed us to use these antibodies for production Kits-RIA of LH, FSH and Prolactin

Altas concentrações de FSH-p na maturação in vitro de oócitos Bos indicus High concentrations of FSH-p on the in vitro maturation of Bos indicus oocytes

Directory of Open Access Journals (Sweden)

Joana D'Arc Rocha Alves

2001-08-01

Full Text Available O objetivo deste trabalho foi avaliar a eficiência de diferentes concentrações de um FSH-p comercial sobre a maturação nuclear de oócitos Bos indicus, clivagem e desenvolvimento in vitro de embriões até estádios de blastocisto. Após seleção e transferência para o meio TCM 199/HEPES suplementado com diferentes concentrações de FSH-p (T1 = 10mg/m ; T2 = 20mg/m ; T3 = 40mg/m, os oócitos foram incubados, durante 24 horas, a 39ºC em atmosfera úmida contendo 5% de CO2. Parte dos oócitos foram retirados para análise da maturação nuclear e os demais foram transferidos para o meio de fecundação (mDM. Após 18 horas de incubação nas mesmas condições atmosféricas mencionadas para os oócitos, os presumíveis zigotos foram distribuídos no meio de desenvolvimento embrionário (KSOM contendo monocamada de células da granulosa. As porcentagens de metáfase II, de clivagem e de blastocisto foram, respectivamente, de 81,8/62,5/17,6% (T1; 55,6/64,0/19,5% (T2 e 50,0/65,0/16,3% (T3. A análise estatística revelou que uma menor porcentagem (P £ 0,05 de oócitos tratados com 20mg/m e 40mg/m de FSH-p alcançou o estádio de metáfase II e que as taxas de clivagem e blastocisto não diferiram (P ³ 0,05 entre os tratamentos. Os resultados permitem concluir que a adição de 20mg/m e 40mg/m de FSH-p ao meio de cultura interfere no processo de maturação nuclear, mas todas as concentrações testadas podem ser utilizadas sem prejuízo aparente para a clivagem e o posterior desenvolvimento embrionário.The aim of this work was to evaluate the efficiency of different concentrations of a commercial FSH-p on the nuclear maturation of Bos indicus oocytes, cleavage and in vitro development of embryos until blastocyst stages. The oocytes were selected and transferred to the maturation medium (TCM 199/25 mM HEPES supplemented with different concentrations of FSH-p (T1 = 10mg/m ; T2 - 20mg/m ; T3 - 40mg/m and after 24 hours of incubation, at 39º

Application of Magnetizable Cellulose Particles in Radioimmunoassay for In-Vitro Determination of Follicle Stimulating Hormone in Human Serum

International Nuclear Information System (INIS)

Ebeid, N.H.; El-Bayoumy, A.S.A.

2017-01-01

The measurement of Follicle Stimulating Hormone ( FSH) in human serum is essential for investigating fertility and especially disorders of the hypothalamic pituitary gonadal axis. Therefore, the present study aimed to prepare radioimmunoassay (RIA) system using solid phase magnetic particles for the in-vitro quantitative measurement of FSH in human serum. The preparation of polyclonal antibody (anti-FSH), "1"2"5I-FSH tracer and FSH standards was carried out. The activation of magnetic particles using 1, /1-carbonyl diimidazole (CDI) and coupling of activated particles with purified anti-FSH were carried out. Optimization and validation of the assay were undertaken. The reproducibility as measured by the intra-and inter-assay variations is acceptable. The recovery and dilution tests indicated accurate calibration and appropriate matrix. The present technique is in a good agreement well with the currently used commercial kit (Izotop, IRMA). The magnetic particles of the present system for estimation of FSH retain their characteristics during storage for 12 months at 4 °C. It can be concluded that this technique proved to be sensitive, specific, precise and accurate for routine laboratory use

Genetic variations altering FSH action affect circulating hormone levels as well as follicle growth in healthy peripubertal girls.

Science.gov (United States)

Busch, Alexander S; Hagen, Casper P; Almstrup, Kristian; Main, Katharina M; Juul, Anders

2016-04-01

counts, however, a cumulative minor allele count (FSHB c.-211 G>T and FSHR c.-29G>A) was negatively associated with the number of large follicles (≥5 mm) (n = 91, P = 0.04) (adjusted for Tanner stages). Since we studied girls and young adolescents during pubertal transition, our study may not be fully comparable with previous studies on FSHB and FSHR variants in adult women. The group of young adolescents (Tanner B4 + B5) reflects the endocrine situation in adult women best, however, the group is not large enough to contribute substantially to the conflicting results concerning the influence of FSHB c.-211G>T in adult women. Furthermore, we have no information about the exact day of the menstrual cycle in the subgroup of girls with menarche. The sex-specific interaction of FSHB and FSHR genetic variants and physiological as well as pathological conditions is being increasingly elucidated. The variant triplet set might serve as diagnostic and pharmacogenetic marker. For the first time, we show an additional effect of FSHR c.-29G>A on serum FSH levels in healthy girls. Moreover, morphological data suggest impaired FSH-induced maturation of ovarian follicles in minor allele carriers of FSHB c.-211G>T and FSHR c.-29G>A. This may explain previous findings of delayed pubertal onset in these girls. Funding was provided by the Danish Agency for Science, Technology and Innovation (09-067180), Danish Ministry of the Environment, CeHoS (MST-621-00065), Capital Region of Denmark (December 2011), Ministry of Higher Education and Science (DFF-1331-00113) and EDMaRC (Danish Ministry of Health). A.S.B. was funded from December 2015 by ReproUnion (EU Interreg Öresund-Kattegat-Skagerrak). The authors declare no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Increasing the Stimulation Dose of rFSH in Unexpected Poor Responders Is Not Associated with Better IVF Outcome

Directory of Open Access Journals (Sweden)

Levent Tutuncu

2012-01-01

Full Text Available The aim of this retrospective study is to determine whether increasing the stimulation dose of rFSH in unexpected poor responders is associated with better in vitro fertilization (IVF outcome or not. A total of forty eligible women who fulfilled our definition of poor responders and who did not achieve an ongoing pregnancy in the first cycle and returned for a second higher rFSH dose IVF cycle with a long-agonist protocol were included to the study. The first low-dose cycles and the second high-dose cycles were compared to each other. Main outcome measures of the study were duration of stimulation, number of follicles, number of oocytes retrieved, number of embryos, and E2 level on day of hCG injection. There were no significant differences in duration of stimulation, number of follicles, number of oocytes retrieved, number of embryos, and E2 level on day of hCG injection between the first low- and second high-dose cycles. Daily dose and total dose of rFSH were significantly higher in the second high-dose cycles. Increasing the dose of rFSH in a second stimulation cycle after first unsuccessful treatment cycle will add only to the cost and discomfort of the treatment and might adversely affect pregnancy rates.

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

Directory of Open Access Journals (Sweden)

van Tilborg Theodora C

2012-09-01

Full Text Available Abstract Background Costs of in vitro fertilisation (IVF are high, which is partly due to the use of follicle stimulating hormone (FSH. FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT. The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT is more cost-effective than a standard dose regime. Methods/Design Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged  Discussion The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. Trial registration NTR2657

Effect of different dose rates administration of FSH + LH (Pergonal®)

African Journals Online (AJOL)

The does were randomly assigned to 4 treatment groups administered of 19.0 IU, 38.0 IU and 76.0 IU FSH + LH (Pergonal®) and 1.0 ml physiological saline as the control treatment. The treatments were administered intramuscularly for 3 days consecutively. The results on the number of corpora lutea on the ovary did not ...

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial.

Science.gov (United States)

van Tilborg, Theodora C; Eijkemans, Marinus J C; Laven, Joop S E; Koks, Carolien A M; de Bruin, Jan Peter; Scheffer, Gabrielle J; van Golde, Ron J T; Fleischer, Kathrin; Hoek, Annemieke; Nap, Annemiek W; Kuchenbecker, Walter K H; Manger, Petra A; Brinkhuis, Egbert A; van Heusden, Arne M; Sluijmer, Alexander V; Verhoeff, Arie; van Hooff, Marcel H A; Friederich, Jaap; Smeenk, Jesper M J; Kwee, Janet; Verhoeve, Harold R; Lambalk, Cornelis B; Helmerhorst, Frans M; van der Veen, Fulco; Mol, Ben Willem J; Torrance, Helen L; Broekmans, Frank J M

2012-09-18

Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy

Conversion of human choriogonadotropin into a follitropin by protein engineering

International Nuclear Information System (INIS)

Campbell, R.K.; Dean-Emig, D.M.; Moyle, W.R.

1991-01-01

Human reproduction is dependent upon the action of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the α subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their β subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG β-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLHβ and hFSHβ in receptor recognition and activation. Since the β subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region, the authors postulated that these residues might contribute to hormone specificity. To test this hypothesis the authors constructed chimeric hCG/hFSH β subunits, coexpressed them with the human α subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSHβ residues 33-52 for hCGβ residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSHβ residues 88-108 in place of the carboxyl terminus of hCGβ (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCGβ residues 108-145 or substitution of residues in the determinant loop located between hCDβ residues 93 and 100

Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse pituitary gland.

Science.gov (United States)

Miyano, Yuki; Tahara, Shigeyuki; Sakata, Ichiro; Sakai, Takafumi; Abe, Hiroyuki; Kimura, Shioko; Kurotani, Reiko

2014-04-01

Secretoglobin (SCGB) 3A2 was originally identified as a downstream target for the homeodomain transcription factor NKX2-1 in the lung. NKX2-1 plays a role in the genesis and expression of genes in the thyroid, lung and ventral forebrain; Nkx2-1-null mice have no thyroid and pituitary and severely hypoplastic lungs and hypothalamus. To demonstrate whether SCGB3A2 plays any role in pituitary hormone production, NKX2-1 and SCGB3A2 expression in the mouse pituitary gland was examined by immunohistochemical analysis and RT-PCR. NKX2-1 was localized in the posterior pituitary lobe, whereas SCGB3A2 was observed in both anterior and posterior lobes as shown by immunohistochemistry and RT-PCR. Expression of CCAAT-enhancer binding proteins (C/EBPs), which regulate mouse Scgb3a2 transcription, was also examined by RT-PCR. C/EBPβ, γ, δ and ζ were expressed in the adult mouse pituitary gland. SCGB3A2 was expressed in the anterior and posterior lobes from postnatal days 1 and 5, respectively and the areas where SCGB3A2 expression was found coincided with the area where FSH-secreting cells were found. Double-staining for SCGB3A2 and pituitary hormones revealed that SCGB3A2 was mainly localized in gonadotrophs in 49 % of FSH-secreting cells and 47 % of LH-secreting cells. In addition, SCGB3A2 dramatically inhibited LH and FSH mRNA expression in rat pituitary primary cell cultures. These results suggest that SCGB3A2 regulates FSH/LH production in the anterior pituitary lobe and that transcription factors other than NKX2-1 may regulate SCGB3A2 expression.

Measurement Differences Between Two Immunoassay Systems for LH and FSH: A Comparison of Roche Cobas e601 vs. Abbott Architect i2000sr.

Science.gov (United States)

Yin, Lianli; Tang, Yinghua; Chen, Xiang; Sun, Yifan

2018-03-01

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) regulate the growth and reproductive activity of gonadal tissue and determine the concentration of LH is essential for the prediction of ovulation. Collectively, FSH and LH are important measurements to ascertain the causes of infertility as well as diagnosing disorders such as polycystic ovary syndrome and pituitary and gonadal dysfunction. This study compares the correlation between LH and FSH measurements during examination with two different systems, Architect i2000sr (Abbott Laboratories; Lake Bluff, IL, USA) and Cobas e601 (Roche; Geneva, Switzerland), and assesses the differences between these systems. Serum analysis was performed for 95 patients using both the Cobas e601 and Architect i2000sr systems. The method used to compare the systems was Passing-Bablok regression analysis with a Bland-Altman agreement plot. Inter-rater agreement was analyzed using a concordance correlation coefficient. Architect i2000sr and Cobas e601 have strong correlations in their LH and FSH results. However, the Bland-Altman plot shows that LH and FSH measurements in Cobas e601 are about 1.31 times and 1.26 times higher than those in Architect i2000sr, respectively. Passing-Bablok regression analysis also shows significant proportional deviation between them. The difference between the test results for LH and FSH in Cobas e601 and Architect i2000sr indicate that the results from one system cannot be directly used to evaluate the other system.

Evaluation of the double antibody - solid phase radioimmunoassay technique in plasma LH and FSH and urinary LH measurements

International Nuclear Information System (INIS)

Karonen, S.-L.; Laehteenmaeki, P.; Hohenthal, U.; Adlercreutz, H.

1978-01-01

Double antibody phase (DASP) radioimmunoassay methods for plasma LH and FSH and urinary LH were developed and carefully evaluated as to their reliability and practicability. The peptide hormones were iodinated enzymatically with immobilized lactoperoxidase which resulted in pure and stable products of unchanged immunoreactivity. The sensitivities of these assay methods are 0.02, 0.17 and 0.20 mlU/tube for plasma LH (MRC 68/40) and FSH (MRC 68/39) and urinary LH (IRP-HMG, urinary), respectively. Interassay coefficients of variation obtained over a 6-18 month period were 14.2, 14.7 and 12.8%, respectively. The latter values for plasma LH and FSH assays were obtained from one level pool samples, and the value for urinary LH is the mean of those obtained from two pools of different levels. Plasma reference values for LH and FSH obtained using these methods are about 1.8-2.9 times higher than those cited for other types of radioimmunoassay. However, the values obtained for LH in urine are similar to those reported in the literature. It is suggested that the DASP technique is less influenced by interference from plasma proteins and because of this gives plasma values closer to the true ones. It is concluded that the methods are well suited for use as routine clinical assays in laboratories with a high work load. (Auth.)

Body mass index and gonadotropin hormones (LH & FSH) associate with clinical symptoms among women with polycystic ovary syndrome.

Science.gov (United States)

Esmaeilzadeh, Seddigheh; Andarieh, Maryam Ghanbari; Ghadimi, Reza; Delavar, Mouloud Agajani

2014-09-28

To evaluate the relevance of body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and LH/FSH ratio with clinical symptoms in polycystic ovary syndrome (PCOS) women. We reviewed the medical records of all women visited in the PCOS Clinic of Babol (Iran) from 2008 to 2012. A retrospective cross-sectional study was conducted on 175 PCOS women; aged 18-38 years diagnosed based on the Rotterdam criteria. Among the PCOs women, the prevalence of oligomenorrhea, acne, and hirsutism were found to be 92.0%, 31.4%, and 78.9%, respectively. Positive finding of polycystic ovaries was observed in 89.1% of PCOS women with by using sonography. A total of 69.2% overweight/obesity patients had polycystic ovary morphology on ultrasound image. Compared with non- overweight/obesity, the adjusted OR of PCOS women for sonographic view of polycystic ovaries was 4.33 (95% CI, 1.42-13.15, p=0.001), Nevertheless, the adjusted odds ratio (OR) showed no significant associations between LH, FSH, and LH/FSH ratio with clinical symptoms in these women. The findings of this study indicated that the overweight/obese women with PCOS are at an increased risk for sonographic view of polycystic ovaries. Therefore, it is suggested that successful weight loss is the most effective method of restoring ovulation, menstruation that should be used as major advice in obese PCOS patients.

Recombinant FSH Compared to Clomiphene Citrate as the First-Line in Ovulation Induction in Polycystic Ovary Syndrome Using Newly Designed Pens: A Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Batool Hossein-Rashidi

2016-05-01

Full Text Available Objective: Since there is still controversy regarding the best first-line choice for ovulation induction (OI other than clomiphene citrate (CC in infertile women diagnosed with polycystic ovary syndrome (PCOS, the aim of the present study was to compare recombinant human FSH with CC as the first course of OI in these women.Materials and methods: In this pilot randomized controlled trial, 104 infertile women diagnosed with PCOS were randomized in two groups to receive either CC with the dose of 100mg per day from day 3 of a spontaneous or progestin-induced menstruation for 5 days or rFSH with the starting dose of 50 IU daily {and weekly dose increment of as low as 12.5 IU}, on the day4 of the cycle. They were assessed during a single OI course. The pregnancy rate (PR and live birth rate (LBR were the primary outcomes. The follicular response, endometrial thickness, cancellation of the cycles and ovarian hyper stimulation (OHSS rate were the secondary outcomes.Results: Analyzing data of 96 patients using Chi2 and Fischer’s Exact test (44 in rFSH group and 52 in CC group, both PR and LBR were comparable in the two groups {13.6% vs. 9.6% and 11.4% vs. 9.6% respectively}, with the difference not to be significant (p > 0.05. No cases of OHSS or multiple gestations happened during the treatment course.Conclusion: It seems that rFSH is as efficacious as CC while not with more complications for the first-line OI in infertile women with PCOS. However, due to the limitations of the present study including the small population and the single cycle of treatment, our results did not come out to prove this and more studies with larger study population are needed to compare the cumulative PR and LBR.

Individualized versus standard FSH dosing in women starting IVF/ICSI: An RCT. Part 2: The predicted hyper responder

OpenAIRE

Oudshoorn, Simone C.; Van Tilborg, Theodora C.; Eijkemans, Marinus J. C.; Oosterhuis, G. Jur E.; Friederich, Jaap; van Hooff, Marcel H. A.; van Santbrink, Evert J. P.; Brinkhuis, Egbert A.; Smeenk, Jesper M. J.; Kwee, Janet; de Koning, Corry H.; Groen, Henk; Lambalk, Cornelis B.; Mol, Ben Willem J.; Broekmans, Frank J. M.

2017-01-01

STUDY QUESTION: Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? SUMMARY ANSWER: Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrom...

In vitro growth and maturation of isolated caprine preantral follicles: Influence of insulin and FSH concentration, culture dish, coculture, and oocyte size on meiotic resumption.

Science.gov (United States)

Silva, G M; Brito, I R; Sales, A D; Aguiar, F L N; Duarte, A B G; Araújo, V R; Vieira, L A; Magalhães-Padilha, D M; Lima, L F; Alves, B G; Silveira, L B R; Lo Turco, E G; Rodrigues, A P; Campello, C C; Wheeler, M B; Figueiredo, J R

2017-03-01

The aims of this study were: (1) to evaluate the effect of different insulin concentrations, alone or in combination with either a fixed FSH concentration or increasing FSH concentrations on the in vitro culture of isolated caprine preantral follicles and (2) to analyze the efficiency of two IVM media and maturation culture systems (with or without coculture with in vivo grown oocytes) on the meiosis resumption. Secondary follicles were cultured for 18 days in a basic medium supplemented with low- or high-insulin concentration alone or with a fixed FSH concentration or with increasing FSH concentrations. Oocytes grown in vivo or in vitro were matured alone or cocultured. The high-insulin concentration associated with fixed FSH treatment had higher meiotic resumption rate (P media. In conclusion, a basic medium supplemented with 10-μg/mL insulin and 100-μg/mL FSH throughout the culture period improved meiotic resumption rate and produced MII oocytes from caprine preantral follicles cultured in vitro. The MII rate was similar between in vivo and in vitro grown oocytes ≥110 μm. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of different ranges of LH:FSH ratios in polycystic ovarian syndrome (PCOS) - Clinical based case control study.

Science.gov (United States)

Malini, N A; Roy George, K

2018-05-01

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder among reproductive aged women, leading to infertility. One of the common clinical manifestations in PCOS is that there is a difference in the range of LH production in different case of PCOS and accordingly variability in LH:FSH ratio was observed. The aim of the present study was to evaluate different ranges of LH:FSH ratios in PCOS. In this cross sectional study, a consecutive series of 745 women (aged 28.11 ± 0.2) who were subjected to infertility treatment at specialist infertility clinics in central Travancore region were considered. About 50 healthy females (aged 27.58 ± 0.4) with regular menstrual cycles were regarded as control. The data were collected from hospital records using subject's written informed consent. PCOS patients were observed to have different ranges of LH:FSH ratios from PCOS. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression of progesterone receptor protein in the ovine uterus during the estrous cycle: Effects of nutrition, arginine and FSH.

Science.gov (United States)

Grazul-Bilska, Anna T; Thammasiri, Jiratti; Kraisoon, Aree; Reyaz, Arshi; Bass, Casie S; Kaminski, Samantha L; Navanukraw, Chainarong; Redmer, Dale A

2018-03-01

To evaluate expression of progesterone receptor (PGR) AB in follicle stimulating hormone (FSH)-treated or non-treated sheep administered with arginine (Arg) or saline (Sal) fed a control (C), excess (O) or restricted (U) diet, uterine tissues were collected at the early, mid and/or late luteal phases. In exp. 1, ewes from each diet were randomly assigned to one of two treatments, Arg or Sal administration three times daily from day 0 of the first estrous cycle until uterine tissue collection. In exp. 2, ewes were injected twice daily with FSH on days 13-15 of the first estrous cycle. Uterine tissues were immunostained to detect PGR followed by image analysis. PGR were detected in luminal epithelium (LE), endometrial glands (EG), endometrial stroma (ES), myometrium (Myo), and endometrial and myometrial blood vessels. The percentage of PR-positive cells and/or intensity of staining were affected by phase of the estrous cycle, plane of nutrition, and/or FSH but not by Arg. In exp. 1, percentage of PGR-positive cells in LE and EG but not in ES and Myo was greater at the early and mid than late luteal phase, was not affected by plane of nutrition, and was similar in LE and EG. Intensity of staining was affected by phase of the estrous cycle and plane of nutrition in LE, EG and Myo, and was the greatest in LE, less in EG, and least in ES and Myo. In exp. 2, percentage of PGR-positive cells in LE, EG, ES and Myo was affected by phase of the estrous cycle, but not by plane of nutrition; was greater at the early than mid luteal phase; and was greatest in LE and EG, less in luminal (superficial) ES and Myo and least in deep ES. Intensity of staining was affected by phase of the estrous cycle and plane of nutrition in all compartments but ES, and was the greatest in LE and luminal EG, less in deep EG, and least in ES and Myo. Comparison of data for FSH (superovulated) and Sal-treated (non-superovulated) ewes demonstrated that FSH affected PR expression in all evaluated

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

Science.gov (United States)

Fragoulakis, Vassilis; Pescott, Chris P; Smeenk, Jesper M J; van Santbrink, Evert J P; Oosterhuis, G Jur E; Broekmans, Frank J M; Maniadakis, Nikos

2016-12-01

Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F ® ) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur ® ) and urinary follicle-stimulating hormone (uFSH, Fostimon ® )-for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands. A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the

Ultrasonic study of ovarian morphology in patients with hypergonadotropic amenorrhea relationship with serum FSH, LH, E2 levels

International Nuclear Information System (INIS)

Zhao Jinping; Xiang Hong; Zhou Chunmin

2004-01-01

Objective: To study the morphologic changes of ovary with transvaginal ultrasonography in patients with hypergonadotropic amenorrhea as well as the relationship between the type of ovary and serum FSH, LH, E 2 levels. Methods: Transvaginal ultrasonic examination of ovary was performed in 38 patients with hypergonadotropic amenorrhea and 36 controls, serum levels of FSH, LH, E 2 were simultaneously determined with RIA. Results: Morphologically, all the 38 pairs of ovaries in the patients were significantly smaller than those in the controls (as represented by the transverse diameter and antero-posterior diameter, P 2 levels in these two type of patients were not much different, but the mean ovarian size in the small follicular type was significantly larger than that in the non-follicular type (P<0.01). Conclusion: Transvaginal ultrasonography is very helpful for the differential diagnosis of the type of ovary in patients with hypergonadotropic amenorrhea, providing guidelines for therapy. The accuracy is even superior to that by laparoscopic biopsy. In this study, the serum FSH level is not diagnostic. (authors)

PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome.

Science.gov (United States)

Yovich, John L; Alsbjerg, Birgit; Conceicao, Jason L; Hinchliffe, Peter M; Keane, Kevin N

2016-01-01

The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH) dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Müllerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting ≤15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women algorithms in our clinic meant that the starting dose was not altered for 79.1% of patients and for 30.1% of those receiving the very lowest rFSH dosages (≤75 IU). Only 0.3% patients were diagnosed with severe ovarian hyperstimulation syndrome, all deemed avoidable due to definable breaches from the protocols. The live birth productivity rates exceeded 50% for women algorithms led to only 11.6% of women generating >15 oocytes, significantly lower than recently published data applying conventional dosages (38.2%; Palgorithms to each other, the outcomes were mainly comparable for

Use of purified FSH and LH for embryo production, cryopreservation by conventional freezing or vitrification and transfer of embryos in dairy ewes

Directory of Open Access Journals (Sweden)

Giovanni Martemucci

2010-01-01

Full Text Available Three experiments were carried out with the aim of evaluating the efficiency of techniques of in vivo production, storageand transfer of embryos in dairy sheep. Experiment I - For embryo production, thirty-one ewes were synchronized withFGA (vaginal sponges, 40 mg, 9 d and PGF2α (ICI; 50 μg, 7th d, and subdivided into three groups corresponding to thefollowing superovulatory treatments over 3 days with purified gonadotrophic preparations: A control, FSH/LH ratio = 1(250 IU p-FSH : 250 UI p-LH; B FSH/LH ratio = 2 (250 IU p-FSH : 125 IU p-LH and daily FSH/LH ratio of 3.4 – 1.7 –0.8 in the 3 days of treatment, respectively; C FSH/LH ratio = 2 (250 IU p-FSH : 125 IU p-LH and daily FSH/LH ratioof 5.0 – 1.0 – 0.3. On the 7th day after oestrus and mating, ovarian response and embryo production were evaluated.Experiment II – Three freezing methods were evaluated based upon post-thaw embryo quality: CF conventional slowfreezing by 1.5 M ethylene glycol (EG; V-1 one-step vitrification based on exposure of the embryos to one solution (EG7.15 M + ficoll 2.5 mM; V-3 vitrification in three steps, corresponding to three solutions at increasing concentration ofglycerol (GLY and EG (GLY 1.4 M; GLY 3.4 M + EG 1.4 M; GLY 4.6 M + EG 3.4 M. V-1 and V-3 frozen embryos weredirectly plunged in liquid nitrogen. At thawing, embryo viability was evaluated on the basis of morphological features.Experiment III – For embryo transfer, a total of 26 recipient ewes were synchronized with donors. On the 7th d fromoestrus, 11 recipient ewes received fresh embryos (Group FE – control and 15 recipients received vitrified-thawedembryos (Group VTE. Each recipient received 2 embryos. Superovulatory treatment B significantly advanced the onsetof oestrus compared to the control (27.3 vs 34.7 h; P10.8. Transferable embryos in Group B (7.2 resulted similar to Group A (5.3 and significantly (Pcompared to Group C (3.2. V3-method resulted in the highest (PCF- and V1-methods

Onset of lipoprotein-supported steroidogenesis in differentiating granulosa cells of rats: cellular events involved in mediating FSH-enhanced uptake of low-density lipoproteins

International Nuclear Information System (INIS)

Foster, J.D.

1987-01-01

Luteal cells use lipoproteins as the main source of cholesterol in steroidogenesis. However, little is known about the mechanisms underlying hormonal control of lipoprotein uptake. Thus, the authors tested the hypothesis that FSH and androgens regulate low density lipoprotein (LDL)-supported steroidogenesis in maturing granulosa cells by affecting receptor-mediated endocytosis of LDL at a cellular level. For this, immature ovarian granulosa cells were cultured with or without hormones, compactin (de novo synthesis inhibitor), or unlabeled or labeled ( 125 I or gold particles) LDL. Nonhormone-treated cultures produced little progestin; FSH and FSH/androstenedione stimulated steroid secretion. Progestin production by hormone-, but not nonhormone-, treated cultures was decreased by compactin, suggesting that de novo synthesis provided sterol for steroidogenesis. EM quantitation of cells exposed to gold-LDL at 37 0 C revealed that, compared to nonhormone-treated cells, FSH-treated cells (1) bound and internalized more gold-LDL, (2) had a smaller percentage of gold-LDL at their surfaces, (3) displayed a faster apparent rate of LDL internalization and delivery to lysosomes, and (4) contained more gold-labeled lysosomes. Data from biochemical studies in which 125 I-LDL was used supported the morphological findings. In conclusion, this study demonstrates that FSH has important effects at the cellular level on LDL uptake, which seem to underlie the striking increase in progestin production accompanying granulosa cell differentiation

Avaliação dos efeitos do estradiol e do FSH nos níveis de leptina em mulheres com supressão da função hipofisária Effects of estradiol and FSH on leptin levels in women with pituitary suppression

Directory of Open Access Journals (Sweden)

Selmo Geber

2005-04-01

Full Text Available OBJETIVO: identificar a correlação entre os níveis séricos de leptina e os níveis de estradiol e do hormônio folículo-estimulante (FSH em mulheres com supressão da função hipofisária, e suas possíveis interferências no eixo reprodutivo. MÉTODOS: estudamos prospectivamente 64 pacientes submetidas à hiperestimulação ovariana controlada com FSH recombinante para tratamento pela técnica de reprodução assistida, devido a fator masculino ou tubário, e 20 pacientes em uso de valerato de estradiol, para preparo endometrial, em tratamento de doação de óvulos, por falha de resposta ovariana em ciclo prévio. Todas as pacientes utilizaram análogo de GnRH no início do tratamento, de forma a obter a supressão da função hipofisária. Para a análise estatística dos resultados, foram utilizados os testes chi2, t de Student e correlação de Pearson, quando adequado. Os resultados foram considerados significativos quando pPURPOSE: to identify the relationship between serum levels of leptin and the levels of estradiol and follicle-stimulating hormone (FSH in women with pituitary suppression and to evaluate its possible interference on the reproductive axis. METHODS: a total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction, due to a male or tubal factor, and 20 patients using estradiol valerate, for endometrial preparation in order to be submitted to oocyte donation treatment were studied. All patients used GnRH analogues before starting treatment in order to avoid premature LH surge. Data were analyzed statistically by the chi2 test, Student's t-test and the Pearson correlation test, when appropriate, with the level of significance set at p<0,05. RESULTS: it was observed that leptin levels correlated with body mass index (BMI even though they had not influenced growth rate of these hormones. A positive correlation was observed between estradiol and leptin levels in both

Neonatal androgenization of hypogonadal (hpg male mice does not abolish estradiol-induced FSH production and spermatogenesis

Directory of Open Access Journals (Sweden)

Kerr Jeffrey B

2005-09-01

Full Text Available Abstract Background Testicular development is arrested in the hypogonadal (hpg mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response to estradiol in the male hpg mouse might be due to inadequate masculinisation or incomplete defeminization in the neonatal period. Previous studies have demonstrated that treatment of hpg mice with testosterone propionate in the immediate neonatal period is necessary to allow full reproductive behaviors to be expressed following suitable endocrine stimulation at adult ages. Methods Hpg mice were treated with 100 μg testosterone propionate or vehicle on postnatal day 2. At 35 days of age, subgroups of these mice were treated with silastic implants containing estradiol or cholesterol. Reproductive behavior was scored in tests with steroid-primed female mice, then testicular development was assessed histologically, and measures of pituitary FSH content made at 85 days of age. Results The neonatal testosterone propionate treatment successfully defeminized female litter mates, as revealed by impaired vaginal opening and deficiencies in lordosis behavior, and it allowed appropriate male reproductive behavior to be expressed in a proportion of the hpg males when tested at an adult age. However, neonatal androgen supplementation did not block or even reduce the subsequent actions of estradiol in increasing pituitary FSH content, nor did it affect the ability of estradiol to induce qualitatively normal spermatogenesis. Conclusion The ability of the hpg male to show a "female" neuroendocrine response to estradiol is not a result of inadequate androgenization during neonatal development, and

Ultrastructure of sheep primordial follicles cultured in the presence of indol acetic acid, EGF, and FSH

DEFF Research Database (Denmark)

Andrade, Evelyn Rabelo; Hyttel, Poul; Landim-Alvarenga, Fernanda Da Cruz

2011-01-01

The aim of this study was to investigate the ultrastructural characteristics of primordial follicles after culturing of sheep ovarian cortical slices in the presence of indol acetic acid (IAA), Epidermal Growth Factor (EGF), and FSH. To evaluate ultrastructure of primordial follicles cultured...... in MEM (control) or in MEM containing IAA, EGF, and FSH, fragments of cultured tissue were processes for transmission electron microscopy. Except in the control, primordial follicles cultured in supplemented media for 6¿d were ultrastructurally normal. They had oocyte with intact nucleus...... and the cytoplasm contained heterogeneous-sized lipid droplets and numerous round or elongated mitochondria with intact parallel cristae were observed. Rough endoplasmic reticulum (RER) was rarely found. The granulosa cells cytoplasm contained a great number of mitochondria and abundant RER. In conclusion...

Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment

DEFF Research Database (Denmark)

Andersen, A Nyboe; Witjes, H; Gordon, K

2011-01-01

Prediction of ovarian response prior to the first controlled ovarian stimulation (COS) cycle is useful in determining the optimal starting dose of recombinant FSH (rFSH). However, potentially predictive factors may be subject to inter-cycle variability and many patients are pre-treated with oral ...

The long-term effects of FSH and triiodothyronine administration during the pubertal period on Connexin 43 expression and spermatogenesis efficiency in adult rats.

Science.gov (United States)

Marchlewska, Katarzyna; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Filipiak, Eliza; Kula, Krzysztof

2015-04-01

Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome

Directory of Open Access Journals (Sweden)

Yovich JL

2016-08-01

Full Text Available John L Yovich,1,2,* Birgit Alsbjerg,3,4,* Jason L Conceicao,1 Peter M Hinchliffe,1 Kevin N Keane1,2,* 1PIVET Medical Centre, Perth, 2School of Biomedical Science, Curtin Health Innovation Research Institute Bioscience, Curtin University, Perth, WA, Australia; 3The Fertility Clinic, Skive Regional Hospital, Skive, 4Faculty of Health, Aarhus University, Aarhus, Denmark *These authors contributed equally to this work Abstract: The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Müllerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting ≤15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women <40 years with 24% requiring rFSH dosages <150 IU. Applying both specific algorithms in our clinic meant that the starting dose was not altered for

The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH.

Science.gov (United States)

Sacchi, Sandro; D'Ippolito, Giovanni; Sena, Paola; Marsella, Tiziana; Tagliasacchi, Daniela; Maggi, Elena; Argento, Cindy; Tirelli, Alessandra; Giulini, Simone; La Marca, Antonio

2016-01-01

Anti Müllerian Hormone (AMH) has a negative and inhibitory role in many functions of human granulosa-lutein cells (hGCs) including notoriously the reduction of the aromatase CYP19A1 expression induced by follicle-stimulating hormone (FSH). No data have been provided on the possible role of AMH in modulating the response to luteinizing hormone (LH) (alone or combined with FSH) as well as its effect on other enzymes involved in steroidogenesis including aromatase P450scc. The aim of this study was to investigate the role of AMH as regulator of the basal and stimulated steroids production by hGCs. Primary culture of hGCs were incubated with hormones AMH, LH, and FSH, alone or in combination. The CYP19A1 and P450scc messenger RNA (mRNA) expression, normalized by housekeeping ribosomal protein S7 (RpS7) gene, was evaluated by reverse transcriptase quantitative PCR (RT-qPCR). Each reaction was repeated in triplicate. Negative controls using corresponding amount of vehicle control for each hormone treatment were performed. AMH did not modulate the basal mRNA expression of both aromatase genes at any of the concentrations tested. Meanwhile, the strong mRNA induction of CYP19A1 and P450scc generated by a 24-h gonadotropin treatment (alone and combined) was suppressed by 20 ng/ml AMH added to culture medium. These findings contribute in clarifying the relationship between hormones regulating the early phase of steroidogenesis confirming that AMH is playing a suppressive role on CYP19A1 expression stimulated by gonadotropin in hGCs. Furthermore, a similar inhibitory effect for AMH was observed on P450scc gene expression when activated by gonadotropin treatment.

Human steroidogenesis

DEFF Research Database (Denmark)

Andersen, Claus Y; Ezcurra, Diego

2014-01-01

In the menstrual cycle, the mid-cycle surge of gonadotropins (both luteinising hormone [LH] and follicle-stimulating hormone [FSH]) signals the initiation of the periovulatory interval, during which the follicle augments progesterone production and begins to luteinise, ultimately leading to the r......In the menstrual cycle, the mid-cycle surge of gonadotropins (both luteinising hormone [LH] and follicle-stimulating hormone [FSH]) signals the initiation of the periovulatory interval, during which the follicle augments progesterone production and begins to luteinise, ultimately leading...... reviews current knowledge of the regulation of progesterone in the human ovary during the follicular phase and highlights areas where knowledge remains limited. In this review, we provide in-depth information outlining the regulation and function of gonadotropins in the complicated area of steroidogenesis...

Avaliação dos níveis basais de FSH em pacientes inférteis com endometriose profunda de ovário tratadas cirurgicamente Evaluation of basal FSH serum levels in infertile patients with deep ovarian endometriosis who underwent surgery

Directory of Open Access Journals (Sweden)

Sandra Frankfurt

2009-07-01

Full Text Available OBJETIVO: avaliar a reserva ovariana de pacientes inférteis portadoras de endometriose profunda de ovário, submetidas à cirurgia excisional dos endometriomas, atendidas entre os meses de Fevereiro e Novembro de 2008. MÉTODOS: estudo prospectivo que incluiu 30 pacientes portadoras de endometriose graus III e IV com comprometimento profundo de ovário submetidas à cirurgia excisional dos endometriomas e 30 pacientes portadoras de endometriose graus I e II que foram alocadas como Grupo Controle. A reserva ovariana foi avaliada indiretamente a partir do valor do hormônio folículo estimulante (FSH basal (U/L, entre o terceiro e quinto dias do ciclo, após um período de 12 meses da cirurgia. O índice de massa corpórea (IMC foi calculado conforme a fórmula de Quetelet [peso (kg/estatura (cm²]. Para a comparação das variáveis "idade", "IMC" e "valores de FSH basal" entre os grupos, foi utilizado o teste não paramétrico U de Mann-Whitney. RESULTADOS: não foi encontrada diferença significativa entre os grupos em relação à idade e ao IMC. Em relação ao FSH basal, observou-se que, no grupo das pacientes com endometriose profunda, o valor médio foi de 7,0 U/L, enquanto que, no Grupo Controle, foi de 5,6 U/L (p=0,3, o que demonstra que a diferença no valor médio de FSH encontrado nos dois grupos não foi significativa. CONCLUSÕES: a cirurgia não influenciou de forma deletéria a reserva ovariana das pacientes com endometriose profunda de ovário.PURPOSE: to evaluate the ovarian reserve of infertile patients with severe ovarian endrometriosis, submitted to excisional surgery of endometriomas and attended from February to November, 2008. METHODS: prospective study, including 30 patients with endometriosis grades III and IV, with severe ovarian impairment, submitted to excisional surgery of the endometriomas, and 30 patients with endometriosis grades I and II, allocated as a Control Group. The ovarian reserve was indirectly assessed

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis.

Science.gov (United States)

van Tilborg, Theodora C; Oudshoorn, Simone C; Eijkemans, Marinus J C; Mochtar, Monique H; van Golde, Ron J T; Hoek, Annemieke; Kuchenbecker, Walter K H; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose. In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to normalize ovarian response and optimize live birth rates. However, no robust evidence for the (cost-)effectiveness of this practice exists. Between May 2011 and May 2014 we performed a multicentre prospective cohort study with two embedded RCTs in women scheduled for IVF/ICSI. Based on the AFC, women entered into one of the two RCTs (RCT1: AFC 15) or the cohort (AFC 11-15). The primary outcome was ongoing pregnancy achieved within 18 months after randomization resulting in a live birth (delivery of at least one live foetus after 24 weeks of gestation). Data from the cohort with weight 0.5 were combined with both RCTs in order to conduct a strategy analysis. Potential half-integer numbers were rounded up. Differences in costs and effects between the two treatment strategies were compared by bootstrapping. In both RCTs women were randomized to an individualized (RCT1:450/225 IU, RCT2:100 IU) or standard FSH dose (150 IU). Women in the cohort all received the standard dose (150 IU). Anti-Müllerian hormone (AMH) was measured to assess AMH post-hoc as a biomarker to individualize treatment. For RCT1 dose adjustment was allowed in subsequent cycles based on pre-specified criteria in the standard group only. For RCT2 dose adjustment was allowed in subsequent cycles in both groups. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. We included 1515 women, of whom 483 (31.9%) entered the cohort, 511 (33.7%) RCT1 and 521 (34.4%) RCT2. Live births occurred in 420/747 (56.3%) women

Possible applications of RIA of LH and FSH in diagnosis of Stein-Leventhal syndrome

International Nuclear Information System (INIS)

Zenisek, L.; Talas, M.; Stehlikova, J.; Fingerova, H.; Duskova, M.

1981-01-01

LH determination in the serum significantly assists in diagnosing polycystic ovaries. Values exceeding 22 mIU/ml serum are indicative of a typical picture of polycystic ovaries similar to those found in the Stein-Leventhal syndrome. Lower levels indicate an atypical picture of polycystic ovaries or low-cyst ovary degeneration. FSH level cannot be used for this diagnosis. (author)

Possible applications of RIA of LH and FSH in diagnosis of Stein-Leventhal syndrome

Energy Technology Data Exchange (ETDEWEB)

Zenisek, L.; Talas, M.; Stehlikova, J.; Fingerova, H.; Duskova, M.

1981-01-01

LH determination in the serum significantly assists in diagnosing polycystic ovaries. Values exceeding 22 mIU/ml serum are indicative of a typical picture of polycystic ovaries similar to those found in the Stein-Leventhal syndrome. Lower levels indicate an atypical picture of polycystic ovaries or low-cyst ovary degeneration. FSH level cannot be used for this diagnosis.

Clinical significance of changes of plasma leptin and serum T, E2, FSH, LH, PRL levels in patients with polycystic ovary syndrome (PCOS)

International Nuclear Information System (INIS)

Yang Wen; Wang Ying

2010-01-01

Objective: To explore the clinical significance of changes of plasma leptin and serum T, E 2 , FSH, LH, PRL levels in patients with polycystic ovary syndrome(PCOS). Methods: Plasma leptin (with RIA), serum T, E 2 , FSH, LH, PRL (with ECLIA) levels were detected in 31 patients with polycystic ovary syndrome(PCOS) as well as in 35 controls. Results: The plasma leptin and serum T, LH, PRL levels in the patients with PCOS were significantly higher than those in controls (P 2 , FSH levels were not significantly different from those in controls (P>0.05). Plasma leptin levels were positively correlated with those of serum T, LH, PRL (r=0.5784, 0.5411, 0.6082, P<0.01). Conclusion: Development of PCOS was closely related to the plasma leptin and serum T, LH, PRL levels. (authors)

Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide.

Science.gov (United States)

Veeramachaneni, D N R; Palmer, J S; Amann, R P; Kane, C M; Higuchi, T T; Pau, K-Y F

2006-04-01

We studied sequelae of prenatal plus infantile exposure of male rabbits to vinclozolin, because it is ingested by women and children. Female Dutch-Belted rabbits (7-10/group) were treated daily per orum from gestation day 15 through post-natal week 4 to provide 0, 7.2, or 72 mg vinclozolin/kg dam's body weight/day. Vinclozolin had no effect on maintenance of pregnancy, growth of pups, age at testicular descent or weight of organs. Concentrations of serum LH or testosterone at 6, 12, or 24 weeks of age were unaffected. However, FSH was lower (P vinclozolin groups at all three ages. Following injection of GnRH at 12 or 24 weeks, the increase in FSH was less (P vinclozolin groups, as was testosterone at 12 weeks of age. After full sexual maturity, 2 of 7 low dose rabbits were uninterested in female or male teasers and never achieved erection or ejaculation. Overall, rates of ejaculation failure were: control 0% (0/48), low dose 29% (12/42), and high dose 5% (3/60). Daily sperm production per gram of testis and total number of sperm per ejaculate in both vinclozolin groups were similar (P > 0.1) to controls. However, semen from vinclozolin rabbits contained over two times more (P vinclozolin rabbits than in controls. Lesions included syncytia of spherical spermatids and desquamation of germ cells. Hence, developmental exposure to vinclozolin caused presumably permanent changes in copulatory ability, secretion of FSH, and spermiogenesis.

INTERVENSI FOLICLE STIMULATING HORMONE (FSH DALAM PROSES REMATURASI INDUK IKAN GABUS HARUAN Channa Striata Blkr DIDALAM WADAH BUDIDAYA

Directory of Open Access Journals (Sweden)

Akhmad Ridha Fani

2016-06-01

Full Text Available Snakehead and other fish species in waters of the swamp doing spawning at the beginning or in the middle of the rainy season. Gonadal maturation process so as to return time is limited. Aquaculture development is highly dependent on the availability of seeds that meet the timeliness, quality and quantity. The seeds can be produced continuously if supported by the availability of mature broodstock with good quality eggs. Some research about the role of hormones and or the use of stimulants to the success in support of gonad development and spawning, such as; Siam Jambal fish, Pangasius hypophthalmus (Ernawati 1999, Catfish, Clarias batrachus (Zairin et al. 2001, and catfish, Hemibagrus nemurus (Supriyadi 2005. By because they were with potential memamfaatkan folicle Stimulating Hormone (FSH that serves as the control at the start of the reproductive cycle up to ovulation and spermiasi in fish. The aim of this study was to determine the effect of the injection folicle Stimulating Hormone (FSH in the parent rematurisasi catfish. Results from the start 17007-52327 item, 0,63-1,07mm egg diameter, IGS range of 4, 13 to 8.50%, and ranged from 0.86 2.4% IHS. Based on the results of the study injection folicle Stimulating Hormone (FSH capable mepersingkat rematurasi processing time.

Serum LH and FSH Responses to Synthetic LH-RH in Normal Infants, Children and Patients With Turner's Syndrome

Science.gov (United States)

Suwa, Seizo; And Others

1974-01-01

Effects of luteinizing hormone-releasing hormone (LH-RH) on LH and follicle-stimulating hormone (FSH) release were studied in 26 normal children and six patients (from 1-to 14-years-old) with Turner's syndrome. (Author)

Significance of determination of female sex hormones (E2, LH, FSH), insulin-like growth factor I (IGF-I) and leptin in girls with precocious puberty

International Nuclear Information System (INIS)

Huang Jianrong

2004-01-01

Objective: To investigate the diagnostic value of determination of serum levels of estradiol (E 2 ), luteinizing hormone (LH) and follicle stimulating hormone (FSH), insulin-like growth factor (IGF-I) and leptin in girls with idiopathic central precocious puberty (ICPP). Methods: Serum E 2 , LH, FSH, IGF-I (with chemiluminescence immunoassay) and leptin (with RIA) levels were determined in 35 girls with early development of breast as the sign of precocious puberty, of which, 15 was considered to be of the ICPP group and 20 of simple premature thelarche group (SPT). Criteria of diagnosis for ICPP were: peak LH value>12IU/L and LH/FSH>1 after GnRH stimulating test. Results: Serum E 2 , LH, FSH, IGF-I leptin levels in girls with ICPP were significantly higher than those in the girls with SPT (P 0.2 as the cut-off value for diagnosis of ICPP there would still be a positive rate of 86.6% suggesting that the diagnostic criteria might be set lower. Serum IGF-I levels were positively correlated to those of E 2 (r=0.47, P 2 and IGF-I. Conclusion: Determinations of serum E 2 , LH, FHS, IGF-I and leptin levels were helpful for the early diagnosis of ICPP. (author)

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

Science.gov (United States)

van Tilborg, Theodora C; Torrance, Helen L; Oudshoorn, Simone C; Eijkemans, Marinus J C; Koks, Carolien A M; Verhoeve, Harold R; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, A Petra; Schoot, Benedictus C; Sluijmer, Alexander V; Verhoeff, Arie; Groen, Henk; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M

2017-12-01

Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. This

Comparative Gene Expression Profiling in Human Cumulus Cells according to Ovarian Gonadotropin Treatments

Directory of Open Access Journals (Sweden)

Said Assou

2013-01-01

Full Text Available In in vitro fertilization cycles, both HP-hMG and rFSH gonadotropin treatments are widely used to control human follicle development. The objectives of this study are (i to characterize and compare gene expression profiles in cumulus cells (CCs of periovulatory follicles obtained from patients stimulated with HP-hMG or rFSH in a GnRH antagonist cycle and (ii to examine their relationship with in vitro embryo development, using Human Genome U133 Plus 2.0 microarrays. Genes that were upregulated in HP-hMG-treated CCs are involved in lipid metabolism (GM2A and cell-to-cell interactions (GJA5. Conversely, genes upregulated in rFSH-treated CCs are implicated in cell assembly and organization (COL1A1 and COL3A1. Interestingly, some genes specific to each gonadotropin treatment (NPY1R and GM2A for HP-hMG; GREM1 and OSBPL6 for rFSH were associated with day 3 embryo quality and blastocyst grade at day 5, while others (STC2 and PTX3 were related to in vitro embryo quality in both gonadotropin treatments. These genes may prove valuable as biomarkers of in vitro embryo quality.

Differential Expression of Claudin Family Proteins in Mouse Ovarian Serous Papillary Epithelial Adenoma in Aging FSH Receptor-Deficient Mutants

Directory of Open Access Journals (Sweden)

Jayaprakash Aravindakshan

2006-12-01

Full Text Available Ovarian cancer is a deadly disease with long latency. To understand the consequences of loss of folliclestimulating hormone receptor (FSH-R signaling and to explore why the atrophic and anovulatory ovaries of follitropin receptor knockout (FORKO mice develop different types of ovarian tumors, including serous papillary epithelial adenoma later in life, we used mRNA expression profiling to gain a comprehensive view of misregulated genes. Using real-time quantitative reverse transcription-polymerase chain reaction, protein analysis, and cellular localization, we show, for the first time, in vivo evidence that, in the absence of FSH-R signaling, claudin-3, claudin-4, and claudin-11 are selectively upregulated, whereas claudin-1 decreases in ovarian surface epithelium and tumors in comparison to wild type. In vitro experiments using a mouse ovarian surface epithelial cell line derived from wild-type females reveal direct hormonal influence on claudin proteins. Although recent studies suggest that cell junction proteins are differentially expressed in ovarian tumors in women, the etiology of such changes remains unclear. Our results suggest an altered hormonal environment resulting from FSH-R loss as a cause of early changes in tight junction proteins that predispose the ovary to late-onset tumors that occur with aging. More importantly, this study identifies claudin-11 overexpression in mouse ovarian serous cystadenoma.

Regulation of MMP2 and MMP9 metalloproteinases by FSH and growth factors in bovine granulosa cells

Directory of Open Access Journals (Sweden)

Valerio M. Portela

2009-01-01

Full Text Available Matrix metalloproteinases (MMP are key enzymes involved in tissue remodeling. Within the ovary, they are believed to play a major role in ovulation, and have been linked to follicle atresia. To gain insight into the regulation of MMPs, we measured the effect of hormones and growth factors on MMP2 and MMP9 mRNA levels in non-luteinizing granulosa cells in serum-free culture. FSH and IGF1 both stimulated estradiol secretion and inhibited MMP2 and MMP9 mRNA abundance. In contrast, EGF and FGF2 both inhibited estradiol secretion but had no effect on MMP expression. At physiological doses, none of these hormones altered the proportion of dead cells. Although we cannot link MMP expression with apoptosis, the specific down regulation by the gonadotropic hormones FSH and IGF1 in vitro suggests that excess MMP2 and MMP9 expression is neither required nor desired for follicle development.

The effect of Ramadan fasting on LH, FSH, oestrogen, progesterone and leptin in pregnant women.

Science.gov (United States)

Khoshdel, A; Kheiri, S; Hashemi-Dehkordi, E; Nasiri, J; Shabanian-Borujeni, S; Saedi, E

2014-10-01

Many pregnant Muslim women fast during Ramadan. Leptin has an important role in the reproductive system and hormones. In this study, FSH, LH, oestrogen, progesterone and leptin were measured in the first, second and fourth week of Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change during the study. A significant change in FSH, oestrogen, progesterone and leptin was observed (p Ramadan. Progesterone increased at the end of Ramadan and the second week after. Oestrogen increased significantly during Ramadan and decreased after Ramadan. A decreasing trend was seen in LH during the Ramadan and 2 weeks after (p Ramadan. We found poor weight gain and hypoleptinaemia in pregnant fasted women during the study. Food restriction in pregnant fasted women during Ramadan may induce poor weight gain during pregnancy. These data confirm that Ramadan fasting by pregnant women may have potential risks during pregnancy. We recommend further study to evaluate long-term effects of Ramadan fasting during pregnancy in different countries with different food habits and traditions, to obtain reliable and documented data.

Han Chinese polycystic ovary syndrome risk variants in women of European ancestry: relationship to FSH levels and glucose tolerance.

Science.gov (United States)

Saxena, R; Georgopoulos, N A; Braaten, T J; Bjonnes, A C; Koika, V; Panidis, D; Welt, C K

2015-06-01

associated with insulin (-0.16 ± 0.05, P = 0.0029) and glucose levels (-0.20 ± 0.05, P = 0.0002) 120 min after an oral glucose test. The study was large and contained replication cohorts, but was limited by a small number of controls in the Greek cohort and a small number of cases in the second Boston cohort. The second Boston group was identified using electronic medical record review, but was validated for the cardinal features of PCOS. This study demonstrates a cross-ethnic PCOS risk locus in FSHR in women of European ancestry with PCOS. The variant may influence FSH receptor responsiveness as suggested by the associated change in FSH levels. The relationship between a variant near RAB5B and SUOX and glucose stimulated insulin and glucose levels suggests an influence of one of these genes on glucose tolerance, but the absence of a relationship with PCOS points to potential differences in the international PCOS patient populations. The project was supported by Award Number R01HD065029 from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development, Award Number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, award 1-10-CT-57 from the American Diabetes Association and the Partners Healthcare Center for Personalized Genetics Project Grant. C.K.W. is a consultant for Takeda Pharmaceuticals. NCT00166569. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of four mathematical models for the calculation of radioimmunoassay data of LH, FSH and GH

International Nuclear Information System (INIS)

Geier, T.; Rohde, W.

1981-01-01

Weighted linear logit-log regression, point-to-point logit-log interpolation, smoothing spline approximation and the four-parameter logistic function calculated by non-linear regression have been compared. The data for comparison have been obtained from two different pool-sera for each of the LH-, FSH- and GH-RIA and from the basal serum LH values of two populations of children. The Wilcoxon matched pairs signed rank test was used for comparison: For GH there is no significant difference between all methods, for FSH the weighted linear logit-log regression and spline approximation appeared to be equivalent, but for LH no unequivocal assertion can be made. There is no significant difference between the mathematical models for determination of hormone concentration within one assay run of a population as exemplified for LH. In addition, pool sera data were subjected to an analysis of variance and the comparison of the results revealed that the different models did not lead to different statements about assay performance. The point-to-point logit-log interpolation is proposed as most simple curvilinear approximation for assays which cannot be linearized by logit-log transformation. (author)

An unusual cysteine VL87 affects the antibody fragment conformations without interfering with the disulfide bond formation.

Science.gov (United States)

Attallah, Carolina; Aguilar, María Fernanda; Garay, A Sergio; Herrera, Fernando E; Etcheverrigaray, Marina; Oggero, Marcos; Rodrigues, Daniel E

2017-10-01

The Cys residues are almost perfectly conserved in all antibodies. They contribute significantly to the antibody fragment stability. The relevance of two natural contiguous Cys residues of an anti-recombinant human-follicle stimulation hormone (rhFSH) in a format of single-chain variable fragment (scFv) was studied. This scFv contains 5 Cys residues: V H 22 and V H 92 in the variable heavy chain (V H ) and V L 23, V L 87 and V L 88 in the variable light chain (V L ). The influence of two unusual contiguous Cys at positions V L 87 and V L 88 was studied by considering the wild type fragment and mutant variants: V L -C88S, V L -C87S, V L -C87Y. The analysis was carried out using antigen-binding ability measurement by indirect specific ELISA and a detailed molecular modeling that comprises homology methods, long molecular dynamics simulations and docking. We found that V L -C87 affected the antibody fragment stability without interfering with the disulfide bond formation. The effect of mutating the V L -C87 by a usual residue at this position like Tyr caused distant structural changes at the V H region that confers a higher mobility to the V H -CDR2 and V H -CDR3 loops improving the scFv binding to the antigen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Individualized versus standard FSH dosing in women starting IVF/ICSI : An RCT. Part 2: The predicted hyper responder

NARCIS (Netherlands)

Oudshoorn, Simone C.; Van Tilborg, Theodora C.; Eijkemans, Marinus J. C.; Oosterhuis, G. Jur E.; Friederich, Jaap; van Hooff, Marcel H. A.; van Santbrink, Evert J. P.; Brinkhuis, Egbert A.; Smeenk, Jesper M. J.; Kwee, Janet; de Koning, Corry H.; Groen, Henk; Lambalk, Cornelis B.; Mol, Ben Willem J.; Broekmans, Frank J. M.; Torrance, Helen L.

2017-01-01

STUDY QUESTION: Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? SUMMARY ANSWER: Although in women with a predicted

The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response to a gonadotropin-releasing hormone analogue test in healthy prepubertal girls aged 10 months to 6 years

DEFF Research Database (Denmark)

Vestergaard, Esben T; Schjørring, Mia Elbek; Kamperis, Konstantinos

2017-01-01

and bone age were determined in all participants. Forty-eight healthy normal-weight girls aged 3.5 ± 0.2 years (range: 0.8-5.9 years) were included. Serum concentrations of LH and FSH were measured before and 30 min after the gonadorelin injection. RESULTS: The 30-min LH responses (mean ± 2 s.d.) were 5.......2 ± 4.0 and 2.9 ± 2.5 IU/L and the FSH responses were 23.3 ± 16.2 and 14.5 ± 10.3 IU/L in girls aged 0.8-3.0 years and 3.0-5.9 years respectively. This corresponds to upper cut-off limits for LH of 9.2 IU/L (3 years) and 5.3 IU/L (3-6 years). The stimulated LH/FSH ratio was 0.23 ± 0.19 (range 0.......06-0.43) and did not correlate with age. CONCLUSIONS: We found that LH increases up to 9.2 IU/L during GnRH test in healthy normal-weight girls below 3 years of age and that the stimulated LH/FSH ratio did not exceed 0.43. Our findings have important implications for appropriate diagnosis of central precocious...

A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer

DEFF Research Database (Denmark)

Devroey, Paul; Pellicer, Antonio; Nyboe Andersen, Anders

2012-01-01

MG versus 27% with rFSH for the per-protocol (PP) population and 29% versus 27% for the intention-to-treat (ITT) population. Noninferiority of hphMG compared to rFSH was established. Considering frozen cycles initiated within 1 year, the cumulative live birth rate for a single stimulation cycle was 40...... blastocyst replacement in natural cycles initiated within 1 year of each patient's start of treatment. MAIN OUTCOME MEASURE(S): Ongoing pregnancy (primary end point) and live birth rates, as well as pharmacodynamic parameters. RESULT(S): The ongoing pregnancy rate after a fresh cycle was 30% with hph...

The validity of testicular catch-up growth and serum FSH levels in the long-term postoperative assessment of laparoscopic varicocele correction in adolescents

Directory of Open Access Journals (Sweden)

Aniruddh Deshpande

2011-01-01

Conclusions: Testicular catch-up growth may not be a reliable postoperative assessment criterion by itself. Serum FSH levels may be of value in detecting suboptimal outcomes of varicocele surgery in adolescents.

In vitro fertilisation with recombinant follicle stimulating hormone requires less IU usage compared with highly purified human menopausal gonadotrophin: results from a European retrospective observational chart review

Directory of Open Access Journals (Sweden)

Blackmore Stuart

2010-11-01

Full Text Available Abstract Background Previous studies have reported conflicting results for the comparative doses of recombinant follicle stimulating hormone (rFSH and highly purified human menopausal gonadotrophin (hMG-HP required per cycle of in vitro fertilisation (IVF; the aim of this study was to determine the average total usage of rFSH versus hMG-HP in a 'real-world' setting using routine clinical practice. Methods This retrospective chart review of databases from four European countries investigated gonadotrophin usage, oocyte and embryo yield, and pregnancy outcomes in IVF cycles (± intra-cytoplasmic sperm injection using rFSH or hMG-HP alone. Included patients met the National Institute for Health and Clinical Excellence (NICE guideline criteria for IVF and received either rFSH or hMG-HP. Statistical tests were conducted at 5% significance using Chi-square or t-tests. Results Of 30,630 IVF cycles included in this review, 74% used rFSH and 26% used hMG-HP. A significantly lower drug usage per cycle for rFSH than hMG-HP (2072.53 +/- 76.73 IU vs. 2540.14 +/- 883.08 IU, 22.6% higher for hMG-HP; p Conclusions Based on these results, IVF treatment cycles with rFSH yield statistically more oocytes (and more mature oocytes, using significantly less IU per cycle, versus hMG-HP. The incidence of all OHSS and hospitalisations due to OHSS was significantly higher in the rFSH cycles compared to the hMG-HP cycles. However, the absolute incidence of hospitalisations due to OHSS was similar to that reported previously. These results suggest that the perceived required dosage with rFSH is currently over-estimated, and the higher unit cost of rFSH may be offset by a lower required dosage compared with hMG-HP.

Proteomic and functional profiles of a follicle-stimulating hormone positive human nonfunctional pituitary adenoma.

Science.gov (United States)

Wang, Xiaowei; Guo, Tianyao; Peng, Fang; Long, Ying; Mu, Yun; Yang, Haiyan; Ye, Ningrong; Li, Xuejun; Zhan, Xianquan

2015-06-01

Nonfunctional pituitary adenoma (NFPA) is highly heterogeneous with different hormone-expressed subtypes in NFPA tissues including follicle-stimulating hormone (FSH) positive, luteinizing hormone-positive, FSH/luteinizing hormone-positive, and negative types. To analyze in-depth the variations in the proteomes among different NFPA subtypes for our long-term goal to clarify molecular mechanisms of NFPA and to detect tumor biomarker for personalized medicine practice, a reference map of proteome of a human FSH-expressed NFPA tissue was described here. 2DE and PDQuest image analysis were used to array each protein. MALDI-TOF PMF and human Swiss-Prot databases with MASCOT search were used to identify each protein. A good 2DE pattern with high level of between-gel reproducibility was attained with an average positional deviation 1.98 ± 0.75 mm in the IEF direction and 1.62 ± 0.68 mm in the SDS-PAGE direction. Approximately 1200 protein spots were 2DE-detected and 192 redundant proteins that were contained in 141 protein spots were PMF-identified, representing 107 nonredundant proteins. Those proteins were located in cytoplasm, nucleus, plasma membrane, extracellular space, and so on, and those functioned in transmembrane receptor, ion channel, transcription/translation regulator, transporter, enzyme, phosphatase, kinase, and so on. Several important pathway networks were characterized from those identified proteins with DAVID and Ingenuity Pathway Analysis systems, including gluconeogenesis and glycolysis, mitochondrial dysfunction, oxidative stress, cell-cycle alteration, MAPKsignaling system, immune response, TP53-signaling, VEGF-signaling, and inflammation signaling pathways. Those resulting data contribute to a functional profile of the proteome of a human FSH-positive NFPA tissue, and will serve as a reference for the heterogeneity analysis of NFPA proteomes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simvastatin decreases steroid production in the H295R cell line and decreases steroids and FSH in female rats

DEFF Research Database (Denmark)

Jensen, Anna Guldvang; Hansen, Cecilie Hurup; Weisser, Johan J

2015-01-01

.10-0.13μM for SV and from 0.019-0.055μM for SVA. In rats, SV decreased progestagens in ovaries, brain and plasma, and plasma FSH in the M (72.4% decrease) and H group (76.6% decrease). Because progestagens and gonadotropins are major players in fertility, administration of SV might exert negative effects...

Study on the relationship between serum E2, FSH, LH levels and morphologic changes of uterus and ovary in girls with idiopathic central precocious puberty

International Nuclear Information System (INIS)

Li Jingsong; Du Xueliang; Fu Hongliang; Wu Zhen; Gu Rong; Feng Guoqiang; Wu Jingchuan

2003-01-01

Objective: To explore the characteristics of the girls with idiopathic central precocious puberty (ICPP) through study on the relationship between serum E 2 , FSH, LH levels and morphologic changes of uterus and ovary. Methods: Serum E 2 , FSH and LH levels were measured with ECLIA and morphologic changes of uterus and ovary were studied with B-US in 67 girls with idiopathic central precocious puberty. Results: 1) Among the three types of ovaries (type 1, homogeneous type; type 2, small follicular type; type 3, large follicular type), differences of the serum LH and E 2 values were significant (p 2 levels (p 2 levels were correlated to the maximal follicular diameter but not to the total volume of ovary. It proved that there was close relationship between LH levels and follicular development. It also proved that serum E 2 levels was mainly decided by the development status of the follicles irrespective the total ovary volume. 2) Volume of uterus was correlated to both LH and E 2 levels. Development of uterus was significantly estrogen-dependent. 3) Judgement based upon observations on measurement of serum E 2 , LH, FSH levels and morphologic changes of uterus and ovary would be crucial for establishing the diagnosis of idiopathic central precocious puberty

Use of sperm plasmid DNA lipofection combined with REMI (restriction enzyme-mediated insertion) for production of transgenic chickens expressing eGFP (enhanced green fluorescent protein) or human follicle-stimulating hormone.

Science.gov (United States)

Harel-Markowitz, Eliane; Gurevich, Michael; Shore, Laurence S; Katz, Adi; Stram, Yehuda; Shemesh, Mordechai

2009-05-01

Linearized p-eGFP (plasmid-enhanced green fluorescent protein) or p-hFSH (plasmid human FSH) sequences with the corresponding restriction enzyme were lipofected into sperm genomic DNA. Sperm transfected with p-eGFP were used for artificial insemination in hens, and in 17 out of 19 of the resultant chicks, the exogenous DNA was detected in their lymphocytes as determined by PCR and expressed in tissues as determined by (a) PCR, (b) specific emission of green fluorescence by the eGFP, and (c) Southern blot analysis. A complete homology was found between the Aequorea Victoria eGFP DNA and a 313-bp PCR product of extracted DNA from chick blood cells. Following insemination with sperm lipofected with p-hFSH, transgenic offspring were obtained for two generations as determined by detection of the transgene for human FSH (PCR) and expression of the gene (RT-PCR and quantitative real-time PCR) and the presence of the protein in blood (radioimmunoassay). Data demonstrate that lipofection of plasmid DNA with restriction enzyme is a highly efficient method for the production of transfected sperm to produce transgenic offspring by direct artificial insemination.

Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly

Directory of Open Access Journals (Sweden)

Deepa Bhartiya

2016-01-01

Full Text Available Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes. These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility.

Effect of the human follicle-stimulating hormone-binding inhibitor ...

Indian Academy of Sciences (India)

PRAKASH KUMAR

a fragment of FSHBI, and the native protein have similar activity in vitro and both compounds alter FSH action at the receptor level ... of the rest of the cohort and meiotic arrest of oocytes until ... et al 1989) and preliminary studies performed using the partially .... that human ovarian follicular fluid contains a low molecular-.

In vitro transfer rate of 14C from acetate-1-14C into ovarian steroids in the rat ovary during the estrous cycle and effects of LH and FSH

International Nuclear Information System (INIS)

Kimura, F.; Ishida, S.; Seto, K.; Kawakami, M.

1976-01-01

Fluctuations of ovarian biosynthetic activity and effects of exogenous LH and FSH on it during the estrous cycle were investigated by measuring in vitro transfer rates of 14 C from 14 C-1-acetate into progesterone (P), 20α-hydroxy-pregn-4-en-3-one (20α-OH-P) and estrogen (estradiol and estrone, E) in the ovarian homogenates from rats autopsied at 2 hour intervals. The transfer rate of 14 C from 14 C-1-acetate into P was lowest in the afternoon of estrus and increased from the morning of diestrus 1, making its peaks during the afternoon of diestrus 2 and in the midnight of proestrus. The transfer of 14 C into 20α-OH-P was high on the days of diestrus 2 and proestrus with its peak in the afternoon of the latter day. The maximum transfer of 14 C into E in the afternoon of proestrus and a high rate in the morning of estrus with relatively low one in the midnight were observed. Exogenously injected LH (150 μg) or FSH (150 μg) was eigther stimulatory or inhibitory to the transfer rates of 14 C from 14 C-1-acetate into ovarian steroids. During day time of diestrus 2 and midnight between proestrus and estrus, the transfer of 14 C into P and 20α-OH-P increased by LH, and during day time of proestrus and from the afternoon of estrus to the morning of diestrus 1 decreased. The transfr of 14 C into E increased by LH from the afternoon of diestrus 2 to the morning of proestrus, and decreased during the ofternoon of proestrus and from the afternoon of estrus to the morning of diestrus 2. Administration of FSH was also stimulatory or inhibitory. The 14 C transfer into P and 20α-OH-P increased by FSH from the afternoon of estrus to the morning of proestrus, but in the afternoon of proestrus they decreased. Transfer of 14 C into E increased by FSH significantly on the days of diestrus 2 and proestrus, and slightly on the day of estrus, while it decreased in the afternoon of diestrus 1. (author)

Comparison of the Levels of LH and FSH, TSH, Prolactin, Progesterone and Estradiol Hormones between Iranian Infertile Women with Polycystic Ovary Syndrome and Healthy Women

Directory of Open Access Journals (Sweden)

Amir Hossein Hashemi

2016-12-01

Full Text Available Polycystic ovary syndrome (PCOS with the prevalence of 5 to 7% among Iranian women is a leading cause of infertility and endocrine disorder. Metabolic disorders such as increased levels of LH and FSH hormones in these patients was common and influences health of women with PCOS in long-term. Treatment of female infertility and other complications in many cases need to regulate hormones and receive exogenous hormone, and then the effect of female hormones on the disease is very important. In this study, levels of Luteinizing hormone (LH and Follicle stimulating hormone (FSH and other female hormones among Iranian women with PCOS and infertility and healthy people were measured in this regard and values were compared. The result of this study showed that LH and progesterone hormone levels were significantly different in this syndrome than healthy women.

Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

Science.gov (United States)

Barrio, R; de Luis, D; Alonso, M; Lamas, A; Moreno, J C

1999-02-01

To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. Prospective clinical study. Clinical pediatric department providing tertiary care. Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

The development of radioimmunoassay systems for the human pituitary gland

International Nuclear Information System (INIS)

Simionescu, L.

1983-11-01

The aim of the study was the preparation of 1. Human Growth Hormone (HGH), 2. The glycoprotein hormones: Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) and Thyroid Stimulating Hormone (TSH), 3. The Prolactin. 1. A standardised procedure for the preparation of HGH ''clinical grade'' was developed. This HGH can be applied for the treatment of children diagnosed as hypophyseal dwarfism; the preliminary results are encouraging. The final ethanol-soluble fraction is used also for the prolactin preparation. As shown by exclusion chromatography, the lyophilized HGH ''clinical grade'' contains mainly its monomeric form. The purified HGH obtained by processing of frozen glands is suitable as antigen for the preparation of antisera in rabbits. Large quantities of purified HGH were prepared, used as preparation for radioiodination, and proposed as a national reference preparation for immunoassay. The double antibody HGH-RIA system using author's procedure seems to be adequate for the HGH measurements in biological fluids. 2. Using two chromatographic steps (Sephadex G-150, DEAE-cellulose) followed by a preparative electrophoresis (P-PAGE) purified LH was obtained. The measurement of the β-TSH in the P-PAGE eluates showed concentrations lower than the sensitivity limit of the β-TSH RIA system (5microU/ml). The three chromatographic steps (Sephadex G-150, DEAE-cellulose and Sephadex G-100) allowed to separate the FSH from TSH during the third step, FSH being eluted faster than TSH, as resulted from the RIA measurements of the FSH and of β-TSH: Some overlapping of the concentrations of these hormones was observed only in eluates on the descending arm of the FSH peak. 3. The procedure for the isolation and purification of prolactin was developed according to Hwang's method. The extraction procedure started with the discarded step during the HSH ''clinical grade'' preparation and included three chromatographic steps for purification. However, the final product

Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review

Directory of Open Access Journals (Sweden)

Bernd Th Krause

2009-06-01

Full Text Available Bernd Th Krause1, Ralf Ohlinger2, Annette Haase31Center for Endocrinology and Reproductive Medicine, MVZ Uhlandstr, Berlin, Germany; 2Ernst-Moritz-Arndt-University, Department of Gynecology and Obstetrics, Greifswald, Germany; 3Uhlandstr. 162, 10719 BerlinAbstract: Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a

Ovarian response and pregnancy outcome related to mid-follicular LH levels in women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH stimulation

DEFF Research Database (Denmark)

Humaidan, P; Bungum, L; Bungum, M

2002-01-01

stimulation with recombinant FSH. METHODS: Blood samples were prospectively collected from a total of 207 normal women undergoing assisted reproduction and analysed retrospectively. Based on LH levels on stimulation day 8 patients were divided into four groups: 1.51 IU/l. RESULTS...

The influence of chronic exposure to low frequency pulsating magnetic fields on concentrations of FSH, LH, prolactin, testosterone and estradiol in men with back pain.

Science.gov (United States)

Woldanska-Okonska, Marta; Karasek, Michal; Czernicki, Jan

2004-06-01

There is widespread public concern that electromagnetic fields might be hazardous. However, studies on the biological effects of magnetic fields (MFs) have not always been consistent. Influence of extremely-low frequency MFs used in physiotherapy on endocrine system was rarely examined. Therefore, the aim of the present study was to investigate the concentrations of some pituitary (FSH, LH, prolactin) and sex (testosterone, estradiol) hormones in men with back pain exposed to magnetic fields applied during magnetotherapy or magnetostimulation over the period of three weeks. The study was performed on 20 men aged 28-62 years (mean+/-SEM: 46.4+/-2.0 years) suffering from chronic low back pain who underwent magnetotherapy (10 patients, mean age+/-SEM: 48.4 years, range: 28-62 years) or subjected to magnetostimulation (10 patients, mean age+/-SEM: 44.3 years, range: 34-52 years) for 15 days (daily at 10:00 h, with weekend breaks). Blood samples were collected at 08:00 before magnetic field application, one day and one month following the application. Concentrations of hormones were measured by micromethod of chemiluminescence. Both magnetotherapy and magnetostimulation lowered levels of prolactin. The levels of LH decreased significantly one month after magnetotherapy in comparison with the baseline whereas following magnetostimulation slight but insignificant increase was observed. Estradiol concentrations were significantly lower one day and one month following magnetosimulation in comparison to the baseline and did not change after magnetotherapy. No statistically significant changes were observed in levels of FSH and testosterone after either magnetotherapy or magnetosimulation at any time examined. Magnetic fields applied in physiotherapy exert no or very subtle effect on concentrations of FSH, LH, prolactin, testosterone, and estradiol in men.

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study

NARCIS (Netherlands)

Homburg, R.R.; Hendriks, M.L.; König, T.E.; Anderson, R.A.; Balen, A.H.; Brincat, M.; Child, T.; Davies, M.; D'Hooghe, T.; Martinez, A; Rajkhowa, M.; Rueda-Saenz, R.; Hompes, P.G.A.; Lambalk, C.B.

2012-01-01

BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the

Pituitary gonodal axis in fertile and infertile human males

International Nuclear Information System (INIS)

Hafiez, A.A.; Mahmoud, K.Z.; Abbas, E.Z.; Halawa, F.

1984-01-01

Radioimmunoassays of serum PRL, LH, FSH, testosterone and estradiol were performed in normal fertile subjects and infertile patients. The findings in the fertile group suggest that prolactin in human males has a role in steroidogenesis. Oligospermic and azospermic patients revealed hormonal patterns which were significantly higher than in the fertile group. Hyperprolactinemia was found in most cases of both infertile groups indicating that PRL has a significant role. (author)

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes

DEFF Research Database (Denmark)

Aksglaede, L.; Jensen, Rikke Bodin Beck; Carlsen, E.

2008-01-01

testicular failure due to supernumerary X chromosomes. DESIGN: Cross-sectional study. METHODS: In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive...... basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone...

A comprehensive curated resource for follicle stimulating hormone signaling

Directory of Open Access Journals (Sweden)

Sharma Jyoti

2011-10-01

Full Text Available Abstract Background Follicle stimulating hormone (FSH is an important hormone responsible for growth, maturation and function of the human reproductive system. FSH regulates the synthesis of steroid hormones such as estrogen and progesterone, proliferation and maturation of follicles in the ovary and spermatogenesis in the testes. FSH is a glycoprotein heterodimer that binds and acts through the FSH receptor, a G-protein coupled receptor. Although online pathway repositories provide information about G-protein coupled receptor mediated signal transduction, the signaling events initiated specifically by FSH are not cataloged in any public database in a detailed fashion. Findings We performed comprehensive curation of the published literature to identify the components of FSH signaling pathway and the molecular interactions that occur upon FSH receptor activation. Our effort yielded 64 reactions comprising 35 enzyme-substrate reactions, 11 molecular association events, 11 activation events and 7 protein translocation events that occur in response to FSH receptor activation. We also cataloged 265 genes, which were differentially expressed upon FSH stimulation in normal human reproductive tissues. Conclusions We anticipate that the information provided in this resource will provide better insights into the physiological role of FSH in reproductive biology, its signaling mediators and aid in further research in this area. The curated FSH pathway data is freely available through NetPath (http://www.netpath.org, a pathway resource developed previously by our group.

The effect of dietary protein on reproduction in the mare. IV. Serum progestagen, FSH, LH and melatonin concentrations during the anovulatory, transitional and ovulatory periods in the non-pregnant mare

Directory of Open Access Journals (Sweden)

F.E. Van Niekerk

1997-07-01

Full Text Available The effect of total protein intake and protein quality on the serum concentrations of certain reproductive hormones during the anovulatory, transitional and ovulatory periods were studied in 36 Anglo-Arab mares. High-quality protein stimulated FSH and LH production during the late transitional period. Serum progestagen and melatonin concentrations were unaffected by the quality of protein nutrition during the anovulatory period. Mares receiving high-quality protein exhibited a 10-14-day cyclical pattern of FSH release approximately 4-6 weeks earlier than the mares fed the lower-quality protein diet, and also ovulated 3-4 weeks earlier than the mares on the lower-quality protein diet. Progesterone concentrations during the 1st oestrous cycle after the anovulatory period were unaffected by protein quality in the diet.

Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells.

Science.gov (United States)

Park, Jong-Ju; Seong, Hun-Ki; Kim, Jeong-Soo; Munkhzaya, Byambaragchaa; Kang, Myung-Hwa; Min, Kwan-Sik

2017-06-01

Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn 56 of the α-subunit. Both the rec-eCGs were obtained from CHO-K1 cells. The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. The dose-dependent response was highest when 10 ng of rec-eCGβ/α was used. The deglycosylated eCGβ/αΔ56 mutant did not enhance the agonist-stimulated internalization. We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. Our results suggested that the eLH/CGRs are mostly internalized within 60 min by agonist-stimulation by rec-eCG. We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR.

Effect of developmental low dose PBDE 47 exposure on thyroid hormone status and serum concentrations of FSH and inhibin B in male rats

Energy Technology Data Exchange (ETDEWEB)

Andrade, A.J.M.; Kuriyama, S.N.; Akkoc, Z.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

2004-09-15

Several persistent halogenated organic compounds such as PCBs, dioxins and more recently, polybrominated diphenyl ethers (PBDEs) have been shown to disrupt thyroid hormone homeostasis in experimental animals. Particular concern exists regarding exposure to these compounds during critical periods of development when thyroid hormones orchestrate the growth and differentiation of many organs including the brain and the testis. While the contamination levels of PCBs and other persistent organic pollutants have declined in the past years, increasing levels of PBDEs have been detected in environmental and human samples including human breast milk. PBDEs are produced in large quantities and used worldwide as flame retardants in electrical appliances, carpets and furniture upholstery. Similar to other halogenated environmental organic pollutants, PBDEs seem to present a wide range of toxic effects including reproductive, endocrine, neurobehavioral and hepatic toxicity. Recently, it has been demonstrated that in utero and pubertal exposures to DE-71 (a commercial mixture containing mostly tetra- and penta-bromodiphenyl ethers) significantly reduce thyroxine levels (T4) in rats. The present study has focused on the possible effects of the tetra- BDE congener 2,2'4,4'-tetrabromo diphenyl ether (PBDE 47) on thyroid hormone status and associated changes on FSH and inhibin B levels in the developing male rat. We administered a single dose to gravid dams on gestation day 6 of either 140 {mu}g/kg BW or 700 {mu}g/kg BW PBDE 47. These doses are pertinent to human exposure situation because a study by She et al.3 found a mean level of 33.3 {mu}g PBDE 47 /kg fat in human breast adipose tissue with a range from 7.01 to 196 {mu}g PBDE 47 /kg fat.

Differences in gene expression of granulosa cells from women undergoing controlled ovarian hyperstimulation with either recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin

DEFF Research Database (Denmark)

Grøndahl, Marie Louise; Borup, Rehannah; Lee, Young Bae

2009-01-01

randomized study. SETTING: University-based facilities for clinical services and research. PATIENT(S): Thirty women undergoing treatment with vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). INTERVENTION(S): Patients were randomly allocated to receive recombinant FSH or human (hMG) COH...

Relação entre os níveis séricos do hormônio anti-Mulleriano, inibina B, estradiol e hormônio folículo estimulante no terceiro dia e o status folicular ovariano Relationship of serum anti-Müllerian hormone, inhibin B, estradiol and FSH on day 3 with ovarian follicular status

Directory of Open Access Journals (Sweden)

Juliano Brum Scheffer

2007-04-01

Full Text Available OBJETIVO: examinar a hipótese de que o nível sérico do hormônio anti-Mülleriano (HAM reflete o status folicular ovariano. MÉTODOS: Desenho: estudo prospectivo. Pacientes: foram incluídas 101 candidatas à FIV-TE submetidas à estimulação ovariana controlada com agonista de GnRH e FSH. Depois de atingir a supressão da hipófise e antes da administração de FSH (dia basal, os níveis séricos de HAM, inibina B e FSH foram avaliados. O número de folículos antrais foi determinado pela ultra-sonografia (dia basal (folículo antral precoce; 3-10 mm. RESULTADOS: as médias do nível sérico de HAM, inhibina B, E2, P4 e FSH (dia basal foram 3,4±0,14 ng/mL, 89±4,8 pg/mL, 34±2,7 pg/mL, 0,22±0,23 ng/mL e 6,6±0,1 mUI/mL, respectivamente, e a média do número de folículos antrais precoces foi 17±0,39. O nível sérico do HAM foi negativamente correlacionado com a idade (r= -0,19, pPURPOSE: to examine the hypothesis that serum anti-Müllerian hormone (AMH levels reflect the ovarian follicular status. METHODS: Design: prospective study. Patients: we studied 101 IVF-ET candidates undergoing controlled ovarian hyperstimulation with GnRH agonist and FSH. After the achievement of pituitary suppression and before FSH administration (baseline, serum AMH, inhibin B, and FSH levels were measured. The number of antral follicles was determined by ultrasound at baseline (early antral follicles; 3-10 mm. RESULTS: at baseline, median serum levels of AMH, inhibin B, E2, P4 and FSH were 3.42±0.14 ng/mL, 89±4.8 pg/mL, 34±2.7 pg/mL, 0.22±0.23 ng/mL and 6.6±0.1 mIU/mL, respectively, and the mean number of early antral follicles was 17±0.39. Serum levels of AMH were negatively correlated with age (r=-0.19, p<0.04, and positively correlated with number of antral follicles (r=0.65, p<0.0001, but this did not apply to serum levels of either inhibin B, E2 or FSH. CONCLUSION: the data demonstrate an association between AMH and antral follicular counts

Associação entre depressão na perimenopausa e níveis séricos de estradiol e hormônio folículo-estimulante Association between depression in the perimenopause and serum levels of estradiol (E2 and follicle-stimulating hormone (FSH

Directory of Open Access Journals (Sweden)

Cláudio N Soares

2000-03-01

Full Text Available OBJETIVOS: A perimenopausa é freqüentemente associada ao surgimento de alterações físicas e emocionais. Estudos prévios indicam uma associação entre variações dos hormônios folículo-estimulante (FSH, luteinizante (LH bem como de estrógenos e o surgimento de transtornos do humor, particularmente depressão. Este estudo investigou a correlação entre mudanças nos níveis de estradiol (E2 e FSH e a sintomatologia depressiva em mulheres na perimenopausa. MÉTODOS: Cinqüenta mulheres foram recrutadas nos atendimentos de uma clínica de menopausa e de um serviço psiquiátrico para realização de ensaio clínico com uso de 17 b-estradiol ou placebo. Selecionaram-se mulheres em perimenopausa (idade entre 40 e 55 anos, presença de alterações vasomotoras, irregularidade menstrual nos últimos 6 meses e/ou amenorréia há no máximo 12 meses, níveis de FSH>20 UI/L e com diagnóstico de transtorno depressivo pelo DSM-IV (transtorno depressivo maior, transtorno distímico ou transtorno depressivo sem outra especificação. Dosagens séricas iniciais e finais (semana 12 de FSH e E2, bem como avaliações da sintomatologia depressiva (escores da MADRS foram analisadas e suas correlações investigadas. RESULTADOS: As pacientes apresentaram mudanças (pOBJECTIVES: Previous studies suggest that the perimenopause is a period of increased risk for physical and emotional disturbances. The intense fluctuation in hormone levels during the perimenopause has been associated with the presence of depressive symptoms. The present study investigated the association between levels of estradiol (E2 and follicle-stimulating hormone (FSH and the severity of depressive symptoms of women in the perimenopause. METHODS: Fifty perimenopausal women (age: 40-55 years, all meeting DSM-IV criteria for depressive disorders [major depressive disorder, dysthymia or depressive disorders NOS], with irregular periods and FSH levels > 20 IU/L were selected from a larger

The influence of ovarian hyperstimulation drugs on morphometry and morphology of human oocytes in ICSI program.

Science.gov (United States)

Taheri, Fatemeh; Alemzadeh Mehrizi, Arezoo; Khalili, Mohammad Ali; Halvaei, Iman

2018-04-01

To compare the influences of controlled ovarian hyperstimulation (COH) drugs using recombinant follicular stimulating hormone (rFSH) versus human menopausal gonadotropins (hMG) on morphometry and morphology of MII oocytes in ICSI cycles. In this prospective study, 363 MII oocytes from 50 ICSI cycles with male factor infertility were evaluated. The patients were divided into two groups according to the protocols of COH: I- rFSH and II- hMG. The immature oocytes were excluded from the study. All oocytes were categorized into four morphological groups of normal, and those with single, double, or multiple defects. The inclusive morphometrical criteria were: areas and diameters of oocyte, ooplasm, and zona pellucida (ZP). Also, circumferences of oocyte and ooplasm were assessed. The ZP area and ooplasm diameter for both normal and abnormal oocytes were significantly higher in group I (P: .05; P: .028, respectively) compared to group II (P: .023; P: .003, respectively). In abnormal oocytes, ooplasm diameter was higher in group I compared to group II. Furthermore, ooplasm area for abnormal oocytes was significantly higher in group I compared to group II. There was an increasing trend for number of mature oocytes, in abnormal oocytes, for group I (5.53 ± 3.1) in comparison with group II (4.4 ± 2.97; P = .25). The rate of oocytes with normal morphology was significantly higher in hMG, when compared to rFSH groups. Morphometrical parameters were increased in rFSH group, but the normal morphology of oocytes were significantly enhanced in hMG group. Treatment with proper dosage of ovulation induction drugs may enhance the number of normal sized oocytes. Copyright © 2018. Published by Elsevier B.V.

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

Science.gov (United States)

Sykes, D; Out, H J; Palmer, S J; van Loon, J

2001-12-01

The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.

Follicular development and hormonal levels following highly purified or recombinant follicle-stimulating hormone administration in ovulatory women undergoing ovarian stimulation after pituitary suppression for in vitro fertilization: implications for implantation potential.

Science.gov (United States)

Balasch, J; Fábregues, F; Creus, M; Peñarrubia, J; Vidal, E; Carmona, F; Puerto, B; Vanrell, J A

2000-01-01

The main goal in the present study was to compare follicular development and estradiol levels after ovarian stimulation in pituitary suppressed normally ovulating women undergoing IVF, using highly purified urinary follicle stimulating hormone (FSH) (u-FSH-HP) and recombinant FSH (rec-FSH). A secondary variable in our study was embryo implantation potential, which is closely related to appropriate follicular development and oocyte competence. For the main purpose of this study, 30 IVF patients (group 1) were treated during IVF consecutive cycles, using the same stimulation protocol, with u-FSH-HP in the first treatment study cycle and rec-FSH in the second one. As a control group (group 2) for implantation rates obtained in cycles treated with rec-FSH, 30 additional IVF patients were included who underwent a second IVF attempt again with u-FSH-HP. The total dose of FSH used and ovarian response obtained in terms of estradiol plasma levels and the total number of growing follicles on the day of human chronic gonadotropin (HCG) injection were similar in both treatment cycles in group 1 but better follicular dynamics and oocyte maturity were obtained with rec-FSH. The implantation rate was significantly higher in rec-FSH treated cycles in patients in group 1 than in control women (group 2). rec-FSH is more efficacious than u-FSH-HP when used in the same patient in inducing multiple follicular development in down-regulated cycles as indicated by ovarian performance and oocyte maturity. In addition, rec-FSH yields significantly higher implantation rates than u-FSH-HP when used in patients undergoing their second IVF attempt.

Concentrações de FSH, LH, estradiol, progesterona e histamina no soro, no fluido peritoneal e no fluido folicular de mulheres com e sem endometriose FSH, LH, estradiol, progesterone, and histamine concentrations in serum, peritoneal fluid and follicular fluid of women with and without endometriosis

Directory of Open Access Journals (Sweden)

Andréa Pereira de Lima

2006-11-01

Full Text Available OBJETIVOS: relatos da literatura mostram que não há dados conclusivos sobre a associação entre a endometriose e as concentrações de hormônios envolvidos no controle da reprodução. Este estudo foi realizado para determinar as concentrações de FSH, LH, estradiol (E, progesterona (P e histamina (Hi no soro, no fluido peritoneal e no fluido folicular de mulheres com e sem endometriose. MÉTODOS: a extensão da doença foi estadiada de acordo com a American Fertility Society classification (1997. Para a coleta de soro e de fluido peritoneal foram selecionadas 28 mulheres com endometriose submetidas à laparoscopia diagnóstica (18 mulheres inférteis com endometriose I-II e dez mulheres inférteis com endometriose III-IV. Para o grupo controle, foram selecionadas 21 mulheres férteis submetidas à laparoscopia para esterilização tubárea. O fluido folicular foi obtido de 39 mulheres inférteis submetidas a fertilização in vitro (21 mulheres com endometriose e 18 mulheres sem endometriose. RESULTADOS: as concentrações de FSH e LH no soro, no fluido peritoneal e no fluido folicular não diferiram significativamente entre os grupos. As concentrações de E e P no fluido peritoneal foram significativamente mais baixas em mulheres inférteis com endometriose (E: 154,2±15,3 para estágios I-II e 89,3±9,8 ng/mL para estágios III-IV; P: 11,2±1,5 para estágios I-II e 7,6±0,8 ng/mL para estágios III-IV em comparação com mulheres controle (E: 289,1±30,1; P: 32,8±4,1 ng/mL (Testes de Kruskal-Wallis/Dunn; pPURPOSE: literature reports show that there are no conclusive data about the association between endometriosis and the concentrations of hormones involved in the control of reproduction. Thus, the present study was undertaken to determine FSH, LH, estradiol (E, progesterone (P, and histamine (Hi concentrations in serum, peritoneal fluid and follicular fluid of women with and without endometriosis. METHODS: the extent of the disease

Labelling of human follicle stimulant hormone with 125I, for radioimmunoassay

International Nuclear Information System (INIS)

Pinto, H.; Werner, R.S.; Lerario, A.C.; Toledo e Souza, I.T. de; Wajchenberg, B.L.; Pieroni, R.R.

1976-01-01

An efficient labeling of human Follicle Stimulant Harmone is essential to development of sensitive radioimmunoassays. Iodination by Chloramine T method frequently is subject to severe iodination damage and some preparations are unaccetable for radioimmunoassays. Modifications to the Hunter method, changing incubation time, reaction temperature and reducing Chloramine T amount used in the reaction, were performed in obtaining a more effective labeling. FSH-125 I fraction obtained from Sephadex G-75 column purification presented excellent immunoreactivity and quality control of the steps of the reaction demonstrated a high percentage (90%) of intact Follicle Stimulant Hormone [pt

A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization

DEFF Research Database (Denmark)

Loft, A; Egeberg, Anne Noes; Smitz, J

2012-01-01

Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? SUMMARY ANSWER: Supplementation with hCG from the first day of stimulation may increase the number of top-quality embryos per patient. Daily doses...... has been previously reported. We suggest a large clinical trial to be proceeded with a group given 100 IU hCG daily versus a control group. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prospective multicentre studies have indicated increased live birth rates and increased number of top-quality embryos when...

Reconstitution of hormone-responsive detergent-solubilized follicle stimulating hormone receptors into liposomes

International Nuclear Information System (INIS)

Grasso, P.; Dattatreyamurty, B.; Reichert, L.E. Jr.

1988-01-01

An FSH receptor-enriched fraction that responds to exogenous FSH by activation of adenylate cyclase was prepared by ultrafiltration of sucrose density gradient-purified light membranes derived from bovine calf testes homogenates and solubilized with Triton X-100. To further confirm the functional nature of the detergent-solubilized FSH receptor, the extract was incorporated by lipid hydration into large multilamellar vesicles composed of dioleoyl phosphatidylcholine and cholesterol, 2:1 molar ratio. Receptor incorporation was determined by measurement of specific binding of [125I] human FSH ([125I] hFSH). Substitution of dioleoyl phosphatidylcholine with dipalmitoyl phosphatidylcholine or increasing the cholesterol concentration of the vesicles reduced specific binding of [125I]hFSH. Under conditions favoring optimal incorporation of the receptor, specific binding of [125I]hFSH was time and temperature dependent and saturable when increasing concentrations of radioligand were added to a constant amount of proteoliposomes. Reconstituted proteoliposomes bound 1600 fmol FSH/mg protein with an affinity of 3.54 x 10(9) M-1. Inhibition of [125I] hFSH binding by hFSH was comparable to that seen with the membrane-bound receptor (ED50 = 10 ng). Equilibrium binding studies with [3H]Gpp(NH)p indicated that a single class of high affinity GTP binding sites with an association constant (Ka) of 3.33 x 10(7) m-1 which bound 2.19 fmol [3H]Gpp(NH)p/mg protein had also been incorporated into the proteoliposomes. Addition of FSH induced a 2-fold stimulation of [3H]Gpp(NH)p binding, supporting our earlier studies suggesting that the detergent-solubilized FSH receptor is complexed to the G protein. Of particular significance in the present study was the observation that both NaF and FSH stimulated cAMP production in the reconstituted system

Inhibition of Follicle-Stimulating Hormone-Induced Preovulatory Follicles in Rats Treated with a Nonsteroidal Negative Allosteric Modulator of Follicle-Stimulating Hormone Receptor1

OpenAIRE

Dias, James A.; Campo, Brice; Weaver, Barbara A.; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M.; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M.

2013-01-01

We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human F...

Molecular cloning of a novel, putative G protein-coupled receptor from sea anemones structurally related to members of the FSH, TSH, LH/CG receptor family from mammals

DEFF Research Database (Denmark)

Nothacker, H P; Grimmelikhuijzen, C J

1993-01-01

hormone (FSH, TSH, LH/CG) receptor family from mammals, including a very large, extracellular N terminus (18-25% sequence identity) and a 7 transmembrane region (44-48% sequence identity). As with the mammalian glycoprotein hormone receptor genes, the sea anemone receptor gene yields transcripts which can...... be alternatively spliced, thereby yielding a shortened receptor variant only containing the large extracellular (soluble) N terminus. All this is strong evidence that the putative glycoprotein hormone receptor from sea anemones is evolutionarily related to those from mammals. This is the first report showing...

Inhibin-B secretion and FSH isoform distribution may play an integral part of follicular selection in the natural menstrual cycle

DEFF Research Database (Denmark)

Andersen, C. Yding

2017-01-01

The aim of the present paper is to expand the concept on how follicular selection takes place in the follicular phase of the natural menstrual cycle. It is suggested that inhibin-B exerts a more intimate role in this process than previously understood. Inhibin-B shows a peak in the circulation...... around cycle day 7, simultaneous with selection of the dominant follicle, whereas levels of estradiol and inhibin-A only start to increase a few days later suggesting that inhibin-B is mainly responsible for downregulating pituitary FSH release. New data now demonstrate that the circulatory peak...... of inhibin-B is reflected by peak production of inhibin-B, in contrast to inhibin-A, in the selected follicle with a diameter of 10-12 mm, where concentrations are one thousand times higher than in the circulation. This high inhibin-B concentration also exerts paracrine effects, stimulating theca cell...

Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells

International Nuclear Information System (INIS)

Reinsberg, Jochen; Wegener-Toper, Petra; Ven, Katrin van der; Ven, Hans van der; Klingmueller, Dietrich

2009-01-01

The phthalate ester mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of di-(2-ethylhexyl) phthalate, a high-production-volume chemical used as a plasticizer and solvent in numerous consumer products. MEHP has been demonstrated to be a reproductive toxicant in rodents decreasing estradiol and progesterone production in preovulatory granulosa cells. In the present study, we examined the effect of MEHP on steroid production of human granulosa-lutein (GL) cells. Human GL cells collected from women undergoing in vitro fertilization were cultured in medium containing FSH, hCG and 8-Br-cAMP, respectively, together with various concentrations of MEHP (0-500 μmol L -1 ). After incubation for 48 h estradiol and progesterone were assayed in the spent culture medium. Furthermore, aromatase activity and mRNA levels of GL cells were determined. Basal as well as FSH-, hCG- and 8-Br-cAMP-stimulated estradiol production of GL cells was suppressed by MEHP in a dose-dependent manner (IC 50 = 105 μmol L -1 , 138 μmol L -1 , 49 μmol L -1 and 78 μmol L -1 ). Furthermore aromatase activity and mRNA levels were reduced in GL cells cultured with MEHP. In contrast, MEHP did not alter the production of progesterone up to a concentration of 167 μmol L -1 . The present data indicate that MEHP is a specific inhibitor of estradiol production in human GL cells with a post-cAMP site of action. The inhibition of estradiol production obviously results from a reduction of aromatase activity on the transcript level. As the in vitro effective doses of MEHP are within the range of real environmental exposure levels an inhibitory effect on estrogen production in vivo seems to be possible.

Do Different Stimulation Protocols Effect Oocyte Quality and IVF Outcomes in IVF-ET?

Directory of Open Access Journals (Sweden)

Nafiye Yilmaz

2016-04-01

Full Text Available Aim: This study was planned to compare the effect of different stimulation protocols (hMG and uFSH on oocyte maturation and in vitro fertilization outcomes. Material and Method: Eighty-two patients admitted Ankara University Obstetrics and Gynecology Clinic- IVF Department were included in this retrospective study. All patients used long GnRH agonist protocol. Fifty-nine patients used human menopausal gonadotropin (hMG (Group 1 and 23 patients used urine derived follicle-stimulating hormone (uFSH (Group 2 for ovulation induction. Maximum follicle diameter, dominant follicle number, endometrial thickness at human chorionic gonadotropin day, duration of induction, dose of gonadotropin, oocyte number and quality, fertilization rate, embryo number and quality, pregnancy rate per cycles and transfer were reported. Results: Maximum follicle diameter, dominant follicle number, immature oocyte number were significantly higher in hMG group vs. uFSH group (p0.05. Discussion: Clinical pregnancy rate was not significantly different in hMG vs. uFSH group. In developing countries, ovarian stimulation agents should be chosen based on patient characteristics and cost.

Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty.

Science.gov (United States)

Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise; Sørensen, Kaspar; Petersen, Jorgen Holm; Andersson, Anna-Maria; Juul, Anders

2017-10-01

Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients. Population-based and outpatient clinic. Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Clinical pubertal staging, including serum and urinary gonadotropin levels. Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs. Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty. Copyright © 2017 Endocrine Society

Maturation of human oocytes in vitro

Directory of Open Access Journals (Sweden)

Mojca Čižek-Sajko

2007-01-01

Full Text Available Background: Immature oocyte retrieval followed by in vitro maturation is a promising infertility treatment option. In patients with morphologically normal ovaries and regular menstrual cycles and in patients with polycystic ovary syndrome (PCOS we attempted to assess the success of oocyte in vitro maturation in in vitro fertilization (IVF procedures.Methods: Retrospectively we analyzed 87 IVF procedures with in vitro maturation of oocytes carried out in 73 infertile couples treated at the Maribor Teaching Hospital. We compared the success following three different hormone priming protocols: regular cycling patients with normal ovaries and without hormone priming (Group A, n = 27; patients with PCOS and hormone priming with follitropin (follicle stimulating hormone, FSH (Group B, n = 22; patients with PCOS and hormone priming with human chorionic gonadotrophin (hCG (Group C, n = 38. Success of the procedure was evaluated on the basis of the ability of oocytes to mature, fertilize and develop into embryos, and on the basis of the quality of embryos and their ability to implant in the uterus.Results: In regular cycling patients with normal ovaries (n = 27 we obtained a significantly lower number of immature oocytes (3.2 ± 2.5 compared with patients with PCOS and FSH priming (11.7 ± 7.2 or those with PCOS and hCG priming (10.4 ± 7.2. The oocyte maturation rate, the fertilization rate and the embryo cleavage rate were as follows: in Group A 57.7 %, 63.2 % and 91.7 %, in Group B 57.6 %, 66.2 % and 90.0 %, and in Group C 58.0 %, 66.2 % and 91.0 % (the differences between groups were not statistically significant. Six pregnancies were recorded only in patients with PCOS. The pregnancy rate per embryo transfer was 1/20 (5.0 % in patients with FSH priming, and 5/33 (15.2 % in patients with hCG priming.Conclusions: Oocyte in vitro maturation is successful in patients with normal ovaries and regular menstrual cycle as well as in those with polycystic

Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: distributions of sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

International Nuclear Information System (INIS)

Green, E.D.; Baenziger, J.U.

1988-01-01

The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear α-subunits with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (α2,3 versus α2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity

A review of luteinising hormone and human chorionic gonadotropin when used in assisted reproductive technology

DEFF Research Database (Denmark)

Ezcurra, Diego; Humaidan, Peter

2014-01-01

to the purification process, thus hCG, mimicking LH action, is added to standardise the product. However, unlike LH, hCG plays a very minor role during the natural human menstrual cycle. It is secreted by the embryo and placenta, and its main role is to support implantation and pregnancy. More recently, recombinant......Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture...... of the hormones, follicle-stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG), but also other biologically active contaminants, such as growth factors, binding proteins and prions. The actual amount of molecular LH in hMG preparations varies considerably due...

Gonadotropin binding sites in human ovarian follicles and corpora lutea during the menstrual cycle

Energy Technology Data Exchange (ETDEWEB)

Shima, K.; Kitayama, S.; Nakano, R.

1987-05-01

Gonadotropin binding sites were localized by autoradiography after incubation of human ovarian sections with /sup 125/I-labeled gonadotropins. The binding sites for /sup 125/I-labeled human follicle-stimulating hormone (/sup 125/I-hFSH) were identified in the granulosa cells and in the newly formed corpora lutea. The /sup 125/I-labeled human luteinizing hormone (/sup 125/I-hLH) binding to the thecal cells increased during follicular maturation, and a dramatic increase was preferentially observed in the granulosa cells of the large preovulatory follicle. In the corpora lutea, the binding of /sup 125/I-hLH increased from the early luteal phase and decreased toward the late luteal phase. The changes in 3 beta-hydroxysteroid dehydrogenase activity in the corpora lutea corresponded to the /sup 125/I-hLH binding. Thus, the changes in gonadotropin binding sites in the follicles and corpora lutea during the menstrual cycle may help in some important way to regulate human ovarian function.

Hormone patterns in early human gestation

International Nuclear Information System (INIS)

Mishell, D.R. Jr.; Thorneycroft, I.H.; Nagata, Y.; Murata, T.; Nakamura, R.M.

1974-01-01

Accurate measurement of the low concentration of gonadotropins and steroid hormones present in human serum has been made possible by the development of sensitive radioimmunoassay (RIA) techniques. With the use of RIA FSH and LH, progesterone and 17OH-progesterone have been previously measured in early normal pregnancy. In order to determine the daily pattern of hormone levels in early normal pregnancy, gonadotropins as well as steroid hormone levels were measured in serum samples obtained daily from three women from the time of the last menstrual period prior to conception throughout the first few months of gestation. To further identify the steroid hormone pattern in early normal pregnancy, concentrations of estradiol, progesterone, and 17OH-progesterone were measured in individual serum samples obtained from a group of 158 women with apparently normal gestations who subsequently had therapeutic abortions. (auth)

CINRG: Systems Biology of Glucocoricoids in Muscle Disease

Science.gov (United States)

2014-12-01

amyotrophic lateral sclerosis; BMD, Becker muscular dystrophy ; COX, cytochrome c oxidase; DMD, Duchenne mus- cular dystrophy ; FSH...to a lesser extent, in Becker muscular dystrophy (BMD; dystrophin mutation), LGMD2A (limb girdle muscular dystrophy type 2A; CALP3 [calpain 3...muscular dystrophy (FSH), normal human skeletal muscle (NHM), amyotrophic lateral sclerosis (ALS), acute quadriplegic myopathy (AQM), Becker muscular

Stimulatory effect of clebopride on human prolactin secretion.

Science.gov (United States)

Perez-Lopez, F R; Legido, A; Sisskin, M; Abos, M D

1980-11-01

Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P clebopride, the PRL response was completely abolished as compared with the control experiment (P clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

Immunohistochemical distribution of regulatory peptides in the human fetal adenohypophysis

Science.gov (United States)

Reyes, R; Valladares, F; Gutiérrez, R; González, M; Bello, A R

2008-01-01

We have studied here the cellular distribution of several regulatory peptides in hormone-producing cells of the human pituitary during the fetal period. Immunohistochemistry was used to show the expression of several regulatory peptides, namely Angiotensin-II, Neurotensin and Galanin, at successive gestational stages and their co-localization with hormones in the human fetal adenohypophysis. Somatotrophs, gonadotrophs and thyrotrophs were differentiated earliest. At gestational week 9, Angiotensin-II immunoreactivity was co-localized only with growth hormone immunoreactivity in somatotrophs, one of the first hormone-producing cells to differentiate. This co-localization remained until week 37. Neurotensin immunoreactivity was present in gonadotrophs and thyrotrophs in week 23, after FSH and TSH hormone differentiation. Galanin immunoreactivity was present in all hormone-producing cell types except corticotrophs. The different pro-opiomelanocortin-derived peptides were detected at different stages of gestation and adrenocorticotrophic hormone immunoreaction was the last to be detected. Our results show an interesting relationship between regulatory peptides and hormones during human fetal development, which could imply that these peptides play a regulatory role in the development of pituitary function. PMID:18510508

Testicular growth and development in puberty.

Science.gov (United States)

Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

2017-06-01

To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

Directory of Open Access Journals (Sweden)

Varras Michail

2012-11-01

Full Text Available Abstract Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21. The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum. No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47

Sex, kings and serial killers and other group-selected human traits.

Science.gov (United States)

Bowles, J T

2000-06-01

(Note: This unorthodox paper contains the first argument for heart disease being a programmed age change and promoted by the dramatic, post age-40 increases in the hormones FSH and hCG seen in some individuals.) A recent issue of Science suggests that the evolutionary purpose of sex is unknown. Surviving to adulthood implies a valuable gene combination which is destroyed by sexual recombination. This should be detrimental to offspring. PROPOSED: Sex is group-selected in prey to allow coalescence of beneficial, and disposal of detrimental, mutations in single individuals enabling rapid adaptation to novel predation. Group selection is a universal force driven by local inter-species (not intra-species) competition. Aging, metabolism, litter size, and fixed body size are directly linked. Sexual recombination and chromosomes destroy gene linkage and exist because mutations are usually detrimental, rarely positive, and occur in linked groups. In unevolving environments, sex is selected against and asexuality emerges. Periodic evolution of novel predators, like man, can explain the 'punctuated equilibria' fossil record. Genes inhibited by methylation or chromatin condensation, expressed at older ages in predation-minimized environments, allow for group selection. Stress increases mutation rates and beneficial mutation likelihood. Females select bigger, brighter, louder, or stronger males that can survive predator attention. Size approximates age and thus predator encounters; male traits represent predation-survival potential. Human male traits include, balding, acne, beard-length, wrinkling, graying, nose/ear growth. Progeria accelerates development of most male traits. Domination of groups by single males allows rapid predation-defense evolution: adolescent males are expelled, brave the wild, and expel another group's male to mate. If expelled and dominant males are culled by predation, males reaching puberty first will reproduce. Hormonal acceleration of puberty

The effectiveness of zinc supplementation in men with isolated hypogonadotropic hypogonadism

Directory of Open Access Journals (Sweden)

Yan-Ling Liu

2017-01-01

Full Text Available A multicenter, open-label, randomized, controlled superiority trial with 18 months of follow-up was conducted to investigate whether oral zinc supplementation could further promote spermatogenesis in males with isolated hypogonadotropic hypogonadism (IHH receiving sequential purified urinary follicular-stimulating hormone/human chorionic gonadotropin (uFSH/hCG replacement. Sixty-seven Chinese male IHH patients were recruited from the Departments of Endocrinology in eight tertiary hospitals and randomly allocated into the sequential uFSH/hCG group (Group A, n = 34 or the sequential uFSH plus zinc supplementation group (Group B, n = 33. In Group A, patients received sequential uFSH (75 U, three times a week every other 3 months and hCG (2000 U, twice a week treatments. In Group B, patients received oral zinc supplementation (40 mg day−1 in addition to the sequential uFSH/hCG treatment given to patients in Group A. The primary outcome was the proportion of patients with a sperm concentration ≥1.0 × 106 ml−1 during the 18 months. The comparison of efficacy between Groups A and B was analyzed. Nineteen of 34 (55.9% patients receiving sequential uFSH/hCG and 20 of 33 (60.6% patients receiving sequential uFSH/hCG plus zinc supplementation achieved sperm concentrations ≥1.0 × 106 ml−1 by intention to treat analyses. No differences between Group A and Group B were observed as far as the efficacy of inducing spermatogenesis (P = 0.69. We concluded that the sequential uFSH/hCG plus zinc supplementation regimen had a similar efficacy to the sequential uFSH/hCG treatment alone. The additional improvement of 40 mg day−1 oral zinc supplementation on spermatogenesis and masculinization in male IHH patients is very subtle.

Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

International Nuclear Information System (INIS)

Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.; Stuzman, R.E.

1982-01-01

Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadal function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men

Plurihormonal cells of normal anterior pituitary: Facts and conclusions.

Science.gov (United States)

Mitrofanova, Lubov B; Konovalov, Petr V; Krylova, Julia S; Polyakova, Victoria O; Kvetnoy, Igor M

2017-04-25

plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment.

Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

DEFF Research Database (Denmark)

Rose, Trine Høyer; Röshammar, Daniel; Erichsen, Lars

2016-01-01

reproductive technologies. Methods: Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed...... volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F. Conclusions: The single-dose pharmacokinetics of FE 999049 were adequately described by a population...

Some biological properties of human chorionic follicle stimulating hormone

International Nuclear Information System (INIS)

Tojo, Shimpei; Ashitaka, Yoshihiko; Maruo, Takeshi; Nishimoto, Hiroyuki

1975-01-01

The biological properties of human chorionic FSH (hCFSH) for rat ovaries were investigated. Highly purified hCFSH had similar response to the ovarian augmentation test as bovine FSH and significantly enhanced 3 H-thymidine uptake by granulosa cells and theca cells in the ovary of hypophysectomized rat. In contrast, highly purified hCG little responded to the ovarian augmentation test and had no effect on 3 H-thymidine uptake by the ovary. These results indicate that hCFSH may promote the follicular growth of ovary resulting from granulosa cell proliferation and its enlargement. In addition, freshly harvested porcine granulosa cells were employed in an in vitro system to investigate specific binding of hCFSH to ovarian receptor. Radioiodinated hCFSH ( 125 I-hCFSH) and hCG ( 125 I-hCG) were respectively incubated with cell suspensions. Binding of these hormone preparations was proportional to the cell number and increased with the time of incubation through 120 minutes. The binding ability of 125 I-hCFSH to the cells was greater than that of 125 I-hCG. Increasing concentrations of unlabeled hCFSH in the incubation mixture progressively inhibited the uptake of 125 I-hCFSH by granulosa cells. Unlabeled hCG was not able to compete with 125 I-hCFSH binding. The similar phenomenon to inhibit the binding of 125 I-hCG to the cells was also recognized in the presence of unlabeled hCG. These findings suggest that granulosa cell has at least two different types of receptor sites: one for hCFSH and the other for hCG. (auth.)

Development of a radioimmunoassay for circulating levels of gonadotropin releasing hormone

International Nuclear Information System (INIS)

Moodbidri, S.B.; Joshi, L.R.; Sheth, A.R.; Rao, S.S.

1976-01-01

A specific and sensitive radioimmunoassay system has been developed for measuring gonadotropin releasing hormone (GnRH) in unextracted human serum. Circulating levels of GnRH, LH and FSH were determined in 37 serum samples obtained from twenty normal healthy women on different days of the menstrual cycle. GnRH and LH but not FSH exhibited similar patterns during the menstrual cycle. 125 I-labelled GnRH was used in the RIA system. (author)

EFFECT OF dbcAMP ON PROLIFERATION AND APOPTOSIS OF PORCINE GRANULOSA CELLS in vitro

Directory of Open Access Journals (Sweden)

Richard Alexa

2013-02-01

Full Text Available Cyclic nucleotide cAMP and its target protein kinase A (PKA dependent intracellular mechanisms can play an important role in regulation of ovarian cell function and in mediating gonadotropin action on these cells. The aim of the present study was to examine the effect of cAMP analogue, dibutyryl cyclic adenosine monophosphate (dbcAMP (0; 0.1; 1 and 10 µg/ml or FSH (0; 0,01; 1 IU/ml on proliferation and apoptosis of porcine granulosa cells in vitro. Indices of cell apoptosis (expression of apoptotic peptide bax and proliferation (expression of proliferation-associated peptide PCNA within ovarian granulosa cells were analysed by immunocytochemistry. It was observed that accumulation of PCNA was increased by dbcAMP and FSH at all doses added. The occurrence of bax was also stimulated by dbcAMP after exposition (at 0,1 and 1 µg/ml, but not at dose 10 µg/ml and by FSH (at all doses added. The stimulatory effect of both dbcAMP and FSH on both ovarian cell apoptosis and proliferation suggest, that these substances may promote ovarian follicular cell turnover. The similarity of dbcAMP and FSH effect may indicate that FSH can affect ovarian functions via cAMP-dependent intracellular mechanisms. The present data may provide new tools to regulate human and animal reproductive processes via cAMP-dependent mechanisms.

Dynamic GnRH and hCG testing

DEFF Research Database (Denmark)

Bang, A. Kirstine; Nordkap, Loa; Almstrup, Kristian

2017-01-01

OBJECTIVE: Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) stimulation tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone after Gn...... influence of the tests was illustrated by results from 45 patients suspected of disordered hypothalamic-pituitary-gonadal axis. METHODS: Baseline, stimulated, relative and absolute changes in serum FSH and LH were determined by ultrasensitive TRIFMA, and testosterone was determined by LC-MS/MS. RESULTS......: For the reference group, LH and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4 to 58.8 U/L and 0.2 to 11.8 U/L and FSH decreased in nine men. Testosterone increased approximately 110% (range: 18.7-67.6 nmol/L) during hCG testing. None of the polymorphisms had any major...

Comparison of the effects of pretreatment with Veramix sponge (medroxyprogesterone acetate) or CIDR (natural progesterone) in combination with an injection of estradiol-17β on ovarian activity, endocrine profiles, and embryo yields in cyclic ewes superovulated in the multiple-dose Folltropin-V (porcine FSH) regimen.

Science.gov (United States)

Bartlewski, Pawel M; Seaton, Patricia; Szpila, Patrycja; Oliveira, Maria E F; Murawski, Maciej; Schwarz, Tomasz; Kridli, Rami T; Zieba, Dorota A

2015-10-15

Follicular wave status at the beginning of exogenous FSH administration is an important contributor to variability in superovulatory responses in ruminants. Studies in ewes have shown a decrease in the number of ovulations when superovulation is initiated in the presence of ostensibly ovulatory-sized ovarian follicles. Hormonal ablation of large antral follicles with the progestin-estradiol (E2-17β) treatment significantly reduces this variability in superovulated anestrous ewes, but the effects of the treatment in cycling ewes have not yet been assessed. Sixteen Rideau Arcott × Polled Dorset ewes (November-December) received either medroxyprogesterone acetate (MAP)-releasing intravaginal sponges (60 mg) or controlled internal drug release (CIDR) devices (containing 300 mg of natural progesterone) for 14 days (Days 0-14), with a single intramuscular injection of 350 μg of E2-17β on Day 6. The superovulatory treatment consisted of six injections of porcine FSH (Folltropin-V) given twice daily, followed by a bolus GnRH injection (50 μg intramuscular) on Day 15. There were no differences (P ewes. In both subsets of animals, the next follicular wave emerged ∼2.5 days after an E2-17β injection (P > 0.05). A decline in maximum follicle size after an E2-17β injection was more abrupt in CIDR- compared with MAP-treated animals, and the ewes pretreated with exogenous progesterone had significantly more 3-mm follicles at the start of the superovulatory treatment. The metabolic clearance rate of exogenous E2-17β appeared to be greater in MAP-treated ewes, but circulating concentrations of porcine FSH failed to increase significantly after each Folltropin-V injection in CIDR-treated animals. The CIDR-treated ewes exceeded (P ewes receiving E2-17β before ovarian superstimulation, there were no differences in superovulatory responses. Copyright © 2015 Elsevier Inc. All rights reserved.

GnRH-agonist implantation of prepubertal male cats affects their reproductive performance and testicular LH receptor and FSH receptor expression.

Science.gov (United States)

Mehl, N S; Khalid, M; Srisuwatanasagul, S; Swangchan-Uthai, T; Sirivaidyapong, S

2016-03-15

This study was conducted to investigate the effect of GnRH-agonist implantation in prepubertal tomcats on sexual behavior, reproductive performance, and expression of testicular LH receptor (LHR) and FSH receptor (FSHR) and also to compare the testicular characteristics, LHR and FSHR expression between prepubertal and adult tomcats. In experiment 1, 3-month-old tomcats (n = 6/group) were either treated with or left without 4.7 mg deslorelin implants. Semen collection and evaluation were performed just before castration at 48 weeks after treatment; removed testes were analyzed for mRNA and protein expression of LHR and FSHR. We were able to collect semen from six non-treated cats, whereas in treated cats, semen was uncollectable. The results revealed that sexual behavior was absent in the implanted cats throughout the study period. Testicular volume was found to decrease from 30 weeks after treatment onward in the implanted cats compared to the controls (P score, seminiferous tubule diameter, and LHR protein expression were found lower in the implanted cats (P reproductive function without any adverse effects for at least 48 weeks in male cats. Copyright © 2016 Elsevier Inc. All rights reserved.

AMH and AMHR2 polymorphisms and AMH serum level can predict assisted reproduction outcomes: a cross-sectional study.

Science.gov (United States)

Peluso, Carla; Fonseca, Fernando L A; Gastaldo, Guilherme G; Christofolini, Denise M; Cordts, Emerson Barchi; Barbosa, Caio P; Bianco, Bianca

2015-01-01

In human assisted reproduction, the ovarian response to exogenous recombinant Follicle-stimulating Hormone (FSH) therapy is variable and difficult to predict. The standard protocol of ovarian hyperstimulation can result in satisfactory response; however, an unsatisfactory response necessitates FSH dose adjustment or results in ovarian hyperstimulation syndrome (OHSS). Polymorphisms in AMH and AMHR2 genes appear to affect hormone biological activities, thus affecting follicle recruitment and development, leading to infertility. We aimed to evaluate AMH and AMHR2 polymorphisms in infertile women, and correlate those findings with AMH, FSH and estradiol serum level response to controlled ovarian hyperstimulation (COH), as well as assisted reproduction outcomes. A cross-sectional study comprising 186 infertile women that underwent one cycle of high complexity assisted reproductive treatment. Blood samples were collected and a TaqMan assay was used for AMH G146T/rs10407022 and AMHR2 A-482G/rs2002555, A10G/rs11170555, C1749G/rs2071558 and G4952A/rs3741664 genotyping, and FSH, estradiol and AMH levels were measured. The findings were correlated to human reproduction outcomes. AMH rs10407022 and AMHR2 rs2002555 polymorphisms were not associated with hormonal measurements, whereas AMHR2 rs11170555 and rs3741664 were positively associated with AMH, estradiol and FSH levels. The genotype distribution of AMH and AMHR2 genes according to Controlled Ovarian Hyperstimulation did not show a positive association. However, an association with AFC, degree of oocyte maturation (allele G of AMHR2 rs2071558) the number of embryos produced (alleles T and G of AMH rs10407022 and AMHR2 rs2002555, respectively) and frozen embryo (allele G of AMHR2 rs11170555) were found to be statistically associated. Considering COH, serum AMH and AFC were a positive predictor to OHSS. Regarding serum AMH and assisted reproduction outcomes, a positive correlation with all variables studied was found

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

Science.gov (United States)

Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. Materials and methods We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. Results We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Conclusion Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment. PMID:28418929

Treatment preferences and outcome in male hypogonadotropic hypogonadism: an Indian perspective.

Science.gov (United States)

Sanyal, D; Chatterjee, S

2016-06-01

This retrospective study assessed treatment preferences and outcome with testosterone or HCG / HCG-FSH combination in Indian male idiopathic hypogonadotropic hypogonadism (IHH) subjects (n = 31) above 18 years of age. 38.7% of IHH study subjects had no fertility plans and chose 3 monthly intramuscular testosterone undecanoate. 73.7% of subjects with fertility plans chose human chorionic gonadotropin (HCG) alone due to cost considerations. Spermatogenesis occurred in 21.4% on HCG alone and 60% of subjects on HCG with follicle-stimulating hormone (FSH) combination. Treatment failure is higher than published Western rates. FSH and HCG combination regimen is costly but superior to HCG alone. However, treatment failure still persists, suggesting unknown testicular defect in IHH. © 2015 Blackwell Verlag GmbH.

Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

Science.gov (United States)

Wechowski, Jaroslaw; Connolly, Mark; Schneider, Dirk; McEwan, Philip; Kennedy, Richard

2009-04-01

To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. Fifty-three fertility clinics in 13 European countries and Israel. Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

Critical evaluation of the radioiodination of follicle-stimulating-and luteinizing hormones by lactoperoxidase and its comparison with chloramine-T classical method

International Nuclear Information System (INIS)

Pinto, H.

1978-01-01

A method is described for the enzymatic radioiodination of human gonadotropins by a system consisting of lactoperoxidase, hydrogen peroxide and Na 125 I. A comparison witth the clhloramine-T modified technique was done a satisfactory specific activity (100 μCi/μg) of the labeled hormone was obtained with the enzymatic iodination, with much greater immunoreactivity and stability than after chloramine-T. As aqueous polyethylene glycol causes precipitation of antibody-bound peptide hormones with radioactive iodine with little or no precipitation of free hormones, a method of separation was developed and applied to radioimmunoassay of gonadotropins, providing several advantages over te double-antibody precipitation method. It was demonstrated that, in humans, the intravenous administration of synthetic LH-FSH/RH, stimulates the pituitary release of both LH and FSH. Results are reported now for normal women, infused with an acute load of 25μg of synthetic LH/FSH-RH and 8 hours infusion of 100μg, during the mid-follicular and luteal phases. The greatest gonadotropin responsiveness to LH/FSH-RH are found in the luteal phase during acute testing. No differences were noticed during chronic infusion as well as acute post-chronic, performed in both phases of the menstrual cycle. The possible modulating effects of steroidal secretion by the ovaries are discussed. (Author) [pt

Analysis of recombinant and native human lutropin/luteotrophin and human chorionic gonadotropin by reversed-phase high performance liquid chromatography

International Nuclear Information System (INIS)

Almeida, Beatriz Elane de

2009-01-01

Specific RP-HPLC conditions for the analysis of recombinant and native hLH and hCG preparations and of their subunits were set up. Heterodimeric hLH and hCG and their alpha and beta subunits all migrated with significantly different retention times (t R ) in the following order of increasing hydrophobicity: alpha-hCG R = 38.35 +- 0.42 min; RSD = 1.1 %; n = 4 preparations), while the hCG main peak ran about 4 % faster when compared to this average value. Human LH, hFSH and hCG peaks could also be identified in the heterogeneous urinary preparations. Quantitative analysis could be validated for the seven homogeneous preparations and accuracy, precision and sensitivity were calculated on the basis of a highly linear dose-response curve (r=0.99998; p<0.0001; n=20). Quantification of the different gonadotropins in the heterogeneous urinary preparations was also carried out, though with clear accuracy limitations. (author)

Human reproduction functions: Evaluation with radiobioassay

International Nuclear Information System (INIS)

El Hassan, N.D.

1983-01-01

Many studies reveal that the ovary is capable of responding to an adequate gonadotropic stimulus long before menarche. Similarly, the pituitary is capable of producing gonadotropins in response to an adequate hypothalamic signal before menarche. Recent studies in the primate confirm that the hypothalamus signals are temporarily different before menarche as compared to the reproductive years, so that if the luteotropic hormone (LRH) stimulus is pulsed to the pituitary at the required time sequence, the follicle stimulating hormone (FSH) and the luteinizing hormone (LH) as well as ovulation can be achieved even in the immature monkey. HPL is another hormone produced by the syncytiotrophoblast that is also used to identify pregnancies at a higher risk of fetal demise. It shares structural similarities with the human growth hormone (hGH) and PRL. HPL is diabetogenic. Its effect is mediated through glucose metabolism. Circulating HPL is elevated during multiple gestations. Its circulating levels in fact correlate with the fetoplacental mass. It has a short half-life and the larger the fetoplacental mass, the higher the HPL level. Hyperglycemic states are associated with a decrease in HPL levels, and hypoglycemia is associated with elevated levels of HPL. RIA through the measurement of HPL has helped in the management of the high-risk fetus and its mother. Through RIA other fetoplacental hormones are identifiable and their levels are obtainable. There is a human chorionic ACTH, a human chorionic TSH, and a human chorionic PRL. These can be involved in health and disease

Use of letrozole in assisted reproduction: a systematic review and meta-analysis

Science.gov (United States)

Requena, Antonio; Herrero, Julio; Landeras, José; Navarro, Esperanza; Neyro, José L.; Salvador, Cristina; Tur, Rosa; Callejo, Justo; Checa, Miguel A.; Farré, Magí; Espinós, Juan J.; Fábregues, Francesc; Graña-Barcia, María

2008-01-01

BACKGROUND Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. METHODS A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66–2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73–2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70–2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78−1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67–2.91). CONCLUSIONS Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction. PMID:18812422

Molecular cloning and characterization of pirarucu (Arapaima gigas follicle-stimulating hormone and luteinizing hormone β-subunit cDNAs.

Directory of Open Access Journals (Sweden)

Thais Sevilhano

Full Text Available The common gonadotrophic hormone α-subunit (GTHα has been previously isolated by our research group from A. gigas pituitaries; in the present work the cDNA sequences encoding FSHβ and LHβ subunits have also been isolated from the same species of fish. The FSH β-subunit consists of 126 amino acids with a putative 18 amino acid signal peptide and a 108 amino acid mature peptide, while the LH β-subunit consists of 141 amino acids with a putative 24 amino acid amino acid signal peptide and a 117 amino acid mature peptide. The highest identity, based on the amino acid sequences, was found with the order of Anguilliformes (61% for FSHβ and of Cypriniformes (76% for LHβ, followed by Siluriformes, 53% for FSHβ and 75% for LHβ. Interestingly, the identity with the corresponding human amino acid sequences was still remarkable: 45.1% for FSHβ and 51.4% for LHβ. Three dimensional models of ag-FSH and ag-LH, generated by using the crystal structures of h-FSH and h-LH as the respective templates and carried out via comparative modeling and molecular dynamics simulations, suggested the presence of the so-called "seat-belt", favored by a disulfide bond formed between the 3rd and 12th cysteine in both β-subunits. The sequences found will be used for the biotechnological synthesis of A. gigas gonadotrophic hormones (ag-FSH and ag-LH. In a first approach, to ascertain that the cloned transcripts allow the expression of the heterodimeric hormones, ag-FSH has been synthesized in human embryonic kidney 293 (HEK293 cells, preliminarily purified and characterized.

Molecular cloning and characterization of pirarucu (Arapaima gigas) follicle-stimulating hormone and luteinizing hormone β-subunit cDNAs.

Science.gov (United States)

Sevilhano, Thais; Carvalho, Roberto Feitosa de; Oliveira, Nélio Alessandro de Jesus; Oliveira, João Ezequiel; Maltarollo, Vinicius Gonçalves; Trossini, Gustavo; Garcez, Riviane; Bartolini, Paolo

2017-01-01

The common gonadotrophic hormone α-subunit (GTHα) has been previously isolated by our research group from A. gigas pituitaries; in the present work the cDNA sequences encoding FSHβ and LHβ subunits have also been isolated from the same species of fish. The FSH β-subunit consists of 126 amino acids with a putative 18 amino acid signal peptide and a 108 amino acid mature peptide, while the LH β-subunit consists of 141 amino acids with a putative 24 amino acid amino acid signal peptide and a 117 amino acid mature peptide. The highest identity, based on the amino acid sequences, was found with the order of Anguilliformes (61%) for FSHβ and of Cypriniformes (76%) for LHβ, followed by Siluriformes, 53% for FSHβ and 75% for LHβ. Interestingly, the identity with the corresponding human amino acid sequences was still remarkable: 45.1% for FSHβ and 51.4% for LHβ. Three dimensional models of ag-FSH and ag-LH, generated by using the crystal structures of h-FSH and h-LH as the respective templates and carried out via comparative modeling and molecular dynamics simulations, suggested the presence of the so-called "seat-belt", favored by a disulfide bond formed between the 3rd and 12th cysteine in both β-subunits. The sequences found will be used for the biotechnological synthesis of A. gigas gonadotrophic hormones (ag-FSH and ag-LH). In a first approach, to ascertain that the cloned transcripts allow the expression of the heterodimeric hormones, ag-FSH has been synthesized in human embryonic kidney 293 (HEK293) cells, preliminarily purified and characterized.

Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

Science.gov (United States)

Balasch, J; Vidal, E; Peñarrubia, J; Casamitjana, R; Carmona, F; Creus, M; Fábregues, F; Vanrell, J A

2001-08-01

It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and

Standardization of the radioimmunoassay of 17{beta}-estradiol (E{sub 2}) plasmatic and his application to the study of secretion of E{sub 2} in normal women, during the menstrual cycle and after the infusion of the gonadotropin (LH/FSH/RH) release factor; Padronizacao do metodo de radioimunoensaio de 17{beta}-estradiol (E{sub 2}) plasmatico e sua aplicacao ao estudo da secrecao de E{sub 2} em mulheres normais, durante o ciclo menstrual e apos a infusao do fator liberador de gonadotrofinas (LH/FSH/RH)

Energy Technology Data Exchange (ETDEWEB)

Kiyan, Takeko Shimizu

1979-07-01

A radioimmunoassay method for measurement of plasma E{sub 2} was standardized utilizing a highly specific antisera against E{sub 2} [-6 (-0-carboxymethyl)-oxime] BSA without the need of previous chromatographic purification. The anti-E{sub 2} serum was highly specific, showing high affinity with affinity constants: K{sub 1}=1 .62x10{sup 12} M{sup -1} and K{sub 2} = 2.94x10{sup 11} M{sup -1}, calculated by Scatchard plot. The standard curve sensitivity was 2 pico grams. The method was specific and accurate, showing an intra-assay precision with a mean C.V. of 2.9%, with the inter-assay evaluation showing a mean C.V. of 5.0%. This method was employed to evaluate E{sub 2} secretion during the menstrual cycle in 6 normal females, as indicated below: Days: -14 to -10 (early follicular phase..64.68 pg/ml{+-}12.14; - 9 to - 1(late follicular phase).122.39 pg/ml {+-}33,54; Peak day 281.28 pg/ml {+-}66 ,59; + 1 to + 7(early luteal phase) 127.47 pg/ml {+-}24.88; + 8 to +14 (late luteal phase) 87.57 pg/ml{+-}37,56. The effect of the acute and prolonged infusion of LH/FSH-RH(synthetic hypothalamic LH and FSH releasing hormone) was evaluated in the follicular and luteal phase in some of the normal females. (author)

An in vitro prototype of a porcine biomimetic testis-like cell culture system: a novel tool for the study of reassembled Sertoli and Leydig cells

Directory of Open Access Journals (Sweden)

Iva Arato

2018-01-01

Full Text Available At present, there is no reliable in vitro assembled prepubertal testis-like biomimetic organ culture system designed to assess the functional effects of human gonadotropins on Sertoli and Leydig cells. Spermatogenesis is regulated by endocrine, paracrine, and juxtacrine factors (testicular cross-talk, mainly orchestrated by gonadotropins such as luteinizing hormone (LH and follicle-stimulating hormone (FSH that play a pivotal role by stimulating Leydig and Sertoli cells, respectively. The aim of our study was to set up an in vitro prepubertal porcine bioengineered construct as a new model for experimental studies on reassembled Sertoli and Leydig cells. We have evaluated Sertoli and Leydig cells obtained from 15- to 20-day-old neonatal pig testes in terms of purity and function. Subsequently, purified Sertoli and enriched Leydig cells were subjected to coincubation to obtain an in vitro prepubertal porcine testis-like culture system. We performed enzyme-linked immunosorbent assay (ELISA for anti-Müllerian hormone (AMH, inhibin B, and testosterone secretion in the medium, and Real-Time PCR analysis of AMH, inhibin B, FSH-r, aromatase, LHr, and 3β-HSD mRNA expression levels. This in vitro testis-like system was highly responsive to the effects of human gonadotropins and testosterone. AMH mRNA expression and secretion declined, and inhibin-B increased, while FSH-receptor expression was downregulated upon FSH/LH exposure/treatment. Finally, the production of testosterone was increased selectively upon LH treatment. In summary, our proposed model could help to better determine the action of human gonadotropins on Sertoli and Leydig cells. The potential usefulness of the system for shedding light into male infertility-related issues is evident.

Basal follicle stimulating hormone and leptin on the day of hCG administration predict successful fertilization in in vitro fertilization

Directory of Open Access Journals (Sweden)

Andon Hestiantoro

2016-04-01

Full Text Available Background: Successful pregnancy in in vitro fertilization (IVF program depends on multiple factors. This study aimed to determine whether age, body mass index (BMI, basal follicle stimulating hormone (FSH, estradiol, and leptin on the day of trigger ovulation with human chorionic gonadotropin (hCG might be used as predictor for successful oocyte fertilization in in vitro fertilization (IVF program.Methods: This is a cross sectional study conducted in Yasmin Fertility Clinic, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Forty participating patients underwent IVF program, excluding smokers, patients with diabetic, morbid obesity, and severe oligospermia or azoospermia. Age, BMI, basal FSH, estradiol, leptin on the day of hCG administration, oocyte count on oocyte retrieval, the number of mature oocyte, and fertility rate were analyzed using bivariate and multivariate analysis to determine which eligible factors play role in predicting the successful of fertilization.Results: Significant correlation was found between basal FSH level and serum leptin/oocyte ratio on the day of hCG administration with successful fertilization. We found probability formula as follows: 1/(1+exp –(6.2 - 0.4(leptin serum/oocyte ratio - 0.8(basal FSH, with 77.8% sensitivity, 77.8% specificity, and AUC levels of 85.6% indicating strong predictability. Probability of successful fertilization related to basal FSH level of 5.90 mIU/mL and leptin serum/oocyte ratio of 3.98.Conclusion: The formula consisting of basal FSH and leptin serum/oocyte ratio on the day of trigger ovulation was capable in predicting the probability of successful fertilization in IVF procedure.

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

Science.gov (United States)

Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

2008-05-01

In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

Standardization of the radioimmunoassay of 17β-estradiol (E2) plasmatic and his application to the study of secretion of E2 in normal women, during the menstrual cycle and after the infusion of the gonadotropin (LH/FSH/RH) release factor

International Nuclear Information System (INIS)

Kiyan, Takeko Shimizu

1979-01-01

A radioimmunoassay method for measurement of plasma E 2 was standardized utilizing a highly specific antisera against E 2 [-6 (-0-carboxymethyl)-oxime] BSA without the need of previous chromatographic purification. The anti-E 2 serum was highly specific, showing high affinity with affinity constants: K 1 =1 .62x10 12 M -1 and K 2 = 2.94x10 11 M -1 , calculated by Scatchard plot. The standard curve sensitivity was 2 pico grams. The method was specific and accurate, showing an intra-assay precision with a mean C.V. of 2.9%, with the inter-assay evaluation showing a mean C.V. of 5.0%. This method was employed to evaluate E 2 secretion during the menstrual cycle in 6 normal females, as indicated below: Days: -14 to -10 (early follicular phase..64.68 pg/ml±12.14; - 9 to - 1(late follicular phase).122.39 pg/ml ±33,54; Peak day 281.28 pg/ml ±66 ,59; + 1 to + 7(early luteal phase) 127.47 pg/ml ±24.88; + 8 to +14 (late luteal phase) 87.57 pg/ml±37,56. The effect of the acute and prolonged infusion of LH/FSH-RH(synthetic hypothalamic LH and FSH releasing hormone) was evaluated in the follicular and luteal phase in some of the normal females. (author)

Characterization of monoclonal antibodies directed against human thyroid stimulating hormone

International Nuclear Information System (INIS)

Soos, M.; Siddle, K.

1982-01-01

Monoclonal antibodies directed against human thyroid stimulating hormone (TSH) were obtained from hybrid myelomas, following fusion of mouse NSI myeloma cells with mouse spleen cells. Ten different antibodies were obtained from 4 separate fusions. Eight antibodies were of the IgG 1 subclass. Affinities of antibodies for TSH were in the range 2 x 10 8 -5 x 10 10 M -1 . Five of the antibodies were specific for TSH and did not react with LH, FSH or hCG. The remaining antibodies reacted with all these hormones and were assumed to recognise their common (α) subunit. The 5 specific antibodies fell into 3 subgroups recognising distinct antigenic determinants, whereas the 5 non-specific antibodies recognised a single determinant or closely related set of sites. It is concluded that these antibodies should be valuable reagents for use in sensitive and specific two-site immunoradiometric assays. (Auth.)

Analysis of recombinant and native human lutropin/luteotrophin and human chorionic gonadotropin by reversed-phase high performance liquid chromatography; Analise de luteotrofina humana e de gonadotrofina corionica humana, recombinante e natural, por cromatografia liquida de alta eficiencia em fase reversa

Energy Technology Data Exchange (ETDEWEB)

Almeida, Beatriz Elane de

2009-07-01

Specific RP-HPLC conditions for the analysis of recombinant and native hLH and hCG preparations and of their subunits were set up. Heterodimeric hLH and hCG and their alpha and beta subunits all migrated with significantly different retention times (t{sub R}) in the following order of increasing hydrophobicity: alpha-hCG < alpha-hLH < hCG < hLH < -beta-hCG < beta-hLH. With basis on these conditions, a total of eleven preparations were studied: the International Standard of recombinant hLH-WHO 96/602, a commercial recombinant and two highly purified pituitary hLH, a recombinant and two urinary hCG preparations and four heterogeneous urinary products containing hLH + hFSH. All hLH preparations showed very similar retention times for the main peak (t{sub R} = 38.35 +- 0.42 min; RSD = 1.1 %; n = 4 preparations), while the hCG main peak ran about 4 % faster when compared to this average value. Human LH, hFSH and hCG peaks could also be identified in the heterogeneous urinary preparations. Quantitative analysis could be validated for the seven homogeneous preparations and accuracy, precision and sensitivity were calculated on the basis of a highly linear dose-response curve (r=0.99998; p<0.0001; n=20). Quantification of the different gonadotropins in the heterogeneous urinary preparations was also carried out, though with clear accuracy limitations. (author)

Analysis of the kinetics of ovine follitropin agonist-antagonist interactions with pig ovarian membranes

Energy Technology Data Exchange (ETDEWEB)

Sebok, K.; De Lean, A.; Sairam, M.R.

1987-06-16

The binding of /sup 125/I-labeled ovine follitropin (oFSH) and /sup 125/I-labeled deglycosylated ovine follitropin (DG-oFSH) to porcine granulosa cell membranes was studied at equilibrium and nonequilibrium binding conditions and statically analyzed. Saturation and competition binding experiments revealed homogeneity in the population of binding sites labeled with /sup 125/I-oFSH, having a pK estimation of approx.10. /sup 125/I-DG-oFSH similarly interacts with a single uniform class of receptors of equal affinity (pK approx. 10) and binding capacity as oFSH. In contrast, displacement experiments using /sup 125/I-DG-oFSH as tracer and unlabeled oFSH as competing ligand demonstrate slope factors less than unity, suggesting apparent heterogeneity of sites not observed with /sup 125/I-DG-oFSH vs. DG-oFSH competition experiments. Under these conditions, it appears that FSH binds to two sites in near equal proportion but of unequal affinities. The total specific binding capacities of these sites equal those observed in /sup 125/I-DG-oFSH/unlabeled DG-oFSH competition experiments. Analysis of oFSH association kinetics at 37 /sup 0/C by curve-fitting methods is best explained by a biexponential rate equation describing a fast and a slow association component that are equally distributed. DG-oFSH demonstrates a disproportionately greater amount of fast vs. slow binding component. Dissociation, promoted by the same unlabeled hormone, of bound /sup 125/I-DG-oFSH and /sup 125/I-oFSH induces biphasic kinetics consisting of a fast and a slow dissociable pool of prebound tracer. Computer analysis reveals that both tracers dissociate with similar fast t/sub 1/2/ times; however, DG-oFSH exhibited a t/sub 1/2/ approximately 2 times slower for the component vs. oFSH. From this study, it is concluded that oFSH and DG-oFSH bind to the receptor(s) in a complex reaction scheme, more so for oFSH than DG-oFSH.

Human ovolution and plasma oxytocin

International Nuclear Information System (INIS)

Kumaresan, Perianna; Kumaresan, Malathi; Hossini, Mahmood; Arellano, Carolina; Vasicka, Alois

1983-01-01

Plasma oxytocin (OT) concentrations were measured by radioimmunoassay (RIA) method without extracting plasma in 11 normal menstruating women. Mean plasma OT level began to increase steadily from the 7th day of the menstrual cycle and this level rose up to 20+-5 μU/ml (Mean+-S.E.) on the 10th day of the cycle. OT level declined to 13+-6 μU/ml on the day of the LH peak and continuously declined for another 2 days - then rose. The OT level was higher during the follicular phase than during the luteal phase. In 1 individual OT measured in 2 cycles a year apart showed the highest level of OT coincided with LH and FSH peak and abruptly declined. When there was the highest level of progesterone, the OT level was measurable 1 out of 11 cycles. From this study, we conclude that OT may have a role in human ovulation either synergistically or alone with other ovulatory mechanisms and ovarian estradiol and progesterone control the secretion of OT and also suggests that OT may play some role in the regulation of the luteolysis and the menstrual cycle in women. (author)

Expression and localization of the progesterone receptor in mouse and human reproductive organs

DEFF Research Database (Denmark)

Teilmann, Stefan Cuoni; Clement, Christian Alexandro; Thorup, Jørgen

2006-01-01

examined, primary granulosa cell cilia lacked PR staining. SDS-PAGE and western blotting analysis of tissues from oviduct, uterus, and ovary confirmed antibody specificity, and identified two bands corresponding to the PR isoforms PR-A and PR-B. Upon hCG stimulation, a new band cross-reacting with anti......-PR emerged above the PR-A form in oviduct fractions, suggesting LH-induced phosphorylation of PR-A. We suggest that ciliary PR in the oviduct plays a role in progesterone signaling after ovulation, possibly via non-genomic events. These novel findings warrant further studies of oviduct and postovulatory...... were unstained or faintly stained. Pubertal female mice were further studied by confocal laser scanning microscopy and western blotting before and after injection with FSH and LH followed by human chorionic gonadotropin (hCG) injection after a 48-h period. PR immunolocalization to the oviduct cilia...

Endocrine gland derived-VEGF is down-regulated in human pituitary adenoma.

Science.gov (United States)

Raica, Marius; Coculescu, Mihail; Cimpean, Anca Maria; Ribatti, Domenico

2010-10-01

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic molecule restricted to endocrine glands and, particularly, to steroid-secreting cells. The expression of EG-VEGF and its significance in human adenohypophysis in physiological and pathological conditions is still unknown. In this study, we investigated by immunohistochemistry the expression of EG-VEGF in 2 samples of normal adenohypophysis and 43 bioptic samples of pituitary adenoma. Moreover, the expression of growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and adrenocorticoprophic hormone (ACTH) were also estimated. The results of this study for the first time demonstrate a down-regulation of EG-VEGF expression in human pituitary adenoma as compared to normal adenohypophysis, suggesting an impaired function of the neoplastic cells in terms of hormone release in the blood stream, as a consequence of impaired tumor angiogenesis in the tumor. On the basis of our data showing a marked decrease in the expression of EG-VEGF in pituitary adenoma, with the exception of LH-secreting adenomas, we suggest that LH might be involved in the induction of EG-VEGF secretion.

Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH+LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome.

Science.gov (United States)

Dubourdieu, Sophie; Fréour, Thomas; Dessolle, Lionel; Barrière, Paul

2013-05-01

To compare the efficacy of pulsatile GnRH therapy versus combined gonadotropins for ovulation induction in women with both hypothalamic amenorrhoea and polycystic ovarian syndrome (HA/PCOS) according to their current hypothalamic status. This single-centre, prospective, randomized study was conducted in the Nantes University Hospital, France. Thirty consecutive patients were treated for ovulation induction with either pulsatile GnRH therapy or combined gonadotropins (rFSH+rLH). Frequency of adequate ovarian response (mono- or bi-follicular) and clinical pregnancy rate were then compared between both groups. Ovarian response was similar in both groups with comparable frequency of adequate ovarian response (73% vs 60%), but the clinical pregnancy rate was significantly higher in the pulsatile GnRH therapy group than in the combined gonadotropin group (46% vs 0%). HA/PCOS is a specific subgroup of infertile women. Pulsatile GnRH therapy is an effective and safe method of ovulation induction that can be used successfully in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Production of specific antisera for radioimmunoassay of human luteinizing hormone (LH) in the presence of human chorionic gonadotropin (hCG)

International Nuclear Information System (INIS)

Thorell, J.I.; Jeppsson, S.; Holmstrom, B.

1976-01-01

A specific radioimmunoassay for LH, which measures plasma LH in the presence of human chorionic gonadotropin (hCG) is described. Rabbits were immunized with highly purified native LH. One of the antisera with a difference in its reactivity against LH and hCG was further purified by affinity chromatography on a column with hCG coupled to Sepharose 4B. The adsorbed antiserum and 125 I-LH was used in a double antibody assay. The LH standard (MRC/68/40) efficiently inhibited the binding of 125 I-LH, and the standard curve showed a sensitivity of 0.5 ng/ml in the sample. hCG up to 10,000 ng/ml did not inhibit the binding of 125 I-LH. The plasma level of LH in pregnant women in the first trimester was low (1.3 +- 0.1 ng/ml). When LH was measured in fertile or menopausal women with or without stimulation with LH/FSH releasing hormone (LH-RH)/sup x/ the results agreed to those found with our conventional LH-assay based on antiserum against hCG

Reduced Seminal Concentration of CD45pos Cells after Follicle-Stimulating Hormone Treatment in Selected Patients with Idiopathic Oligoasthenoteratozoospermia

Directory of Open Access Journals (Sweden)

Rosita A. Condorelli

2014-01-01

Full Text Available The present study evaluated the conventional sperm parameters and the seminal concentration of CD45pos cells (pan-leukocyte marker of infertile patients with idiopathic oligoasthenoteratozoospermia (OAT. The patients were arbitrarily divided into three groups treated with recombinant follicle-stimulating hormone FSH: α (Group A = 20 patients, recombinant FSH-β (Group B = 20 patients, and highly purified human FSH (Group C = 14 patients. All treated groups achieved a similar improvement of the main sperm parameters (density, progressive motility, and morphology, but only the increase in the percentage of spermatozoa with normal morphology was significant compared to the baseline in all three examined groups. Moreover, all groups had a significant reduction of the seminal concentration of CD45pos cells and of the percentage of immature germ cells. Before and after the treatment, the concentration of CD45pos cells showed a positive linear correlation with the percentage of immature germ cells and a negative correlation with the percentage of spermatozoa with regular morphology. These results demonstrate that treatment with FSH is effective in patients with idiopathic OAT and that there are no significant differences between the different preparations. The novelty of this study is in the significant reduction of the concentration of CD45pos cells observed after the treatment.

Recombinant follitropin alfa/lutropin alfa in fertility treatment

Directory of Open Access Journals (Sweden)

Ahmed Gibreel

2009-12-01

Full Text Available Ahmed Gibreel1, Siladitya Bhattacharya21School of Medicine and Dentistry, University of Aberdeen; 2Aberdeen Maternity Hospital, Aberdeen, UKAbstract: Recombinant human follicle stimulating hormone (rFSH and luteinizing hormone (LH, also known as follitropin alpha and lutropin alpha, are manufactured by genetic engineering techniques which ensure high quality and batch to batch consistency. Follitropin alpha can be used for controlled ovarian hyperstimulation in assisted reproduction, ovulation induction for WHO group I and II anovulatory infertility and in men with hypogonadotrophic hypogonadism (HH or idiopathic oligo-asthenospermia. Current evidence suggests superiority of urinary human menopausal gonadotropin (HMG over follitropin alpha in controlled ovarian hyperstimulation for IVF in terms of live birth rate per couple. Addition of lutropin to follitropin alpha in an unselected IVF population does not appear to confer any benefit; however, it may have a role in ovulation induction in women with hypothalamic hypogonadism. Urinary HMG preparations (especially currently available highly purified preparations are more cost effective than rFSH in terms of cost per ongoing pregnancy. However, women using rFSH injection pen devices have higher levels of satisfaction as compared to those using urinary HMG by means of conventional syringes.Keywords: infertility, follicle stimulating hormone, luteinizing hormone, follitropin alpha, lutropin alpha, in-vitro fertilization, urinary gonadotrophins

Cost-effectiveness of short COH protocols with GnRH antagonists using different types of gonadotropins for in vitro fertilization

Directory of Open Access Journals (Sweden)

Guenka Petrova

2016-05-01

Full Text Available The aim of this study was to explore the cost-effectiveness of short protocols including different types of gonadotropins for controlled ovarian hyperstimulation (COH for in vitro fertilization (IVF. A retrospective, observational study of the real-life practice in a specialized IVF gynaecology clinic in 2009–2013 was carried out. All women on short COH protocols were recruited into three groups: COH including recombinant follicle stimulating hormone (rFSH and urinary-FSH (urFSH (n = 173; including urFSH alone (n = 289; and including rFSH alone (n = 212. The cost-effectiveness of the COH protocols was explored in two different case scenarios for possible outcomes. The first case scenario took into consideration a successful live birth, and the second one, the women to achieve pregnancy with live birth. Decision modelling was done using the TreeAge 2014 Software. According to the results in the first case scenario, the rFSH plus urFSH COH approach showed the highest weighted probability (p = 0.38 of live birth, but the urFSH alternative was cost-effective. The results in the second case scenario demonstrated that the urFSH protocol was again the cost-effective alternative. These results suggest that the strategy with urFSH should be preferred in both cases, but rFSH could also be considered as a cost-effective alternative for successful live birth and achieving pregnancy and delivery, since the incremental cost-effectiveness ratio in comparison with the urFSH protocol is below the gross domestic product per capita. The combined approach of rFSH and urFSH was shown not to be cost-effective in both explored scenarios.

Testicular function following irradiation of the human prepubertal testis

International Nuclear Information System (INIS)

Shalet, S.M.; Beardwell, C.G.; Jacobs, H.S.; Pearson, D.

1978-01-01

Testicular function was studied in ten men, aged between 17 and 36 years, who had received irradiation for a nephroblastoma during childhood. The dose of scattered irradiation to the testes ranged from 268 to 983 rad. Eight subjects had either oligo-or azoosperma (0 to 5.6 million/ml), seven of whom had an elevated serum follicle stimulating hormone (FSH) level. One subject showed evidence of Leydig cell dysfunction with a raised serum luteinizing hormone level (LH) and a low plasma testosterone concentration. A second group of eight prepubertal males, aged between 8 and 14 years, were studied. These had also been irradiated for abdominal malignancies during childhood and received a similar dose of irradiation to the testis as the first group studied. The plasma testosterone levels were within the normal range in all eight. The mean gonadotropin levels were not significantly different from normal. Thus irradiation-induced damage to the germinal epithelium in prepubertal boys raised FSH levels after puberty but not before it. The conclusion is that inhibin has a minor role in the control of the pre-pubertal hypothalmic-pituitary testicular axis and its contribution to gonadal control of gonadotrophin secretion changes with sexual maturation. (author)

Direct antigonadal activity of cannabinoids: suppression of rat granulosa cell functions.

Science.gov (United States)

Adashi, E Y; Jones, P B; Hsueh, A J

1983-02-01

The direct effects of delta 9-tetrahydrocannabinol (THC) and related cannabinoids on ovarian granulosa cells were studied in vitro. Granulosa cells from immature, hypophysectomized, estrogen-treated rats were cultured for 2 days in an androstenedione-supplemented medium in the presence or absence of follicle-stimulating hormone (FSH) (10 ng/ml) with or without cannabinoids. FSH treatment increased progesterone and estrogen biosynthesis, whereas concomitant treatment with THC led to a dose-dependent inhibition of the FSH-stimulated accumulation of progesterone and estrogen with ED50 values of 3.5 +/- 0.3 X 10(-7) and 1.8 +/- 0.2 X 10(-6) M, respectively. Treatment with related but nonpsychoactive cannabinoids (cannabidiol, cannabinol, cannabigerol, or cannabichromene) was equally effective. The THC-induced inhibition of progesterone production was reversible and was associated with an inhibition of pregnenolone biosynthesis and a decrease of 3 beta-hydroxysteroid dehydrogenase activity. In addition, treatment with THC brought about a dose-dependent inhibition of the FSH-induced increase in luteinizing hormone (LH) receptors. The inhibitory effects of THC were not associated with changes in cell number, protein content, or cell viability. Thus, THC exerts direct inhibitory effects on FSH-dependent functions related to steroidogenesis and the acquisition of LH receptors, all of which are essential to follicular maturation. Because plasma concentrations of THC similar to those used in this study have been reported in human beings, repeated exposure of female users to THC may lead to ovarian dysfunction, due in part, to the direct antigonadal activity to THC.

Correction

Directory of Open Access Journals (Sweden)

2012-01-01

Full Text Available Regarding Gorelik, G., & Shackelford, T.K. (2011. Human sexual conflict from molecules to culture. Evolutionary Psychology, 9, 564–587: The authors wish to correct an omission in citation to the existing literature. In the final paragraph on p. 570, we neglected to cite Burch and Gallup (2006 [Burch, R. L., & Gallup, G. G., Jr. (2006. The psychobiology of human semen. In S. M. Platek & T. K. Shackelford (Eds., Female infidelity and paternal uncertainty (pp. 141–172. New York: Cambridge University Press.]. Burch and Gallup (2006 reviewed the relevant literature on FSH and LH discussed in this paragraph, and should have been cited accordingly. In addition, Burch and Gallup (2006 should have been cited as the originators of the hypothesis regarding the role of FSH and LH in the semen of rapists. The authors apologize for this oversight.

[In vitro fertilization in France: economic aspects and influence of the gonadotropin choice (urinary vs. recombinant) on cost].

Science.gov (United States)

de Mouzon, J; Allavena, E; Schmitt, C; Frappé, M

2004-06-01

The objective of the study was to make an economic evaluation of in vitro fertilization and to determine the impact of some factors on its cost, particularly the choice between recombinant follicle stimulating hormone (r-FSH) and urinary FSH (u-FSH) for ovarian stimulation. Costs were calculated in a Public Health view, by studying two phases: the stimulation cycle (including down-regulation) and the pregnancy (including the neonatal period). The calculation has included the side effects and the frozen embryos transfers. Economic data came from various sources: the French nomenclature on medical treatments (NGAP), the French drugs dictionary (Vidal) and the French Information system medical plan (PMSI). FSH costs were computed according to the currently marketed products, i.e., Fostimon (Laboratoires Genévrier, Sophia-Antipolis, France) for urinary FSH, and Gonal-F (Laboratoires Serono, Boulogne-Billancourt, France) and Puregon (Laboratoires Organon, Puteaux, France) for recombinant FSH. Two different ways of efficacy between u-FSH and r-FSH were considered for the calculations, those reported in Daya's meta-analysis (3.7% in favour of r-FSH for the clinical pregnancy rate per initiated cycle) and in the only double-blind study (Frydman et al., no difference). The annual cost of ART reaches approximately 130 million Euros in France, for the cycles only, and 170 million Euros when including the pregnancy costs. Urinary FSH is much cheaper than recombinant FSH. Whereas the number of administered FSH units was higher in u-FSH, this results in a mean lower cost of 500 Euros per cycle (2422 Euros for u-FSH and 2959 Euros for r-FSH). For one complete year, in France, the potential over cost of recombinant products reaches 24 million Euros when considering only the cycles (128.4 vs. 104.0 million Euros) and 24-31 million Euros when pregnancies and babies (neonatal period) are considered (171.4 vs 140.7 and 147.0 million Euros, respectively). The IVF per baby cost can be

Morphological markers to select populations of oocytes with different cultural needs for dedicated pre-maturation protocols

Directory of Open Access Journals (Sweden)

Cecilia Dieci

2017-05-01

Full Text Available Oocyte’s chromatin gradually becomes more compacted during the final stage of oocyte development and the level of chromatin compaction is considered a marker of oocyte differentiation [Luciano et al, 2014]. Moreover, several studies demonstrate that in vitro pre-maturation treatments (Pre-IVM, aimed to improve the developmental capability of immature oocytes, might behave differently depending on the oocyte metabolic status, when it is isolated from follicle [Luciano et al., 2011]. This study aims at identifying correlations between cumulus-oocyte complex (COC morphology and oocyte chromatin configuration and secondly at testing the hypothesis that only fully grown oocytes at earlier stages of differentiation with loosely compacted chromatin  (GV1 can benefit from Pre-IVM treatment.   COCs were collected from bovine 2-6mm ovarian follicles, and further divided in three groups according to their morphology (Class-1, 2 and 3 as previously described [Blondin & Sirard, 1995]. Analysis of chromatin configuration revealed that only Class-1 COC was enriched in GV1 oocyte, while Class-2 and 3 presented a similar distribution of GV1, GV2 and GV3 oocytes, where GV2 and 3 oocytes are characterized by increased chromatin compaction [Lodde et al., 2007]. Then COCs were divided into two groups, one containing Class-1 COCs and the other containing Class-2 and 3 COCs and subjected to pre-IVM for 6 hours in presence of cilostamide and 10-4 UI/ml rhFSH. Finally, COCs underwent standard in vitro maturation (IVM for 22 hours, in vitro fertilization and embryo culture. Blastocyst rate and embryos cell number were assessed at day 7. Pre-IVM positively affected developmental competences of Class-1, while in Classes 2 and 3 Pre-IVM had detrimental effects.In conclusion COCs morphology could be used as a non-invasive approach to select population of oocyte with different cultural needs. These data could be useful in setting-up dedicated IVM protocols considering

Radioimmunological determination of follicle stimulating hormone in the serum of patients with various gonadal disturbances

International Nuclear Information System (INIS)

Otte, P.

1982-01-01

A new kit for FSH determination in the serum was tested: the precision, sensitivity and specificity of this kit were adequate. With 185 men and 99 women with various hypophyseal and gonadal disorders the serum FSH was determined in radioimmunoassay as a supplement for diagnostic. Patients with hypophyseal tumors had to some extent pre-operatively increased and after hypophysectomy in general subnormal FSH values. Male patients with primary hypogonadism had without substitution therapy inclusively distinct to pronounced FSH level increases. With young patients with gynecomastia FSH values which lay primarily in the normal range were measured. Female patients with primary ovarial insufficiency often indicated very sharp increases in FSH levels. Female patients with Turner syndrome showed high FSH values at puberty age. In girls with hyposomia and hypogonadism high FSH levels refer accordingly to such a syndrome. (orig.) [de

The Effect of Human Chorionic Gonadotropin Treatment Before Testicular Sperm Extraction in Non-Obstructive Azoospermia

Directory of Open Access Journals (Sweden)

Ümit Gul

2014-12-01

Full Text Available Aim: To investigate our experience on empirical hCG treatment of patients with idiopathic non-obstructive azoospermia (NOA. Material and Method: hCG group consisted of 34 patients who were empirically treated with hCG despite normal serum FSH and LH levels and normal testicular volumes. hCG was administered as 2500 IU twice weekly subcutaneous injections for 10 to 14 weeks prior to testicular sperm extraction (TESE. Control group consisted of 49 age and spouse age matched patients who underwent TESE in the same time period. Sperm retrieval rate (SRR, and follicle stimulating hormone (FSH, lutenizing hormone (LH and testosterone levels, volume of testicles, fertilization rate (FR, implantation rate (IR, pregnancy rate (PR, live birth rate (LBR and cancel rate (CR and surgical technique were compared between the two groups. Results: Conventional technique was used in 14 of the 17 patients (82.3% with successful sperm retrieval in the hCG group, and 18 of the 28 patients (64.3% in the control group (p=0.170. There were no differences between groups in terms of SRR (p=0.338. There were no significant differences in patient age, mean infertility period, mean values of FSH, LH, testosterone, estradiol levels, and testis volume between the two groups (p>0.05. There were no statistically significant differences for FR, IR, PR, LBR between the two groups (p>0.05. Discussion: Empirical hCG treatment in patients with idiopathic NOA did not result in improved SRR. hCG treatment did not have any effect on the success of ICSI.

The Human Experience With Ghrelin Administration

Science.gov (United States)

Garin, Margaret C.; Burns, Carrie M.; Kaul, Shailja

2013-01-01

Context: Ghrelin is an endogenous stimulator of GH and is implicated in a number of physiological processes. Clinical trials have been performed in a variety of patient populations, but there is no comprehensive review of the beneficial and adverse consequences of ghrelin administration to humans. Evidence Acquisition: PubMed was utilized, and the reference list of each article was screened. We included 121 published articles in which ghrelin was administered to humans. Evidence Synthesis: Ghrelin has been administered as an infusion or a bolus in a variety of doses to 1850 study participants, including healthy participants and patients with obesity, prior gastrectomy, cancer, pituitary disease, diabetes mellitus, eating disorders, and other conditions. There is strong evidence that ghrelin stimulates appetite and increases circulating GH, ACTH, cortisol, prolactin, and glucose across varied patient populations. There is a paucity of evidence regarding the effects of ghrelin on LH, FSH, TSH, insulin, lipolysis, body composition, cardiac function, pulmonary function, the vasculature, and sleep. Adverse effects occurred in 20% of participants, with a predominance of flushing and gastric rumbles and a mild degree of severity. The few serious adverse events occurred in patients with advanced illness and were not clearly attributable to ghrelin. Route of administration may affect the pattern of adverse effects. Conclusions: Existing literature supports the short-term safety of ghrelin administration and its efficacy as an appetite stimulant in diverse patient populations. There is some evidence to suggest that ghrelin has wider ranging therapeutic effects, although these areas require further investigation. PMID:23533240

Characterization of follicle stimulating hormone profiles in normal ovulating women.

Science.gov (United States)

Ecochard, René; Guillerm, Agnes; Leiva, René; Bouchard, Thomas; Direito, Ana; Boehringer, Hans

2014-07-01

To describe FSH profile variants. Observational study. Multicenter collaborative study. A total of 107 women. Women collected daily first morning urine and underwent serial ovarian ultrasound. The individual FSH cyclic profiles demonstrated a significant departure from the currently accepted model. A decline in FSH levels at the end of the follicular phase was observed in only 42% of cycles. The absence of this decline was significantly associated with a shorter luteal phase and higher pregnanediol-3α-glucuronide, FSH, and LH levels at the time of ovulation. In 34% of the cycles, significant FSH variability was observed throughout the follicular phase; this variability was associated with higher body mass index and lower overall FSH and LH levels throughout the cycle. The FSH peak occurs on average 2 hours before ovulation. The FSH peak duration was shorter than the LH peak. These results suggest that average FSH profiles may not reflect the more complex dynamics of daily hormonal variations in the menstrual cycle. It is possible that discrepancies between the average normal FSH profile and the individual day-to-day variants can be used to detect abnormalities. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Characterization of monoclonal antibodies against human thyrotropin and use in an immunoradiometric assay and immunohistochemistry

International Nuclear Information System (INIS)

Benkirane, M.; Bon, D.; Bellot, F.; Prince, P.; Delori, P.; Hassoun, J.; Carayon, P.

1987-01-01

Monoclonal antibodies were prepared against human thyrotropin. 13 different antibodies were characterized. Ten antibodies were of the IgG1 subclass. The affinities of the antibodies were in the range 10 9 -10 11 mol -1 .l. Four of them were specific for hTSH and did not react with hLH, hFSH, hCG or αhCG. Four reacted with these hormones and recognized the α subunit of hCG. One cross-reacted only with HFSH. The remaining four antibodies recognized the holo-hTSH only, and thus were designated as anti-conformational determinants. Monoclonal antibodies reacting with different antigenic determinants on the hTSH molecule defined seven clusters. Two of them were used to develop a simplified two-site sandwich radioimmunoassay in which one monoclonal antibody was immobilized on tubes (anti-βTSH) and another (anti-α) labelled with 125 I. This assay was highly specific and demonstrated a sensitivity level of 0.1 μIU/ml. Two monoclonal antibodies were used in immunohistochemistry and their quality and specificity was assessed in the detection of hTSH immunoreactivity in human pituitary biological sections. 20 refs.; 6 figs.; 2 tabs

Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model

Energy Technology Data Exchange (ETDEWEB)

Geng, Wenxin; Yan, Xingrong; Du, Huicong; Cui, Jihong; Li, Liwen, E-mail: liven@nwu.edu.cn; Chen, Fulin, E-mail: chenfl@nwu.edu.cn

2013-05-03

Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal α and β estrogen receptor null mice were only mildly osteopenic, and mice with either receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSHβ fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSHβ antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women.

Investigation of a thiazolidinone derivative as an allosteric modulator of follicle stimulating hormone receptor: evidence for its ability to support follicular development and ovulation.

Science.gov (United States)

Sriraman, Venkataraman; Denis, Deborah; de Matos, Daniel; Yu, Henry; Palmer, Stephen; Nataraja, Selva

2014-05-15

FSH signalling through its cognate receptor is critical for follicular development and ovulation. An earlier study had documented thiazolidinone derivatives to activate FSH receptor expressed in CHO cells and rat granulosa cells; however development of this compound for clinical use was halted for unobvious reasons. The objective of the current study is to extend the previous investigations in detail on the ability of thiazolidinone derivative (henceforth referred to as Compound 5) to activate FSH signalling and learn the barriers that preclude development of this derivative for clinical purposes. Our results demonstrate that the Compound 5 in a dose-dependent manner stimulated cAMP production, activated AKT and ERK signalling pathways and induced estradiol production in cultured rat granulosa cells. Compound 5 also caused dose-dependent increase in estradiol production from human granulosa cells. In increasingly more complex in vitro systems, Compound 5 was able to induce the expansion of mouse cumulus-oocyte-complex and support in vitro development of mouse preantral follicle to preovulatory stage and release of oocyte from the follicle. In vivo, the compound stimulated preovulatory follicular development and ovulation in immature rats. Pharmacokinetic and safety investigations reveal poor oral availability and genotoxicity. Together, our results document Compound 5 to act as a FSHR allosteric modulator but have poor pharmacological properties for development of an oral FSH receptor modulator. Copyright © 2014 Elsevier Inc. All rights reserved.

Dual effect of insulin resistance and cadmium on human granulosa cells - In vitro study

Energy Technology Data Exchange (ETDEWEB)

Belani, Muskaan, E-mail: muskaanbelani@gmail.com [Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India. (India); Shah, Preeti, E-mail: preeti.shah@novaivifertility.com [Nova IVI Fertility, Behind Xavier' s Ladies Hostel, 108, Swastik Society Rd., Navrangpura, Ahmedabad 390009, Gujarat, India. (India); Banker, Manish, E-mail: manish.banker@novaivifertility.com [Nova IVI Fertility, Behind Xavier' s Ladies Hostel, 108, Swastik Society Rd., Navrangpura, Ahmedabad 390009, Gujarat, India. (India); Gupta, Sarita, E-mail: saritagupta9@gmail.com [Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India. (India)

2016-12-15

Combined exposure of cadmium (Cd) and insulin resistance (IR) might be responsible for subfertility. In the present study, we investigated the effects of Cd in vitro in IR human granulosa cells. Isolated human granulosa cells from control and polycystic ovary syndrome (PCOS) follicular fluid samples were confirmed for IR by decrease in protein expression of insulin receptor-β. Control and IR human granulosa cells were then incubated with or without 32 μM Cd. The combined effect of IR with 32 μM Cd in granulosa cells demonstrated significant decrease in expression of StAR, CYP11A1, CYP19A1, 17β-HSD, 3β-HSD, FSH-R and LH-R. Decrease was also observed in progesterone and estradiol concentrations as compared to control. Additionally, increase in protein expression of cleaved PARP-F2, active caspase-3 and a positive staining for Annexin V and PI indicated apoptosis as the mode of increased cell death ultimately leading to decreased steroidogenesis, as observed through the combined exposure. Taken together the results suggest decrease in steroidogenesis ultimately leading to abnormal development of the follicle thus compromising fertility at the level of preconception. - Highlights: • Protein expression of INSR-β in granulosa cells to differentiate PCOS-IR and NIR • Cd and IR together decrease steroidogenesis in human granulosa cells in vitro. • Cd and IR increase human granulosa cell death by increase in apoptosis. • Environment and life style are set to hamper pregnancies at preconception level.

Dual effect of insulin resistance and cadmium on human granulosa cells - In vitro study

International Nuclear Information System (INIS)

Belani, Muskaan; Shah, Preeti; Banker, Manish; Gupta, Sarita

2016-01-01

Combined exposure of cadmium (Cd) and insulin resistance (IR) might be responsible for subfertility. In the present study, we investigated the effects of Cd in vitro in IR human granulosa cells. Isolated human granulosa cells from control and polycystic ovary syndrome (PCOS) follicular fluid samples were confirmed for IR by decrease in protein expression of insulin receptor-β. Control and IR human granulosa cells were then incubated with or without 32 μM Cd. The combined effect of IR with 32 μM Cd in granulosa cells demonstrated significant decrease in expression of StAR, CYP11A1, CYP19A1, 17β-HSD, 3β-HSD, FSH-R and LH-R. Decrease was also observed in progesterone and estradiol concentrations as compared to control. Additionally, increase in protein expression of cleaved PARP-F2, active caspase-3 and a positive staining for Annexin V and PI indicated apoptosis as the mode of increased cell death ultimately leading to decreased steroidogenesis, as observed through the combined exposure. Taken together the results suggest decrease in steroidogenesis ultimately leading to abnormal development of the follicle thus compromising fertility at the level of preconception. - Highlights: • Protein expression of INSR-β in granulosa cells to differentiate PCOS-IR and NIR • Cd and IR together decrease steroidogenesis in human granulosa cells in vitro. • Cd and IR increase human granulosa cell death by increase in apoptosis. • Environment and life style are set to hamper pregnancies at preconception level.

Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation

Directory of Open Access Journals (Sweden)

Paraskevis Dimitris

2009-10-01

Full Text Available Abstract A simple, safe and cost-effective treatment protocol in ovarian stimulation is of great importance in IVF practice, especially in the case of previous unsuccessful attempts. hCG has been used as a substitute of LH because of the degree of homology between the two hormones. The main aim of this prospective randomized study was to determine, for the first time, whether low dose hCG added to rFSH for ovarian stimulation could produce better results compared to the addition of rLH in women entering IVF-ET, especially in those women that had previous IVF failures. An additional aim was to find an indicator that would allow us to follow-up ovarian stimulation and, possibly, modify it in order to achieve a better IVF outcome; and that indicator may be the cDNA copies of the LH/hCG receptor. Group A patients (n = 58 were administered hCG and Group B rLH (n = 56 in addition to rFSH in the first days of ovarian stimulation. The number of follicles and oocytes and, most importantly, implantation and pregnancy rates were shown to be statistically significantly higher in the hCG group. This study has also determined, for the first time to our best knowledge, m-RNA for LH/hCG receptors in the lymphocytes of peripheral blood 40 h before ovum pick-up. cDNA levels of the hCG receptor after ovarian stimulation were significantly higher among women receiving hCG compared to those receiving LH. In addition, higher levels were encountered among women with pregnancy compared to those without, although this was not statistically significant due to the small number of pregnancies. It seems that hCG permits a highly effective and more stable occupancy of rLH/hCG receptors and gives more follicles and more oocytes. The determination of cDNA copies could be, in the future, a marker during ovulation induction protocols and of course a predictor for the outcome of ART in the special subgroup of patients with previous failures.

Studies on luteinizing hormone receptors of human corpora lutea during menstrual cycle and pregnancy

International Nuclear Information System (INIS)

Izumi, Yasushi

1982-01-01

With the purpose of explicating the lifespan of human corpora lutea, using human corpora lutea of the menstrual cycle and pregnancy, binding of 125 I-LH to the 20,000g cell membrane fraction was examined. 1) Specific bindings of 125 I-LH, 125 I-HCG were demonstrated in the 20,000g cell membrane fraction. Although LH and HCG were parallel in inhibiting 125 I-LH binding, HCG was found to be more effective. FSH did not inhibit binding. 2) Binding of 125 I-LH was dependent on time, temperature, 125 I-LH concentration, amount of the cell membrane fraction protein and pH. The highest binding was seen at pH 6.0 while incubating for 60 min at 37 0 C. 3) The number of LH receptors in human corpora lutea of the menstrual cycle increased towards midluteal phase, especiallt on 5th day from ovulation, and decreased towards late luteal phase. LH receptor was not found in corpus albicans. The apparent dissociation constant of each corpus luteum did not change throughout the menstrual cycle. 4) Corpora lutea of pregnancy contained a few or no receptors which bound 125 I-LH specifically. These data suggest that LH receptor is an important factor regulating the lifespan of corpus luteum and exogenous HCG has effect on luteal insufficiency, but the effect of HCG on threatened abortion is uncertain. (author)

The effect of ovarian steroid feedback upon radioimmunoreactive luteinizing hormone releasing hormone in the hypothalamus

International Nuclear Information System (INIS)

Yanaihara, Takumi; Arai, Kiyoshi; Kanazawa, Motomi; Okinaga, Shoichi; Yanaihara, Noboru

1975-01-01

A radioimmunoassay (RIA) method for luteinizing hormone (LH) releasing hormone (RH) utilizing rabbit antiserum against synthetic (Glu 1 )-LH-RH coupled with human serum albumin at the N-terminus, is described. This assay system for LH-RH also cross-reacted with several LH-RH analogues or fragments, but not with pituitary trophic hormones. The assay was performed on the hypothalamic extracts of adult ovariectomized rats and female immature rats which had been treated with estradiol. The FSH and LH levels in the pituitary gland and serum of the same animals were determined by RIA. The radioimmunoreactive LH-RH content of the stalk median eminence markedly increased seven days after ovariectomy. The serum levels and the pituitary contents of FSH and LH of the same rats were also significantly augmented. In immature rats, the hypothalamic content of LH-RH, as measured by RIA, was significantly increased one hour after the injection of estradiol. The FSH and LH levels in the pituitary showed a significant rise after 7 hours. (auth.)

Overriding follicle selection in controlled ovarian stimulation protocols: Quality vs quantity

Directory of Open Access Journals (Sweden)

Zelinski-Wooten Mary B

2004-06-01

Full Text Available Abstract Selection of the species-specific number of follicles that will develop and ovulate during the ovarian cycle can be overridden by increasing the levels of pituitary gonadotropin hormones, FSH and LH. During controlled ovarian stimulation (COS in nonhuman primates for assisted reproductive technology (ART protocols, the method of choice (but not the only method has been the administration of exogenous gonadotropins, either of nonprimate or primate origin. Due to species-specificity of the primate LH (but not FSH receptor, COS with nonprimate (e.g., PMSG hormones can be attributed to their FSH activity. Elevated levels of FSH alone will produce large antral follicles containing oocytes capable of fertilization in vitro (IVF. However, there is evidence that LH, probably in lesser amounts, increases the rate of follicular development, reduces heterogeneity of the antral follicle pool, and improves the viability and rate of pre-implantation development of IVF-produced embryos. Since an endogenous LH surge typically does not occur during COS cycles (especially when a GnRH antagonist is added, a large dose of an LH-like hormone (i.e., hCG may be given to reinitiate meiosis and produce fertilizable oocytes. Alternate approaches using exogenous LH (or FSH, or GnRH agonist to induce an endogenous LH surge, have received lesser attention. Current protocols will routinely yield dozens of large follicles with fertilizable eggs. However, limitations include non/poor-responding animals, heterogeneity of follicles (and presumably oocytes and subsequent short luteal phases (limiting embryo transfer in COS cycles. However, the most serious limitation to further improvements and expanded use of COS protocols for ART is the lack of availability of nonhuman primate gonadotropins. Human, and even more so, nonprimate gonadotropins are antigenic in monkeys, which limits the number of COS cycles to as few as 1 (PMSG or 3 (recombinant hCG protocols in macaques

Inhibition of follicle-stimulating hormone-induced preovulatory follicles in rats treated with a nonsteroidal negative allosteric modulator of follicle-stimulating hormone receptor.

Science.gov (United States)

Dias, James A; Campo, Brice; Weaver, Barbara A; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M

2014-01-01

We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human FSHR identified an additional nonsteroidal small molecule (ADX68692). Although ADX68692 behaved like ADX61623 in inhibiting production of cAMP and progesterone, it also inhibited FSH-induced estradiol in an in vitro rat granulosa primary cell culture bioassay. When immature, noncycling female rats were injected subcutaneously or by oral dosing prior to exogenous FSH administration, it was found that ADX68692 decreased the number of oocytes recovered from the ampullae. The estrous cycles of mature female rats were disrupted by administration by oral gavage of 25 mg/kg and 10 mg/kg ADX68692. In the highest dose tested (25 mg/kg), 55% of animals cohabited with mature males had implantation sites compared to 33% in the 10 mg/kg group and 77% in the control group. A surprising finding was that a structural analog ADX68693, while effectively blocking progesterone production with similar efficacy as ADX68692, did not block estrogen production and despite better oral availability did not decrease the number of oocytes found in the ampullae even when used at 100 mg/kg. These data demonstrate that because of biased antagonism of the FSHR, nonsteroidal contraception requires that both arms of the FSHR steroidogenic pathway must be effectively blocked, particularly estrogen biosynthesis. Thus, a corollary to these findings is that it seems reasonable to propose that the estrogen-dependent diseases such as endometriosis may benefit from inhibition of FSH action at the ovary using the FSHR

The role of corifollitropin alfa in controlled ovarian stimulation for IVF in combination with GnRH antagonist

Directory of Open Access Journals (Sweden)

Seyhan A

2011-08-01

Full Text Available Ayse Seyhan, Baris AtaDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, Montreal, QC, CanadaAbstract: Corifollitropin alfa is a synthetic recombinant follicle-stimulating hormone (rFSH molecule containing a hybrid beta subunit, which provides a plasma half-life of ∼65 hours while maintaining its pharmocodynamic activity. A single injection of corifollitropin alfa can replace daily FSH injections for the first week of ovarian stimulation for in vitro fertilization. Stimulation can be continued with daily FSH injections if the need arises. To date, more than 2500 anticipated normoresponder women have participated in clinical trials with corifollitropin alfa. It is noteworthy that one-third of women did not require additional gonadotropin injections and reached human chorionic gonadotropin criterion on day 8. The optimal corifollitropin dose has been calculated to be 100 µg for women with a body weight ≤ 60 kg and 150 µg for women with a body weight >60 kg, respectively. Combination of corifollitropin with daily gonadotropin-releasing hormone antagonist injections starting on stimulation day 5 seems to yield similar or significantly higher numbers of oocytes and good quality embryos, as well as similar ongoing pregnancy rates compared with women stimulated with daily rFSH injections. Stimulation characteristics, embryology, and clinical outcomes seem consistent with repeated corifollitropin-stimulated assisted reproductive technologies cycles. Multiple pregnancy or ovarian hyperstimulation syndrome rates with corifollitropin were not increased over daily FSH regimen. The corifollitropin alfa molecule does not seem to be immunogenic and does not induce neutralizing antibody formation. Drug hypersensitivity and injection-site reactions are not increased. Incidence and nature of adverse events and serious adverse events are similar to daily FSH injections. Current trials do not

Development of the radioimmunoassay for prolactin, vasopressin and argin in invasotocin in view of reproduction phenomena in normal conditions and under the action of environmental noxious agents

International Nuclear Information System (INIS)

Simionescu, L.

1979-10-01

Radioimmunoassay procedures for testosterone, thyroglobulin, gonadotropin-inhibiting urinary substance (GIS), prolactin, follicle-stimulating hormone, luteinizing hormone (LH) and vasopressin were developed with reagents either locally produced or obtained from other sources. Studies of the effects of a pesticide, Malathion, on serum prolactin, FSH and LH levels in rats and of the effects of two herbicides, Amitrol and Atrazin, on thyroglobulin levels in human thyroid cell cultures were carried out. In the former, significant effects of Malathion on serum prolactin, FSH and LH levels, depending on dose level and mode of administration, were observed. In the latter, thyroglobulin levels in the cell cultures were proved resistant to Amitrol and Atrazin. The significance of these findings is discussed

Functional study and regional mapping of 44 hormono-regulated genes isolated from a porcine granulosa cell library

Directory of Open Access Journals (Sweden)

Hatey François

2001-01-01

Full Text Available Abstract cDNA clones from a pig granulosa cell cDNA library were isolated by differential hybridisation for follicle stimulating hormone (FSH regulation in granulosa cells in a previous study. The clones that did not match any known sequence were studied for their expression in granulosa cells (treated or not by FSH and in fresh isolated ovarian follicles mainly by comparative RT-PCR analysis. These results give functional data on genes that may be implicated in follicular growing. These ESTs have been localised on the porcine genome, using a somatic cell hybrid panel, providing new type I markers on the porcine map and information on the comparative map between humans and pigs.

Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

DEFF Research Database (Denmark)

Nyboe Andersen, Anders; Nelson, Scott M; Fauser, Bart C J M

2017-01-01

OBJECTIVE: To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. DESIGN: Randomized, mul...

DNA replication timing is maintained genome-wide in primary human myoblasts independent of D4Z4 contraction in FSH muscular dystrophy.

Directory of Open Access Journals (Sweden)

Benjamin D Pope

Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is linked to contraction of an array of tandem 3.3-kb repeats (D4Z4 at 4q35.2 from 11-100 copies to 1-10 copies. The extent to which D4Z4 contraction at 4q35.2 affects overall 4q35.2 chromatin organization remains unclear. Because DNA replication timing is highly predictive of long-range chromatin interactions, we generated genome-wide replication-timing profiles for FSHD and control myogenic precursor cells. We compared non-immortalized myoblasts from four FSHD patients and three control individuals to each other and to a variety of other human cell types. This study also represents the first genome-wide comparison of replication timing profiles in non-immortalized human cell cultures. Myoblasts from both control and FSHD individuals all shared a myoblast-specific replication profile. In contrast, male and female individuals were readily distinguished by monoallelic differences in replication timing at DXZ4 and other regions across the X chromosome affected by X inactivation. We conclude that replication timing is a robust cell-type specific feature that is unaffected by FSHD-related D4Z4 contraction.

Discrepancies between Antimullerian Hormone and Follicle Stimulating Hormone in Assisted Reproduction

Directory of Open Access Journals (Sweden)

Munawar Hussain

2013-01-01

Full Text Available Data from 107 women undergoing their first IVF/ICSI were analyzed. Relationships between antimullerian hormone (AMH and follicle stimulating hormone (FSH were analyzed after dividing patients into four groups according to AMH/FSH levels. Concordance was noted in 57% of women (both AMH/FSH either normal or abnormal while 43%of women had discordant values (AMH/FSH one hormone normal and the other abnormal. Group 1 (AMH and FSH in normal range and group 2 (normal AMH and high FSH were younger compared to group 3 (low AMH and normal FSH and group 4 (both AMH/FSH abnormal. Group 1 showing the best oocyte yield was compared to the remaining three groups. Groups 3 and 4 required higher dose of gonadotrophins for controlled ovarian hyperstimulation showing their low ovarian reserve. There was no difference in cycle cancellation, clinical pregnancy, and live birth/ongoing pregnancy rate in all groups. These tests are useful to predict ovarian response but whether AMH is a substantially better predictor is not yet established.

Systemic absorption of the sunscreens benzophenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzylidene) camphor after whole-body topical application and reproductive hormone levels in humans

DEFF Research Database (Denmark)

Janjua, Nadeem Rezaq; Mogensen, Brian; Andersson, Anna-Maria

2004-01-01

reproductive hormone levels in humans after topical application. In this 2-wk single-blinded study 32 healthy volunteers, 15 young males and 17 postmenopausal females, were assigned to daily whole-body topical application of 2 mg per cm(2) of basic cream formulation without (week 1) and with (week 2) the three...... sunscreens at 10% (wt/wt) of each. Maximum plasma concentrations were 200 ng per mL BP-3, 20 ng per mL 4-MBC, and 10 ng per mL OMC for females and 300 ng per mL BP-3, 20 ng per mL 4-MBC, and 20 ng per mL OMC for men. All three sunscreens were detectable in urine. The reproductive hormones FSH, LH were...

The correlation between LH determination in the urine (luteonosticon and HI-gonavis) and serum LH, FSH, oestradiol, progesterone testosterone and prolactin levels at midcycle

International Nuclear Information System (INIS)

Kemeter, P.; Woegerbauer, C.; Gring, H.; Salzer, H.; Friedrich, F.; Breitenecker, G.

1979-01-01

Radioimmunoassays (RIA) were carried out of serum gonadotrophins, prolactin, oestradiol, progesterone and testosterone at the time of presumed ovulation in 15 normal cycles and in 4 clomiphen-stimulated cycles of 14 women. In addition, daily measurements of LH in urine were performed using two semiquantitative methods: Luteonosticon and HI-Gonavis. Finally, the viscosity of the cervical mucus was assessed daily in order to find out the optimum time for conception. LH in serum, as well as in urine, increased significantly at midcycle and so did FSH, progesterone, testosterone, prolactin and viscosity. Lutenosticon, used in the modification of Keller and Gerber 1970 showed the first significant increase 2 days before the serum LH peak. HI-Gonavis, on the other hand, showed a significant increase only on the day of LH peak in serum. The best correlation of the 3 LH methods was found between LH in serum (RIA) and HI-Gonavis in urine. For the evaluation of the optimum time for conception in normal and clomiphen-stimulated cycles, determination of the uriany LH increase at midcycle by HI-Gonavis appears to be the most economic, both in time and expense, hormone method tested. Since only one significant increase in LH becomes apparent at midcycle by this method, the interpretation of the results is easy and additional gynaecological investigations are, thus, not absolutely necessary. (author)

Relevance of the radioimmunological determination of FSH, LH, and prolactine for the diagnosis and therapy of gynaecological-endocrinological discuses, studied in the patients of the hormone consultant ward of the gynaecological hospital of the University of Cologne, 1973 to 1975

International Nuclear Information System (INIS)

Gaschler, E.

1978-01-01

The physiology of the hypophysical gonadotrophins in women is described. The group of the patients is classified, and the normal curves for FSH, LH and HPR in the serum are shown. The author tries in the main part to bring the gonadotrophins in the various syndromes which brought the patients into the clinic, for a 'hormone consultation', in connection with other clinical findings and to compare also the individual syndromes with each other. We can see that the gonadotrophin determination can, in correct indication, be a valuable diagnostic aid which, even if used only once, is highly reliable, thanks to the accuracy of the radio immune-systems used today. (orig./AJ) [de

Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by proteoliposomes and cultured rat sertoli cells: Evidence for involvement of voltage-activated and voltage-independent calcium channels

International Nuclear Information System (INIS)

Grasso, P.; Reichert, L.E. Jr.

1989-01-01

We have previously reported incorporation into liposomes of Triton X-100-solubilized FSH receptor-G-protein complexes derived from purified bovine calf testis membranes. In the present study we have used this model system to show that FSH induces flux of 45Ca2+ into such proteoliposomes in a hormone-specific concentration-dependent manner. FSH, inactivated by boiling, had no stimulatory effect on 45Ca2+ flux, nor did isolated alpha- or beta-subunits of FSH. Addition of GTP (or its analogs 5'-guanylylimidodiphosphate and guanosine-5'-O-[3-thiotriphosphate]) or sodium fluoride (in the presence or absence of GTP or its analogs) failed to induce 45Ca2+ flux into proteoliposomes, suggesting that the uptake of 45Ca2+ was receptor, and not G-protein, related. Voltage-independent (ruthenium red and gadolinium chloride) and voltage-activated (methyoxyverapamil and nifedipine) calcium channel-blocking agents reduced FSH-stimulated 45Ca2+ flux into proteoliposomes to control levels. FSH also induced uptake of 45Ca2+ by cultured rat Sertoli cells. Ruthenium red and gadolinium chloride had no effect on basal levels of 45Ca2+ uptake or estradiol secretion by cultured rat Sertoli cells, nor did methoxyverapamil or nifedipine. All four calcium channel blockers, however, were able to reduce FSH-induced 45Ca2+ uptake to basal levels and FSH-stimulated conversion of androstenedione to estradiol by up to 50%, indicating an involvement of Ca2+ in FSH-stimulated steroidogenesis. Our results suggest that the well documented changes in intracellular calcium levels consequent to FSH binding may be due, at least in part, to an influx of calcium through FSH receptor-regulated calcium channels

Radioimmunoassay for human ACTH

Energy Technology Data Exchange (ETDEWEB)

Matsumura, S; Oyama, H; Tenku, A; Horino, M [Kawasaki Medicial School, Kurashiki, Okayama (Japan); Kobayashi, K

1977-03-01

A radioimmunoassay method for human adrenocorticotropic hormone (ACTH) is described. The antiserum was produced in a guinea pig by multiple injections of a total of 1 mg of porcine ACTH adsorbed with CM-cellulose and mixed with complete Freund's adjuvant. The antiserum used for this study at a final dilution of 1:500,000 was obtained from a guinea pig after 10 immunizations. A highly purified native ACTH (Li, ..cap alpha.. sub(h)sup(1-39) ACTH) was used as an assay standard and a tracer hormone. Separation of free and bound hormone was achieved by dextran coated charcoal. Extraction of ACTH from plasma samples was performed by Donald's method modified with silicic acid. The antibody appeared to be directed against the C-terminal portion of the hormone molecule and showed no significant reaction with other pituitary hormones (GH, TSH, LH, FSH, Hpr, Oxytocin, Arginine-and Lysine-Vasopressin). Plasma ACTH levels of 5 healthy subjects at nine o'clock averaged 32 +- 8.5 pg/ml (M +- SD). Plasma ACTH concentrations in a case of Sheehan's syndrome and of an untreated adrenogenital syndrome at nine o'clock were less than 20 and 194 pg/ml, respectively. A case of Cushing's syndrome accompanied with bilateral nodular hyperplasia of the adrenal cortex showed diminished diurnal variation and normal levels of plasma ACTH. In contrast, elevated plasma ACTH levels and lack of diurnal rhythm of ACTH secretion were observed in a suspected case of Cushing's disease.

Data on the characterization of follicle-stimulating hormone monoclonal antibodies and localization in Japanese eel pituitary

Directory of Open Access Journals (Sweden)

Dae-Jung Kim

2016-09-01

Full Text Available Monoclonal antibodies were generated against recombinant follicle-stimulating hormone (rec-FSH from Japanese eel Anguilla japonica; rec-FSH was produced in Escherichia coli and purified using Ni-NTA Sepharose column chromatography.In support of our recent publication, ''Production and characterization of monoclonal antibodies against recombinant tethered follicle-stimulating hormone from Japanese eel Anguilla japonica'' [1], it was important to characterize the specificity of eel follicle-stimulating hormone antibodies. Here, the production and ELISA system of these monoclonal antibodies are presented. The affinity-purified monoclonal antibodies specifically detected eel rec-FSH in ELISA and on western blots of rec-FSH produced from CHO cells. Immunohistochemical analysis revealed that FSH staining was specifically localized in the eel pituitary. Keywords: Japanese eel, FSH, Monoclonal Antibody

Growth differentiation factor 9 reverses activin A suppression of steroidogenic acute regulatory protein expression and progesterone production in human granulosa-lutein cells.

Science.gov (United States)

Shi, Feng-Tao; Cheung, Anthony P; Klausen, Christian; Huang, He-Feng; Leung, Peter C K

2010-10-01

We have reported that growth differentiation factor 9 (GDF9) can enhance activin A (β(A)β(A))-induced inhibin B (αβ(B)) secretion in human granulosa-lutein (hGL) cells, but its effects on steroidogenic acute regulatory protein (StAR), ovarian steroidogenic enzymes, and progesterone production are unknown. We undertook this study to further evaluate GDF9 in this regard. hGL cells from women undergoing in vitro fertilization treatment were cultured with and without small interfering RNA (siRNA) transfection targeted at inhibin α-subunit or GDF9 before treatment with GDF9, activin A, FSH, or combinations. We compared StAR, P450 side-chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase expression in hGL cells and progesterone levels in culture media after these treatments. mRNA, protein, and hormone levels were assessed with real-time RT-PCR, immunoblotting, and ELISA, respectively. Data were analyzed by ANOVA followed by Tukey's test. Activin A alone reduced basal and FSH-induced progesterone production by decreasing the expression of StAR protein, which regulates the rate-limiting step in steroidogenesis but not P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase. GDF9 attenuated these activin A effects on StAR and progesterone. After transfection of α-subunit siRNA, activin A level increased (P progesterone production were attenuated (P progesterone secretion than those observed with activin A treatment alone. GDF9 attenuates the suppressive effects of activin A on StAR expression and progesterone production by increasing the expression of inhibin B, which acts as an activin A competitor.

Efecto de gonadotropinas sobre la maduración y desarrollo embrionario de oocitos bovinos cultivados in vitro

Directory of Open Access Journals (Sweden)

Roger Salgado O

2010-04-01

Full Text Available Objetivo. Evaluar el efecto de las hormonas FSH y LH sobre las tasas de maduración, fertilización y desarrollo embrionario in vitro. Materiales y métodos. Se utilizaron 1309 oocitos de ovarios de matadero, donde el medio base fue TCM-199 suplementado (FSH y LH y se conformaron cuatro tratamientos al azar: T1: sin hormonas, T2: 50 μg/ml FSH + 150 μg/ml LH; T3: 100 μg/ml FSH + 100 μg/ml LH y T4: 150 μg/ml FSH + 50 μg/ml LH. Resultados. No se presentó efecto (p>0.05 de los tratamientos suplementados con FSH y LH sobre la tasa de maduración; por el contrario, T1 fue diferente (p0.05 cuando el medio de maduración fue suplementado con FSH y LH. Conclusiones. La adición de LH en mayor proporción con respecto a la FSH en el medio de maduración induce una mayor tasa de maduración, fecundación y desarrollo embrionario in vitro a partir de oocitos bovinos recuperados postmortem.

Photobiomodulation on Stress

Directory of Open Access Journals (Sweden)

Timon Cheng-Yi Liu

2012-01-01

Full Text Available Photobiomodulation (PBM is a nondamaged modulation of laser irradiation or monochromatic light (LI on a biosystem function. It depends on whether the function is in its function-specific homeostasis (FSH. An FSH is a negative-feedback response of a biosystem to maintain the function-specific conditions inside the biosystem so that the function is perfectly performed. A function in its FSH is called a normal function. A function far from its FSH is called a dysfunctional function. The process of a function from dysfunctional to normal is called a functional normalization. For a normal function in its FSH, there are FSH-essential subfunctions (FESs, FSH-nonessential subfunctions (FNSs, and an FES/FNS-specific homeostasis (FESH/FNSH. A FSH can resist internal/external disturbances under the threshold, but can be disrupted by an FSH-specific stress (FSS. A normal/dysfunctional FSS is called a successful/chronic stress. An FESH/FNSH-specific stress was called an extraordinary/ordinary stress. A low level LI (LLL cannot directly affect a normal function, but can modulate a chronic stress. A normal function may have a chronic ordinary stress, and an LLL may modulate the chronic ordinary stress so that it promotes the normalization of the dysfunctional FNS and then upgrades the normal function. A high level LI can modulate a normal function and may be a successful stress.

Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area.

Science.gov (United States)

Yang, Yan; Lu, Xiao Song; Li, Ding Long; Yu, Yun Jiang

2013-06-01

To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels. An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied. The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks. There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.

Directory of Open Access Journals (Sweden)

Jie Wang

Full Text Available The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH and bone mineral density (BMD in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells.We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA was used to detect serum FSH, luteinizing hormone (LH, and estradiol (E2. Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL, and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank, Trap, matrix metalloproteinase-9 (Mmp-9 and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction.1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner.The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?

Science.gov (United States)

Berkkanoglu, Murat; Ozgur, Kemal

2010-07-01

To find out the optimum maximal dosage of recombinant follicle stimulating hormone (rFSH) in microdose gonadotropin-releasing hormone analog (GnRH-a) flare cycles in poor responders. Prospective randomized study. Private infertility clinic. A total of 119 women were taken into the study. The study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration. On the third day of GnRH-a administration, 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH (group A, n = 38), or 450 IU of rFSH (group B, n = 39), or 600 IU of rFSH (group C, n = 42). Peak E(2) levels, days of stimulation with rFSH, total rFSH dosage, total number of oocytes retrieved, M2 oocytes retrieved, total number of embryos, number of embryos transferred, number of Grade-1 embryos transferred, clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer. Clinical pregnancy rates were 13.1%, 15.3%, and 16.1% for group A, group B, and group C, respectively. There were no significant differences in the age, peak serum E(2) concentration, days of stimulation with rFSH, total number of M2 oocytes retrieved, number of embryos transferred, clinical pregnancy rates, and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage. There is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles. In addition, because the duration of stimulation does not differ between the groups, the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages, and this would obviously cost less money to the patients. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

International Nuclear Information System (INIS)

Grasso, P.; Reichert, L.E. Jr.

1990-01-01

We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel

Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

Energy Technology Data Exchange (ETDEWEB)

Grasso, P.; Reichert, L.E. Jr. (Albany Medical College, NY (USA))

1990-08-01

We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.

Studies on luteinizing hormone receptors of human corpora lutea during menstrual cycle and pregnancy

Energy Technology Data Exchange (ETDEWEB)

Izumi, Yasushi (Keio Univ., Tokyo (Japan). School of Medicine)

1982-10-01

With the purpose of explicating the lifespan of human corpora lutea, using human corpora lutea of the menstrual cycle and pregnancy, binding of /sup 125/I-LH to the 20,000g cell membrane fraction was examined. 1) Specific bindings of /sup 125/I-LH, /sup 125/I-HCG were demonstrated in the 20,000g cell membrane fraction. Although LH and HCG were parallel in inhibiting /sup 125/I-LH binding, HCG was found to be more effective. FSH did not inhibit binding. 2) Binding of /sup 125/I-LH was dependent on time, temperature, /sup 125/I-LH concentration, amount of the cell membrane fraction protein and pH. The highest binding was seen at pH 6.0 while incubating for 60 min at 37/sup 0/C. 3) The number of LH receptors in human corpora lutea of the menstrual cycle increased towards midluteal phase, especially on 5th day from ovulation, and decreased towards late luteal phase. LH receptor was not found in corpus albicans. The apparent dissociation constant of each corpus luteum did not change throughout the menstrual cycle. 4) Corpora lutea of pregnancy contained a few or no receptors which bound /sup 125/I-LH specifically. These data suggest that LH receptor is an important factor regulating the lifespan of corpus luteum and exogenous HCG has effect on luteal insufficiency, but the effect of HCG on threatened abortion is uncertain.

Avaliação da aplicabilidade da técnica de maturação in vitro de oócitos humanos e posterior fertilização Evaluation of the usefulness of the in vitro maturation technique of human oocyte and subsequent fertilization

Directory of Open Access Journals (Sweden)

Maria Clara Magalhães dos Santos Amaral

2003-08-01

Full Text Available OBJETIVO: avaliar a aplicabilidade da técnica de maturação in vitro de oócitos humanos e posterior fertilização. MÉTODOS: estudo prospectivo não randomizado descritivo realizado no período de novembro de 1999 a março de 2001 no qual foram incluídas 15 pacientes com infertilidade tubária e 20 ciclos de fertilização in vitro. Todas assinaram o termo de consentimento livre e esclarecido antes de iniciar o estudo. As pacientes tinham idade entre 18 e 32 anos incompletos, obstrução tubária como causa exclusiva de infertilidade e índice de massa corporal inferior a 25 kg/m². As pacientes receberam 300 UI de hormônio folículo estimulante (FSH recombinante por via intramuscular no segundo dia do ciclo e doses adicionais de 150 UI no quarto e no sexto dia do ciclo. A coleta ovular foi realizada no sétimo dia do ciclo. Os oócitos foram colocados em meio TCM 199 acrescido de antibióticos, piruvato, FSH, gonadotrofina coriônica humana e soro (Serum Substitute Supplement - Irvine Scientific®. Após 48 h de cultivo, os oócitos que atingiram o estágio de metáfase II foram inseminados e os fertilizados foram transferidos. RESULTADOS: foram puncionados 144 folículos com a coleta de 67 oócitos imaturos (46,5%. Quarenta e três oócitos atingiram o estágio de metáfase II (64,2% e foram inseminados. Destes, 30 fertilizaram e 25 embriões foram transferidos para 10 pacientes. Houve uma gravidez com nascimento de um bebê. CONCLUSÃO: concluiu-se que a técnica de maturar oócitos humanos in vitro previamente à fertilização in vitro é técnica exeqüível, capaz de gerar gravidez.PURPOSE: to evaluate the usefulness of the in vitro maturation technique of human oocyte and subsequent fertilization. METHODS: this is a prospective nonrandomized, descriptive study, carried out during the period of November 1999 to March 2001, with 20 cycles of in vitro fertilization of 15 patients with tubal infertility. All signed the written informed

Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol.

Directory of Open Access Journals (Sweden)

Georg Griesinger

Full Text Available What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS based on the number of growing follicles ≥ 11 mm and/or estradiol (E2 levels?The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2 levels were less prognostic of OHSS than the number of follicles ≥ 11 mm.In comparison to long gonadotropin-releasing hormone (GnRH agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF, while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1-2% in a relatively young (aged 18 to 36 years IVF population treated in a GnRH-antagonist protocol.From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses.The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH in a gonadotropin-releasing hormone (GnRH-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG, and a combination of both, were determined.The optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at

In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA

DEFF Research Database (Denmark)

Nielsen, M. E.; Rasmussen, I. A.; Kristensen, S. G.

2011-01-01

significantly with the expression of AMHRII, but did not correlate with any of the hormones in the follicular fluid. These data demonstrate an intimate association between AR expression in immature granulosa cells, and the expression of FSHR in normal small human antral follicles and between the follicular......Human small antral follicles (diameter 3-9 mm) were obtained from ovaries surgically removed for fertility preservation. From the individual aspirated follicles, granulosa cells and the corresponding follicular fluid were isolated in 64 follicles, of which 55 were available for mRNA analysis (24...... and to the follicular fluid concentrations of AMH, inhibin-B, progesterone and estradiol. AR mRNA expression in granulosa cells and the follicular fluid content of androgens both showed a highly significant positive association with the expression of FSHR mRNA in granulosa cells. AR mRNA expression also correlated...

Review of the safety, efficacy, costs and patient acceptability of recombinant follicle-stimulating hormone for injection in assisting ovulation induction in infertile women

Directory of Open Access Journals (Sweden)

Marleen Nahuis

2009-11-01

Full Text Available Marleen Nahuis1,2,3, Fulco van der Veen1, Jur Oosterhuis2, Ben Willem Mol1, Peter Hompes3, Madelon van Wely11Center for Reproductive Medicine, Department of Obstetrics and Gynaecology (H4-205, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; 2Department of Obstetrics and Gynaecology, Medisch Spectrum Twente, Enschede, The Netherlands; 3Department of Obstetrics and Gynaecology, Free Medical University, Amsterdam, The NetherlandsAbstract: Anovulation is a common cause of female subfertility. Treatment of anovulation is aimed at induction of ovulation. In women with clomiphene-citrate resistant WHO group II anovulation, one of the treatment options is ovulation induction with exogenous follicle-stimulating hormone (FSH or follitropin. FSH is derived from urine or is produced as recombinant FSH. Two forms of recombinant FSH are available – follitropin alpha and follitropin beta. To evaluate the efficacy, safety, costs and acceptability of recombinant FSH, we performed a review to compare recombinant FSH with urinary-derived FSH products. Follitropin alpha, beta and urinary FSH products appeared to be equally effective in terms of pregnancy rates. Patient safety was also found to be comparable, as the incidence of side effects including multiple pregnancies was similar for all FSH products. In practice follitropin alpha and beta may be more convenient to use due to the ease of self-administration, but they are also more expensive than the urinary products.Keywords: follitropin apha, follitropin beta, urinary gonadotropins, polycystic ovary syndrome

PHOTOBIOMODULATION-MEDIATED PATHWAY DIAGNOSTICS

Directory of Open Access Journals (Sweden)

TIMON CHENG-YI LIU

2013-01-01

Full Text Available Cellular pathways are ordinarily diagnosed with pathway inhibitors, related gene regulation, or fluorescent protein markers. They are also suggested to be diagnosed with pathway activation modulation of photobiomodulation (PBM in this paper. A PBM on a biosystem function depends on whether the biosystem is in its function-specific homeostasis (FSH. An FSH, a negative feedback response for the function to be performed perfectly, is maintained by its FSH-essential subfunctions and its FSH-non-essential subfunctions (FNSs. A function in its FSH or far from its FSH is called a normal or dysfunctional function. A direct PBM may self-adaptatively modulate a dysfunctional function until it is normal so that it can be used to discover the optimum pathways for an FSH to be established. An indirect PBM may self-adaptatively modulate a dysfunctional FNS of a normal function until the FNS is normal, and the normal function is then upgraded so that it can be used to discover the redundant pathways for a normal function to be upgraded.

Efecto de la leptina en la producción de progesterona y estradiol por el ovario de rata

Directory of Open Access Journals (Sweden)

M. B. Rearte

2003-10-01

Full Text Available El desequilibrio de factores autocrinos/paracrinos en el ovario conduce a diversas enfermedades. El objetivo del presente trabajo fue evaluar la relación entre el factor de crecimiento insulínico 1 (IGF-1 y la leptina (Lp en la producción de progesterona (P y estradiol (E por el ovario de rata estimulado con hormona folículo estimulante (FSH. Para ello, se incubaron explantes ováricos con FSH, IGF-1 y Lp, evaluándose P y E en el sobrenadante por radioinmunoensayo. La FSH estimuló la producción de P y E por el ovario. El IGF-1 produjo un importante efecto sinérgico con FSH tanto en la síntesis de P como de E. La Lp no tuvo efecto sobre la acción de FSH en el aumento de P y E por el ovario, sin embargo revirtió el efecto sinérgico de IGF-1 sobre FSH tanto para P como para E. Podemos concluir que la Lp podría actuar directamente disminuyendo el efecto sinérgico de IGF-1 sobre FSH. Estos resultados podrían sugerir que niveles anormales de Lp encontrados en mujeres con síndrome de ovario poliquístico provocarían una desensibilización ovárica al IGF-1 que afectaría la producción de P y E.An alteration in the balance of autocrine/paracrine ovarian factors may lead to different diseases. The aim of the present report was to evaluate the relationship between insulin growth factor 1 (IGF-1 and leptin (Lp in the progesterone (P and estradiol (E production after ovarian rat FSH stimulation. Thus, ovarian explants were incubated with FSH, IGF-1 and Lp, and P and E were evaluated by means of specific radioimmunoassays. FSH increased ovarian P and E production. IGF-1 synergized with FSH in P as well as in ovarian E production. Lp had not shown any effect on the FSH capacity to increse P and E in the ovarian tissue; nevertheless it reverted the synergistic effect of IGF-1 on FSH for P as well as for E. These data raise the possibility that abnormal Lp levels may contribute to infertility in women with polycystic ovarian syndrome by

Cadmium, follicle-stimulating hormone, and effects on bone in women age 42-60 years, NHANES III

Energy Technology Data Exchange (ETDEWEB)

Gallagher, Carolyn M., E-mail: 2crgallagher@optonline.net [PhD Program in Population Health and Clinical Outcomes Research, Stony Brook University, Health Sciences Center L3-R071, Stony Brook, New York 11794-8338 (United States); Department of Preventive Medicine, Stony Brook University Medical Center, Stony Brook, New York (United States); Moonga, Baljit S. [Stony Brook University School of Dental Medicine, New York (United States); Kovach, John S. [Department of Preventive Medicine, Stony Brook University Medical Center, Stony Brook, New York (United States)

2010-01-15

Background: Increased body burden of environmental cadmium has been associated with greater risk of decreased bone mineral density (BMD) and osteoporosis in middle-aged and older women, and an inverse relationship has been reported between follicle-stimulating hormone (FSH) and BMD in middle-aged women; however, the relationships between cadmium and FSH are uncertain, and the associations of each with bone loss have not been analyzed in a single population. Objectives: The objective of this study was to evaluate the associations between creatinine-adjusted urinary cadmium (UCd) and FSH levels, and the associations between UCd and FSH with BMD and osteoporosis, in postmenopausal and perimenopausal women aged 42-60 years. Methods: Data were obtained from the Third National Health Examination and Nutrition Survey, 1988-1994 (NHANES III). Outcomes evaluated were serum FSH levels, femoral bone mineral density measured by dual energy X-ray absorptiometry, and osteoporosis indicated by femoral BMD cutoffs based on the international standard. Urinary cadmium levels were analyzed for association with these outcomes, and FSH levels analyzed for association with bone effects, using multiple regression. Subset analysis was conducted by a dichotomous measure of body mass index (BMI) to proxy higher and lower adipose-synthesized estrogen effects. Results: UCd was associated with increased serum FSH in perimenopausal women with high BMI (n=642; {beta}=0.45; p{<=}0.05; R{sup 2}=0.35) and low BMI (n=408; {beta}=0.61; p{<=}0.01; R{sup 2}=0.34). Among perimenopausal women with high BMI, BMD was inversely related to UCd ({beta}=-0.04; p{<=}0.05) and FSH ({beta}=-0.03; p{<=}0.05). In postmenopausal women with low BMI, an incremental increase in FSH was associated with 2.78 greater odds for osteoporosis (109 with and 706 without) (OR=2.78; 95% CI=1.43, 5.42; p{<=}0.01). Conclusion: Long-term cadmium exposure at environmental levels is associated with increased serum FSH, and both FSH

An homologous radioimmunoassay for chicken follicle-stimulating hormone: observations on the ovulatory cycle

International Nuclear Information System (INIS)

Scanes, C.G.; Godden, P.M.M.; Sharp, P.J.

1977-01-01

A highly purified FSH preparation has been used to develop a specific homologous radio-immunoassay for chicken FSH which is sufficiently sensitive and precise to measure the hormone in small samples (10-100 μl) of plasma. The assay was used to measure plasma FSH in the chicken and turkey. The FSH concentration was higher in sexually mature chickens than in juvenile birds and further elevated after castration or ovariectomy. In turkeys, it was lower in birds held on a short daily photoperiod than in birds held on a long daily photoperiod. FSH rose in sexually quiescent female turkeys after injection of synthetic L-H releasing hormone and was increased in laying hens after injection of progesterone. No major changes were observed in FSH concentration during the chicken ovulatory cycle, although there was a small increase between 15 and 14 h before ovulation. (author)

The iodination(I-125) of follicle stimulating hormone, using N-bromosuccinimide, lactoperoxidase or iodo-beads oxidators

International Nuclear Information System (INIS)

Dj., Sukiyati; S., Wayan R.; M., Gina; Ariyanto, A.

1992-01-01

The iodination (I-125) of Follicle Stimulating Hormone, using N-bromosuccinimide, lactoperoxidase or iodo-beads oxidators. FSH 125 I is one of the FSH RIA Kit reagents utilized for the determination of FSH concentration in blood serum, to study the coordination disorder of the principal hormones, i.e. hypothalamus, pituitary and gonads. To produce a good quality of FSH 125 I as a component of FSH RIA Kit, a research on the iodination(I-125) of FSH employing mild oxidant N-bromosuccinimide, lactoperoxidase, and iodo-bead has been performed. The percentage of labelling, the immunology activity and Non Specific Binding(NSB) of the labelled products were determined. The immunology activity in (%) B/T and non specific binding (%) NSB were compared with Amersham FSH RIA Kit. By the N-bromosuccinimide method, the labelling obtained was 25%, immunology activity B/T 22% (Amersham 25%) and NSB 1.3% (Amersham 1.2%). The results of labelling employing lactoperoxidase was 8.2%, immunology activity B/T 34% (Amersham 38%) and NSB 2.6% (Amersham 0.8%). Whereas labelling with Iodo-beads method produce 18%, immunology activity B/T 25% (Amersham 35%) and NSB 0.6% (Amersham 0.7%). The labelled FSH 125 I was stable with in one month stored at 4 degrees centigrade. (authors). 7 refs., 4 tabs., 1 fig

Follikel-stimulerende hormoon en interstisieelsel-stimulerende hormoon in die hipofisevoorlob van die ooi en die voorkoms van oestrus en ovulasie

NARCIS (Netherlands)

Marincowitz, G.

1964-01-01

In the Netherlands, separate activities of FSH and ICSH in the pituitary, morphological changes in ovaries and vaginal smears were examined in Texel ewes during the oestrus cycle. Both FSH and ICSH content of the pituitary decreased very sharply in late dioestrus. Immediately after ovulation, FSH

Discrepancy between molecular structure and ligand selectivity of a testicular follicle-stimulating hormone receptor of the African catfish (Clarias gariepinus)

NARCIS (Netherlands)

Bogerd, J.; Blomenröhr, M.; Andersson, E.; van der Putten, H.; Tensen, C.P.; Vischer, H F; Granneman, Joke C M; Janssen-Dommerholt, C; Goos, H.J.; Schulz, Rüdiger W

A putative FSH receptor (FSH-R) cDNA was cloned from African catfish testis. Alignment of the deduced amino acid sequence with other (putative) glycoprotein hormone receptors and analysis of the African catfish gene indicated that the cloned receptor belonged to the FSH receptor subfamily. Catfish

Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis.

Science.gov (United States)

Jayasena, Channa N; Nijher, Gurjinder M K; Chaudhri, Owais B; Murphy, Kevin G; Ranger, Amita; Lim, Adrian; Patel, Daksha; Mehta, Amrish; Todd, Catriona; Ramachandran, Radha; Salem, Victoria; Stamp, Gordon W; Donaldson, Mandy; Ghatei, Mohammad A; Bloom, Stephen R; Dhillo, Waljit S

2009-11-01

Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown. The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed. On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 +/- 3.5 IU/liter; FSH, 9.1 +/- 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 +/- 2.2 IU/liter, P < 0.05; FSH, 0.5 +/- 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed. Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.

The effects of EGF and IGF-1 on FSH-mediated in vitro maturation of domestic cat oocytes derived from follicular and luteal stages.

Science.gov (United States)

Yıldırım, Koray; Vural, M Rıfat; Küplülü, Sükrü; Ozcan, Ziya; Polat, I Mert

2014-04-01

The objective of this study was to evaluate the influence of epidermal growth factor (EGF) and insulin like growth factor-I (IGF-1) on the in vitro maturation of cat oocytes recovered from follicular and luteal stage ovaries. Oocytes from follicular (n=580) and luteal (n=209) stages were harvested and divided into four groups, which were cultured in FSH-mediated maturation medium supplemented with: (1) EGF alone (25ng/mL); (2) IGF-1 alone (100ng/mL); (3) EGF+IGF-1 (25ng/mL EGF+100ng/mL IGF-I); or (4) no growth factor (control). The proportion of follicular stage oocytes reaching the metaphase II stage was significantly higher than that of oocytes obtained at the luteal stage in both control and study groups (pIGF-1, and 78.1% in EGF+IGF-1 groups, whereas the respective values for gametes collected from luteal stage ovaries were 12.5%, 17.5%, 12.5%, and 16.9%. Additionally, the differences between the study and control groups were significant in the case of follicular stage oocytes. Finally, supplementing the maturation medium with EGF and/or IGF-1 significantly enhanced the meiotic maturation of oocytes recovered from follicular stage ovaries. The present study also demonstrated that the combination of EGF and IGF-I provides an additional or synergic effect on meiotic maturation of oocytes recovered from the follicular stage. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The Cultivation of Human Granulosa Cells

Directory of Open Access Journals (Sweden)

Lenka Brůčková

2008-01-01

Full Text Available The major functions of granulosa cells (GCs include the production of steroids, as well as a myriad of growth factors to interact with the oocyte during its development within the ovarian follicle. Also FSH stimulates GCs to convert androgens (coming from the thecal cells to estradiol by aromatase. However, after ovulation the GCs produce progesterone that may maintain a potential pregnancy. Experiments with human GCs are mainly focused on the purification of GCs from ovarian follicular fluid followed by FACS analysis or short-term cultivation. The aim of our study was to cultivate GCs for a long period, to characterize their morphology and phenotype. Moreover, we have cultivated GCs under gonadotropin stimulation in order to simulate different pathological mechanisms during folliculogenesis (e.g. ovarian hyperstimulation syndrome. GCs were harvested from women undergoing in vitro fertilization. Complex oocyte-cumulus oophorus was dissociated by hyaluronidase. The best condition for transport of GCs was optimized as short transport in follicular fluid at 37 °C. GCs expansion medium consisted of DMEM/F12, 2 % FCS, ascorbic acid, dexamethasone, L-glutamine, gentamycine, penicillin, streptomycin and growth factors (EGF, bFGF. GCs transported in follicular fluid and cultivated in 2 % FCS containing DMEM/F12 medium supplemented with follicular fluid presented increased adhesion, proliferation, viability and decreased doubling time. Cell viability was 92 % and mean cell doubling time was 52 hrs. We have optimized transport and cultivation protocols for long-term cultivation of GCs.

Concentration of activin A and follistatin in follicular fluid from human small antral follicles associated to gene expression of the corresponding granulosa cells

DEFF Research Database (Denmark)

Jeppesen, J V; Nielsen, M E; Kristensen, S G

2012-01-01

The present study correlated concentrations of activin A and follistatin in follicular fluid (FF) from human small antral follicles to FF concentrations of AMH, inhibin B, progesterone, and oestradiol and to the mRNA expression of FSH-receptor (FSHR), LH-receptor (LHR), AMH-receptor2 (AMHR2), CYP19...... activin A levels increased in follicles exceeding 10 mm in diameter. Levels of activin A and inhibin B showed a highly significant inverse association. Follistatin showed highly significant positive associations with AMH and inhibin B levels and with FSHR and AR gene expression in GC. This study revealed......a, and androgen-receptor (AR) in the corresponding granulosa cells (GC). FF from 144 follicles (3-12 mm in diameter) was included whereas mRNA expression profiles were established in GC from 66 of the 144 follicles. Levels of follistatin remained constant in relation to follicular diameter, whereas...

Appearance-based mapping and localization using feature stability histograms for mobile robot navigation

OpenAIRE

Bacca Cortés, Eval Bladimir

2012-01-01

Este trabajo propone un método de SLAM basado en apariencia cuya principal contribución es el Histograma de Estabilidad de Características (FSH). El FSH es construido por votación, si una característica es re-observada, ésta será promovida; de lo contrario su valor FSH progresivamente es reducido. El FSH es basado en el modelo de memoria humana para ocuparse de ambientes cambiantes y SLAM a largo término. Este modelo introduce conceptos como memoria a corto plazo (STM) y largo plazo (LTM), la...

Selective use of corifollitropin for controlled ovarian stimulation for IVF in patients with low anti-Müllerian hormone

DEFF Research Database (Denmark)

Nielsen, Anna Pors; Korsholm, Anne-Sofie; Lemmen, Josephine G.

2016-01-01

Corifollitropin, a long-acting follicle-stimulating hormone (FSH) analogue used for in vitro fertilization (IVF), does not allow individualization of dosage, and the ovarian response is similar to around 300 IU of daily recombinant FSH. This has raised concerns about the risk of ovarian hyperstim......Corifollitropin, a long-acting follicle-stimulating hormone (FSH) analogue used for in vitro fertilization (IVF), does not allow individualization of dosage, and the ovarian response is similar to around 300 IU of daily recombinant FSH. This has raised concerns about the risk of ovarian...

Ovotoxic effects of galactose involve attenuation of follicle-stimulating hormone bioactivity and up-regulation of granulosa cell p53 expression.

Directory of Open Access Journals (Sweden)

Sayani Banerjee

Full Text Available Clinical evidence suggests an association between galactosaemia and premature ovarian insufficiency (POI; however, the mechanism still remains unresolved. Experimental galactose toxicity in rats produces an array of ovarian dysfunction including ovarian development with deficient follicular reserve and follicular resistance to gonadotrophins that characterize the basic tenets of human POI. The present investigation explores if galactose toxicity in rats attenuates the bioactivity of gonadotrophins or interferes with their receptor competency, and accelerates the rate of follicular atresia. Pregnant rats were fed isocaloric food-pellets supplemented with or without 35% D-galactose from day-3 of gestation and continuing through weaning of the litters. The 35-day old female litters were autopsied. Serum galactose-binding capacity, galactosyltransferase (GalTase activity, and bioactivity of FSH and LH together with their receptor competency were assessed. Ovarian follicular atresia was evaluated in situ by TUNEL. The in vitro effects of galactose were studied in isolated whole follicles in respect of generation of reactive oxygen species (ROS and expression of caspase 3, and in isolated granulosa cells in respect of mitochondrial membrane potential, expression of p53, and apoptosis. The rats prenatally exposed to galactose exhibited significantly decreased serum GalTase activity and greater degree of galactose-incorporation capacity of sera proteins. LH biopotency and LH-FSH receptor competency were comparable between the control and study population, but the latter group showed significantly attenuated FSH bioactivity and increased rate of follicular atresia. In culture, galactose increased follicular generation of ROS and expression of caspase 3. In isolated granulosa cells, galactose disrupted mitochondrial membrane potential, stimulated p53 expression, and induced apoptosis in vitro; however co-treatment with either FSH or estradiol

Mapping the follicle-stimulating hormone-induced signalling networks

Directory of Open Access Journals (Sweden)

Pauline eGloaguen

2011-10-01

Full Text Available Follicle-stimulating hormone (FSH is a central regulator of male and female reproductive function. Over the last decade, there has been a growing perception of the complexity associated with FSH-induced cellular signalling. It is now clear that the canonical Gs/cAMP/PKA pathway is not the sole mechanism that must be considered in FSH biological actions. In parallel, consistent with the emerging concept of biased agonism, several examples of ligand-mediated selective signalling pathway activation by gonadotropin receptors have been reported. In this context, it is important to gain an integrative view of the signalling pathways induced by FSH and how they interconnect to form a network. In this review, we propose a first attempt at building topological maps of various pathways known to be involved in the FSH-induced signalling network. We discuss the multiple facets of FSH-induced signalling and how they converge to the hormone integrated biological response. Despite of their incompleteness, these maps of the FSH-induced signalling network represent a first step towards gaining a system-level comprehension of this hormone’s actions, which may ultimately facilitate the discovery of novel regulatory processes and therapeutic strategies for infertilities and non-steroidal contraception.

Reconsidering a lower level of follicle-stimulating hormone as abnormal in sub-fertile males of pakistan

International Nuclear Information System (INIS)

Arif, S.; Khan, A.

2017-01-01

To assess the association between Follicle-Stimulating Hormone (FSH) and semen parameters in order to evaluate whether the current laboratory reference for abnormal FSH levels should be readjusted. Study Design: Observational, cross-sectional study. Place and Duration of Study: Infertility Clinic of Gynecology Unit 1, Civil Hospital, Karachi, from May 2015 to April 2016. Methodology:The study included 100 sub-fertile males inducted from the clinic. Those above 45 years of age, with hypo gonadotrophic hypogonadism, and those on anabolic steroids were excluded. After history and examination, semen parameters and FSH levels were tested. Abnormal semen values were based on WHO 1999 criteria. Data was analyzed by SPSS 17 and mean, frequencies and percentages were calculated. Chi-square test was applied to check association between variables. Results: The FSH levels had a significant association with abnormal semen sperm concentration, motility and morphology but not with semen volume (p=0.246). The mean FSH level was 5.8 ±1.80 IU/L with two-thirds of individuals having value >4.5 IU/L. Frequency of semen abnormalities increased as the level of FSH increased. Conclusion: There is significantly an increased possibility of abnormal semen characteristics at FSH levels >4.5, so the current reference level should be lowered down and adjusted again. (author)

Follicle-stimulating hormone to substitute equine chorionic gonadotropin in the synchronization of ovulation in Santa Inês ewes

Directory of Open Access Journals (Sweden)

Bianor Matias Cardoso Neto

2012-03-01

Full Text Available The substitution of equine chorionic gonadotropin (eCG by follicle-stimulating hormone (FSH in protocols for synchronization of ovulation in Santa Inês ewes was assessed. Ten females were submitted to the insertion of intravaginal sponges containing 60 mg medroxyprogesterone acetate for 10 days; after this period sponges were withdrawn and the animals were randomly divided into two groups. Group 1 (n = 5: intramuscular injection of 0.5 mL d-cloprostenol and 300 UI eCG; Group 2 (n = 5: intramuscular injection of 0.5 mL d-cloprostenol and 20 mg FSH. Interval between sponge withdrawal and estrus beginning was 27.7 h and 35.9 h for eCG and FSH, respectively. Interval between sponge withdrawal and the end of estrus was 55.8 h for eCG treatment and 55.6 h for FSH treatment. Estrus length was 29.3 h and 19.6 h, for eCG and FSH treatments, respectively. The biggest follicle and the second in size measured 0.74 cm and 0.54 cm for eCG treatment, whereas for the FSH treatment they measured 0.73 and 0.50 cm. The interval between the beginning of estrus and ovulation was similar within all groups: 21.0 h for eCG treated ewes and 25.2 h for the ones treated with FSH. Ewes treated with eCG presented an interval of 47.5 h between sponge withdrawal and ovulation, while the ones treated with FSH presented a 61.1 h interval. Ovulation occurred 8.3 h before the end of estrus in the eCG group. On the other hand, ewes treated with FSH ovulated 5.5 h after the end of estrus. Estrus and ovulation were efficiently synchronized in Santa Inês ewes by using long-term progestogen protocol associated to the administration of 20 mg FSH, along with Prostaglandin F2α (PGF2α at the moment of sponge withdrawal, thus substituting the use of eCG.

Follicle stimulating hormone alleviates radiation-induced degeneration of mouse ovarian follicles

Energy Technology Data Exchange (ETDEWEB)

Lee, C.J. [Hanyang Univ., Seoul (Korea, Republic of); Kim, J.K.; Chun, K.J.

2000-05-01

The present study was performed to analyze the influences of (FSH) follicle stimulating hormone and {gamma}-radiation on the morphological changes of ovarian follicles and serum concentrations of testosterone, and estradiol-17{beta} in prepubertal mice. Female mice (ICR strain, three weeks old) were irradiated with 8.33 Gy of {gamma}-ray and followed by a 5 IU i.p.-injection of FSH to know the effect of FSH on the ovarian follicles. Left ovaries were collected at 0 h, 1 d, and 2 d after irradiation or saline/ FSH injection. Another group was received 5 IU of FSH 2 hours before irradiation to analyze the changes of ovarian steroidogenic abilities. By the morphometrical analysis, the number of normal or atretic follicles was counted and the ratio of normal to atretic follicle numbers was calculated. The percentage of atretic follicles was significantly reduced by the treatment of FSH. In the case of the FSH-injected group, the cellular debris caused by radiation was engulfed by the immune cells and the neighboring granulosa cells within the follicles. In concurrence with the morphometric analysis, the changes of the serum concentrations (pg/ml) of testosterone (T) and estradiol (E{sub 2}) were determined by radioimmunoassays. The concentration of T was 336.8{+-}61.3 in the control mice. One day after irradiation, the concentration went up to 484.8{+-}80.0 in the irradiated group, and down to 243.5{+-}80.7 in the FSH-treated one. The concentration of E{sub 2} was 174.9{+-}15.0 in the control group. One day after irradiation, however, the concentration was decreased to 94.8{+-}19.8, and 155.9{+-}8.7 in the irradiated and FSH-treated group, respectively. The alleviation of the follicular degeneration by the treatment of FSH is closely related to the elimination of the cellular debris and to the activities of the steroidogenic enzymes. (Author)

Auto immunity in the Ovarian Resistance Syndrome: research and methodology development

International Nuclear Information System (INIS)

Oliver, P.; Balter, H.; Robles, A.

1998-01-01

The project evaluates, it selects it develops, it optimizes and been worth, analytic methods for the detection and quantification of antibodies antireceptor of FSH, decisive of precocious ovarian flaw for insensibility gonadal: Syndrome of Ovarian Resistance (SRO). The study method involves the competitive inhibition of the union marked FSH with Iodine-125 of membrane receiver. The investigations include the following components of the analysis system: to) membrane Receivers, b) Radiotracers, c) negative and positive control Serums, d) Buffers. The constants of likeness and numbers of receivers are evaluated in the material biological employee by means of graphics of Scatchard. Ace for the control of quality, the study of the maximum capacity of union was selected of the ligature to the receiver, like one of the parameters that bigger information toasts on the performance of the same one. The clinical validation was made by means of the use of isolated immuno-globulines starting from the serum of healthy donors considered as negative power stations and of women with SRO confirmed by studies made in the exterior considered as central positive. All this, provides the development of a sensitive and specific reliable qualitative method for the determination of antibodies antireceptor of FSH of immediate application in the area of the human health in our means [es

Hormonal control of spermatogenesis in men: therapeutic aspects in hypogonadotropic hypogonadism.

Science.gov (United States)

Pitteloud, Nelly; Dwyer, Andrew

2014-05-01

During the first two trimesters of intrauterine life, fetal sex steroid production is driven by maternal human chorionic gonadotropin (hCG). The HPG axis is activated around the third trimester and remains active for the first 6-months of neonatal life. This so-called mini-puberty is a developmental window that has profound effects on future potential for fertility. In early puberty, GnRH secretion is reactivated first at night and then night and day. Pulsatile GnRH stimulates both LH and FSH, which induce maturation of the seminiferous tubules and Leydig cells. Congenital hypogonadotropic hypogonadism (CHH) results from GnRH deficiency. Men with CHH lack the mini-pubertal and pubertal periods of Sertoli Cell proliferation and thus present with prepubertal testes (Fertility outcomes with each of these regimens are highly variable. Recently, a randomized, open label treatment study (n=13) addressed the question of whether a sequential treatment with FSH alone prior to LH and FSH (via GnRH pump) could enhance fertility outcomes. All men receiving the sequential treatment developed sperm in the ejaculate, whereas 2/6 men in the other group remained azoospermic. A large, multicenter clinical trial is needed to definitively prove the optimal treatment approach for severe CHH. Copyright © 2014. Published by Elsevier Masson SAS.

The Effect of Four Different Gonadotropin Protocols on Oocyte and Embryo Quality and Pregnancy Outcomes in IVF/ICSI Cycles; A Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Mohammad Ebrahim Parsanezhad

2017-01-01

Full Text Available Background: Despite the large number of papers published on the efficiency of different exogenous gonadotropins, no confirmed protocol exists. Therefore, the aim of the present study was to compare the efficacy of 4 exogenous gonadotropins in IVF/ICSI cycles. Methods: This study, performed from January 2014 to May 2014, recruited 160 women referred to Ghadir Mother and Child Hospital and Dena Hospital, Shiraz, Iran. The patients underwent standard downregulation and were randomly divided into 4 groups of A, B, C, and D and were administered hMG, hFSH, rFSH, and combined sequential hFSH/rFSH, respectively. Then, the duration of stimulation, number of oocytes and embryos as well as their quality, implantation rate, biochemical and clinical pregnancy rate, and live birth rate in each group were evaluated. Results: Group D patients required significantly fewer ampoules of FSH than did the women in groups A, B, and C (P=0.004. The duration of stimulation was significantly longer in group C than in groups A and D (P=0.030. The serum estradiol level was significantly higher in group D than in groups B and C (P=0.005. A significantly higher number of large-sized follicles was observed in group D than in group B (P=0.036. Conclusion: Our data revealed no statistically significant differences in the mean oocyte number, embryo quality, clinical pregnancy rate, or live birth rate between the hMG, hFSH, rFSH, and sequential hFSH/rFSH protocols. However, several differences in the duration of stimulation, serum estradiol levels, and number of large-sized follicles were detected between the groups. Trial Registration Number: IRCT201408116541N7

Modulation of cultured porcine granulosa cell responsiveness to follicle stimulating hormone and epidermal growth factor

Energy Technology Data Exchange (ETDEWEB)

Buck, P.A.

1986-01-01

Ovarian follicular development is dependent upon the coordinated growth and differentiation of the granulosa cells which line the follicle. Follicle stimulating hormone (FSH) induces granulosa cell differentiation both in vivo and in vitro. Epidermal growth factor (EGF) stimulates granulosa cell proliferation in vitro. The interaction of these two effectors upon selected parameters of growth and differentiation was examined in monolayer cultures of porcine granulose cells. Analysis of the EGF receptor by /sup 125/I-EGF binding revealed that the receptor was of high affinity with an apparent dissociation constant of 4-6 x 10/sup -10/ M. The average number of receptors per cell varied with the state of differentiation both in vivo and in vitro; highly differentiated cells bound two-fold less /sup 125/I-EGF and this effect was at least partially induced by FSH in vitro. EGF receptor function was examined by assessing EGF effects on cell number and /sup 3/H-thymidine incorporation. EGF stimulated thymidine incorporation in both serum-free and serum-supplemented culture, but only in serum-supplemented conditions was cell number increased. EGF receptor function was inversely related to the state of differentiation and was attenuated by FSH. The FSH receptor was examined by /sup 125/I-FSH binding. EGF increased FSH receptor number, and lowered the affinity of the receptor. The function of these receptors was assessed by /sup 125/I-hCG binding and progesterone radioimmunoassay. If EGF was present continuously in the cultures. FSH receptor function was attenuated regardless of FSH receptor number. A preliminary effort to examine the mechanism of this interaction was performed by analyzing hormonally controlled protein synthesis with /sup 35/S-methionine labeling, SDS polyacrylamide gel electrophoresis and fluorography. FSH promoted the expression of a 27,000 dalton protein. This effect was attenuated by EGF.

Clinical study of serum hormone levels in male sexual insufficiency by radioimmunoassay

International Nuclear Information System (INIS)

Yang Yongqing; Fang Zhenyang; Qian Runqing

1992-01-01

The study of serum-hormone levels by radioimmunoassay in 525 patients with male sexual insufficiency is described. The results showed that testosterone (T) level in 50 normal cases were 501.0 +- 108.0 ng/dl, but serum FSh, LH and PRL were 13.6 +- 8.2 m IU/ml, 7.8 +- 5.5 mIU/ml, 15.97 +-5.43 ng/ml respectively. 15 cases of genotype with Klinefelter's syndrome are all 47, XXY. No significant difference were noted in the serum T levels between Klinefelter's syndrome and normal controls, but the serum FSH was significantly increased (58.78 +- 22.07 mIU/ml). If the level of T falls and FSH and LH rise the sterility mostly results from testicle diseases. If T, FSH and LH are all normal, in most cases the sterility results from obstructed aspermia. If the PRL rises and T, FSH and LH are all in lower values it would be possibly hypogonadotrophinmia. If T is low, FSH and LH rises, the under development of testes should be considered

Polycystic ovarian disease.

Science.gov (United States)

Raj, S G; Talbert, L M

1984-01-01

Polycystic ovarian disease (PCOD) was first described as a single disease by Stein and Leventhal in 1935, but now has been separated into several distinct entities, comprising a symptom complex. The most frequent presenting symptoms associated with PCOD are obesity, hirsutism, amenorrhea or anovulation, dysfunctional uterine bleeding, irregular menses, and infertility. The common finding of hirsutism in PCOD patients is a reflection of the hyperandrogenism resulting from elevation of all the androgens, including testosterone, androstenediol, dehydroepiandrostrone sulfate (DHEA-S), and androstenedione. Some patients with all the clinical features of PCOD can be shown, through appropriate testing, to have an attenuated form of classic congenital adrenal hyperplasia (CAH). Serum follicle stimulating hormone (FSH) levels are usually low or in the normal range, and serum luteinizing hormone (LH) levels are usually elevated in patients with PCOD, resulting in an altered LH/FSH ratio. Treatment for PCOD must be based on the needs and desires of the individual patient, and on the pathophysiology of the patient's particular abnormalities. When pregnancy is desired, ovulation induction with clomiphene is indicated. Clomiphene is a weak estrogen that induces a transient rise in serum LH and FSH, followed by a gonadotropic pattern similar to normal cycles. A 72% ovulation rate and a 41.8% conception rate have been reported after treatment with clomiphene. In patients who do not respond to clomiphene, or clomiphene with added human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG) can be used to induce ovulation, but the patient should be closely monitored for multiple ovulation, multiple pregnancy, or hyperstimulation syndrome. For patients not interested in conception, regular menstrual cyclicity can be restored and hyperandrogenism reduced with oral contraceptives (OCs).

Exposure to organophosphate pesticides and male hormone profile in floriculturist of the state of Morelos, Mexico.

Science.gov (United States)

Blanco-Muñoz, Julia; Morales, Magally Mayanin; Lacasaña, Marina; Aguilar-Garduño, Clemente; Bassol, Susana; Cebrián, Mariano E

2010-07-01

Studies on experimental animals have found that organophosphate (OP) pesticides may act as endocrine disruptors; however, their effects on the human hormonal profile have not yet been adequately characterized. We evaluate the association between exposure to OP pesticides, measured through dialkyl phosphate (DAP) metabolites urinary levels, and the male hormone profile. A cross-sectional study was performed in 104 floriculturists of Morelos, Mexico. A structured questionnaire was applied to get information on sociodemographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, and work history. DAP metabolites [dimethylphosphate (DMP), dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate] were determined using gas-liquid chromatography. Serum levels of FSH, LH, prolactin, testosterone, inhibin B and estradiol were determined using enzyme-linked immunosorbent assay. Multiple linear regression was used to study the association between DAP metabolite levels and male hormonal profile. Data were adjusted by p,p'-dichlorodiphenyldichloroethene serum levels and other potential confounders. There was a negative association between inhibin B and urinary levels of DMP, DEP, DETP and total DAP metabolites. DEP levels were negatively associated with serum FSH concentrations, but marginally and positively associated with those of testosterone. DETP was marginally associated with lower LH serum levels. There were no other significant associations among OP metabolites and serum hormone levels. Inhibin B and FSH vary according to levels of DAP metabolites in men occupationally exposed to OP pesticides. These results suggest that OP pesticides could act as endocrine disruptors in humans; however, most hormonal values fell within the wide normal range and associations were small. There is, therefore, a need for further investigation to elucidate their biological and clinical

Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells

International Nuclear Information System (INIS)

Gao, Hui; Lin, Lu; Haq, Ihtesham Ul; Zeng, Shen-ming

2016-01-01

The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. - Highlights: • FSH inhibits the activation of NF-κB in porcine primary granulosa cells. • Inhibition of NF-κB by FSH promotes autophagy via JNK signaling in granulosa cells. • Increased autophagy contributes to progesterone production in granulosa cells. • This is the first report against beclin1 regulation in porcine granulosa cells.

Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells

Energy Technology Data Exchange (ETDEWEB)

Gao, Hui; Lin, Lu; Haq, Ihtesham Ul; Zeng, Shen-ming, E-mail: zengshenming@gmail.com

2016-04-22

The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. - Highlights: • FSH inhibits the activation of NF-κB in porcine primary granulosa cells. • Inhibition of NF-κB by FSH promotes autophagy via JNK signaling in granulosa cells. • Increased autophagy contributes to progesterone production in granulosa cells. • This is the first report against beclin1 regulation in porcine granulosa cells.

Serum androgen binding protein and follicle stimulating hormone as indices of Sertoli cell function in the irradiated testis

International Nuclear Information System (INIS)

Delic, J.I.; Hendry, J.H.; Shalet, S.M.; Morris, I.D.

1986-01-01

The present study presents evidence of radiation-induced Sertoli cell damage in both the pubertal and adult rat. The indirect measurement of Sertoli cell function, serum follicle stimulating hormone (FSH), in general mirrored the changes seen in androgen binding protein (ABP), again indicating Sertoli cell dysfunction. Although FSH remained elevated in adult rats after 5 Gy and above and in pubertal rats after 10 and 20 Gy, the elevation was not as great as that observed in castrates. This suggests that FSH secretion was still inhibited by some factor. As ABP was reduced to near 'background' (castrate) levels after these high doses, suggesting Sertoli cell dysfunction, this may indicate that serum ABP levels may not adequately reflect all Sertoli cell functions. Alternatively FSH may have been inhibited by by Leydig cell androgens, which have been demonstrated to modulate, in part, FSH secretion. Although the Leydig cells were damaged, androgen secretion was not entirely reduced during the study. In general, FSH was elevated when severe damage to spermatogenesis was noted. Whether the changes were related to the absence of a specific spermatogenic cell type could not be determined. (UK)

Follicle stimulating hormone increases spermatogonial stem cell colonization during in vitro co-culture.

Science.gov (United States)

Narenji Sani, Reza; Tajik, Parviz; Yousefi, Mohammad Hassan; Movahedin, Mansoureh; Qasemi-Panahi, Babak; Shafiei, Shiva; Ahmadi Hamedani, Mahmood

2013-01-01

The complex process of spermatogenesis is regulated by various factors. Studies on spermatogonial stem cells (SCCs) have provided very important tool to improve herd genetic and different field. 0.2 to 0.3 percent of total cells of seminiferous tubules is consist of spermatogonial stem cells. To investigate and biomanipulation of these cells, proliferation and viability rate of cells should be increased in vitro, at first. Follicle stimulating hormone (FSH) has been suggested to play a determinant role in the survival of germ cells in addition to increasing spermatogonial proliferation. In this study, the in vitro effects of FSH on spermatogonial cell colony formation were investigated. Sertoli and spermatogonial cells were isolated from 3-5 months old calves. The identity of the Sertoli cells and spermatogonial stem cells were confirmed through immunocytochemistry and colony morphology, respectively. Co-cultured Sertoli and spermatogonial cells were treated with FSH in different dose of 10, 20 and 40 IU mL(-1) FSH, before colony assay. Results indicated that, FSH increased in vitro colonization of spermatogonial cells in comparison with control group. In conclusion, using FSH provided proper bovine spermatogonial stem cell culture medium for in vitro study of these cells.

Regulation of the phosphoinositide pathway in cultured Sertoli cells from immature rats: effects of follicle-stimulating hormone and fluoride

International Nuclear Information System (INIS)

Quirk, S.M.; Reichert, L.E. Jr.

1988-01-01

Many hormones elicit effects on target cells by stimulating the enzyme phospholipase-C, which catalyzes the hydrolysis of phosphoinositides to the intracellular second messengers diacylglycerol and inositol phosphates. The present study examined the roles of FSH and guanine nucleotide-binding proteins (G-proteins) in regulating the hydrolysis of phosphoinositides in Sertoli cells. Sertoli cell cultures prepared from 16- to 18-day-old rats were incubated for 24 h with myo-[2-3H] inositol to label endogenous phospholipids. Treatment of cells from 0.5-20 min with preparations of ovine FSH ranging in potency from 1-60 times that of NIH FSH S1 did not affect accumulation of inositol phosphates. Levels of total [3H]inositol phosphates [[3H]inositol mono-, di-, and triphosphates (IP, IP2, and IP3)] in FSH-treated cultures was 75-120% the levels in control cultures over the various time intervals studied. Addition of testosterone and the combination of testosterone plus retinoic acid, agents that have been shown to potentiate effects of FSH in other systems, did not affect accumulation of inositol phosphates in response to FSH. In contrast to the lack of effect on accumulation of inositol phosphates, FSH stimulated 4- to 11-fold increases in estradiol secretion over 24 h of culture, indicating that Sertoli cells were viable and responsive to FSH. AIF4- has been shown to activate G-proteins involved in regulation of adenylate cyclase activity. In the present study, AIF4- induced 4- to 5-fold increases in IP, IP2, and IP3 in experiments wherein FSH had no effect. Pretreatment of Sertoli cells with pertussis toxin (100 and 1000 ng/ml) for 24 h inhibited fluoride-induced generation of IP, IP2, and IP3 by 24-51%. Similar treatment with cholera toxin had no effect on basal or fluoride-induced generation of IP2 or IP3, but increased fluoride-induced generation of IP by 20-34%

Labelling and standardizing some pituitary hormones for radioimmunoassay

International Nuclear Information System (INIS)

Kim, Y.S.

1976-11-01

Optimum conditions for efficient 125 I labelling of human follicle stimulating hormone (FSH) and human chorionic gonadotropin (HCG) using chloramine-T have been established for radioimmunoassay (RIA). The amount of the hormone, chloramine-T, 125 I, and the reaction time were, respetively, controlled evaluating the yield and the bindability of the labelled hormone to its antibody. To measure the bindability, the labelled hormone was incubated together with its antibody for a definite temperature. In the separation of the free hormone (F) from the antibody bound (B), a double antibody technique was applied comparing with the chromatoelectrophoresis. For the efficient separation of the labelled hormone, two methods of separation such as gel filtration and gel electrophoresis were compared in the sensitivity and in the immunological activity points of view. Experiments for the production of HCG antibody were also conducted. The produced antisera were tested in two ways; i.e., the incubation test with the labelled hormone, and the Ouchterlony test. Using the produced anti-HCG serum and the purchased anti-FSH serum, standard dose-response curves were plotted correlating with the international standard preparation of the hormones

Luteinizing hormone-follicle stimulating hormone ratio as biological predictor of post-partum depression.

Science.gov (United States)

Ramachandran Pillai, R; Sharon, Leena; Premkumar, Nancy R; Kattimani, Shivanand; Sagili, Haritha; Rajendiran, Soundravally

2017-01-01

Post-partum depression (PPD) is the common adverse outcome of child bearing which affects the wellbeing of both mother and newborn and has long-term effects. Hence, reliable potential biological tests for early detection of PPD are essential. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were associated with depressive disorders and the present study estimated the levels of serum FSH, LH in postpartum depression and explored them as predictive biomarkers in the development of PPD. In this nested case control study done at a tertiary care hospital in South India, 450 postpartum women were screened at 6th week post-delivery for PPD. Socio-demographic and clinical data were recorded and depressive symptoms were assessed using Edinburgh Postnatal Depression Scale (EPDS). Out of 450 subjects screened, 100 women with depressive symptoms were categorized as cases and 100 controls were selected from the remaining subjects matching for age and BMI with cases. Serum levels of FSH and LH were measured using direct competitive immunoassay by chemiluminescene technology. Serum LH/FSH ratio was found to be significantly (p=0.02) low in PPD women when compared to normal postpartum subjects. We also found a significant negative correlation between LH/FSH ratio and EPDS scores. Based on the receiver operating characteristic curve, the optimal cut-off value for serum of LH/FSH levels in predicting postpartum depression was estimated to be 0.22mlU/mL with an AUC of 0.598 (95%CI, 0.291-0.859). Our study demonstrated that low LH/FSH ratio after delivery was associated with increased risk for the development of PPD. Low LH/FSH ratio at six-week post delivery can be used as a robust biochemical predictor of post-partum depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical pregnancy in a woman with idiopathic hypogonadotropic hypogonadism and low AMH: utility of ovarian reserve markers in IHH.

Science.gov (United States)

Chan, Crystal; Liu, Kimberly

2014-10-01

Serum anti-mullerian hormone (AMH) has been proposed as a useful marker of ovarian reserve that is cycle-independent and predictive of outcome in assisted reproduction cycles. However, there is evidence that AMH production is gonadotropin-dependent, and that under the influence of FSH, growing follicles contribute to circulating AMH levels. Therefore, AMH testing may not be universally reflective of the primordial follicle pool in certain conditions. We demonstrate that in patients with idiopathic hypogonadotropic hypogonadism (IHH) and deficient gonadotropin production, AMH and antral follicle count (AFC) may not be reliable markers of ovarian reserve. Case report. Fertility clinic at a tertiary academic hospital. A 30-year-old nulligravid patient with IHH who presented for fertility treatment with low FSH (0.3 IU/L), LH (0.1 IU/L), estradiol (77 pmol/L) and AMH levels (0.65 pmol/L), and an unmeasurable AFC. A three-month course of priming with oral micronized 17β-estradiol, followed by daily injections of human menopausal gonadotropins (hMG). AMH level and follicular development. After 60 days of stimulation with hMG, the patient's AMH level increased to a peak of 1.27 pmol/L. After 102 days of stimulation, her estradiol level rose to 480 pmol/L and a 19 mm dominant follicle was detected. The patient successfully conceived with intrauterine insemination. Ovarian reserve testing in patients with IHH can be challenging due to the contracted appearance of the ovaries and deficient FSH production. In these patients, AMH levels may underestimate ovarian reserve due to the lack of FSH-dependent growing follicles. When treated with a long course of hMG, these patients may exhibit increased AMH levels and demonstrate adequate follicular development.

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

Science.gov (United States)

Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

1992-10-01

To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Auto immunity in the Ovarian Resistance Syndrome: research and methodology development; Autoinmunidad en el Sindrome de Resistencia Ovarica: investigacion y desarrollo de metodologia

Energy Technology Data Exchange (ETDEWEB)

Oliver, P; Balter, H; Robles, A

1998-07-01

The project evaluates, it selects it develops, it optimizes and been worth, analytic methods for the detection and quantification of antibodies antireceptor of FSH, decisive of precocious ovarian flaw for insensibility gonadal: Syndrome of Ovarian Resistance (SRO). The study method involves the competitive inhibition of the union marked FSH with Iodine-125 of membrane receiver. The investigations include the following components of the analysis system: to) membrane Receivers, b) Radiotracers, c) negative and positive control Serums, d) Buffers. The constants of likeness and numbers of receivers are evaluated in the material biological employee by means of graphics of Scatchard. Ace for the control of quality, the study of the maximum capacity of union was selected of the ligature to the receiver, like one of the parameters that bigger information toasts on the performance of the same one. The clinical validation was made by means of the use of isolated immuno-globulines starting from the serum of healthy donors considered as negative power stations and of women with SRO confirmed by studies made in the exterior considered as central positive. All this, provides the development of a sensitive and specific reliable qualitative method for the determination of antibodies antireceptor of FSH of immediate application in the area of the human health in our means. [Spanish] El proyecto evalua, selecciona, desarrolla, optimiza y valida, metodos analiticos para la deteccion y cuantificacion de anticuerpos antireceptor de FSH, determinantes de falla ovarica precoz por insensibilidad gonadal: Sindrome de Resistencia Ovarica (SRO). El metodo de estudio involucra la inhibicion competitiva de la union hFSH marcada con Iodo-125 de receptor de membrana. Las investigaciones incluyen los siguientes componentes del sistema de analisis: a) Receptores de membrana, b) Radiotrazadores, c) Sueros de control negativos y positivos, d) Buffers. Se evaluan las constantes de afinidad y numeros

The Correlations of Anti-Mullerian Hormone, Follicle-Stimulating Hormone and Antral Follicle Count in Different Age Groups of Infertile Women

Directory of Open Access Journals (Sweden)

Ludmila Barbakadze

2015-02-01

Full Text Available Background: The objective of our study was to identify the correlations between the tests currently used in ovarian reserve assessment: anti-Mullerian hormone (AMH, follicle stimulating hormone (FSH and antral follicle count (AFC and to distinguish the most reliable markers for ovarian reserve in order to select an adequate strategy for the initial stages of infertility treatment. Materials and Methods: In this prospective study, 112 infertile women were assessed. Subjects were divided into three age groups: group I <35 years (n=39, group II 35-40 years (n=31, and group III 41-46 years (n=42. AMH, FSH and AFC were determined on days 2-3 of the patients’ menstrual cycles. Results: There was a significantly elevated negative correlation between age and AMH level (rs =-0.67, p<0.0001 and AFC (rs =-0.55, p<0.0001. We observed a significantly positive correlation between age and FSH (rs =0.38, p<0.0001. AMH negatively correlated with FSH (rs =-0.48, p<0.0001 and positively with AFC (r=- 0.71, p=0.0001. There was a moderate negative relation between FSH and AFC (r=-0.41, p=0.0001 and moderate positive relation between age and FSH (rs =0.38, p<0.0001. The correlation analysis performed in separate groups showed that AMH and AFC showed a statistically significant positive correlation for group I (r=0.57, p<0.0001, group II (r=0.69, p<0.0001 and group III (r=0.47, p<0.002. A statistically significant correlation between FSH and AMH was detected only in groups I (r=-0.41, p<0.02 and II (r=-0.55, p<0.0001. A statistically significant correlation existed between FSH and AFC only in group III (r=-0.42, p<0.006, as well as between age and AFC only in group I (r=-0.35, p<0.03. Conclusion: Currently, AMH should be considered as the more reliable of the ovarian reserve assessments tests compared to FSH. There is a strong positive correlation between serum AMH level and AFC. The use of AMH combined with AFC may improve ovarian reserve evaluation.

Influence of commercially available follicle stimulating hormone on the in vitro maturation of bovine oocytes

Directory of Open Access Journals (Sweden)

Maria Valéria de Oliveira Santos

2017-06-01

Full Text Available The work aimed (Experiment I to compare commercial representations of porcine follicle stimulating hormone (FSH, Pluset® vs. Folltropin® in concentration (10 ?g/mL and time (24 h standard (more used in protocols of in vitro maturation, IVM; (Experiment II to evaluate the best incubation time (6 h vs. 16 h vs. 24 h and, (Experiment III analyze varying concentrations (1.0 ?g/mL vs. 2.5 ?g/mL vs. 10.0 ?g/mL of representations of FSH on the IVM of bovine oocytes. Thus, oocytes were recovered and submitted to IVM under appropriate conditions. After the IVM, oocytes were evaluated for expansion of cumulus cells (CCs, presence of the first polar body (1PB and metaphase plate (MII. All the data were analyzed by the Fisher exact test (P 0.05 was observed in maturation rates of the oocytes incubated with FSH Pluset® or Folltropin®, assessed by expansion of CCs (97.6% vs. 94.3%, presence of 1PB (76.6% vs. 69.4% and MII (70.0% vs. 68.6%. In Experiment II, when the incubation time with FSH was evaluated, both Pluset® as Folltropin® showed lower rate of expansion of CCs when they were present only in the first 6 h of IVM. As for presence of 1PB, differences were observed in relation to Pluset® while Folltropin® showed similar results in all incubation times. Regarding the MII, no difference was observed between the incubation times with FSH Pluset® and Folltropin®. In Experiment III, no difference was observed in the expansion of CCs, presence of 1PB and MII for concentrations evaluated FSH Pluset® and Folltropin®. Therefore, the FSH Pluset® and Folltropin® have the same efficiency in IVM of bovine oocytes. Regarding the incubation time, it is recommended to maintain FSH (Pluset® or Folltropin® throughout the period of IVM, since there was no difference in the results of presence of MII. Furthermore, the concentration of 1.0 ?g/mL of FSH Pluset® and Folltropin® is as effective as 10 ?g/mL and can therefore be used for IVM of oocytes.

Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

Science.gov (United States)

Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

2010-06-01

To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

Science.gov (United States)

Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

2001-12-01

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

Cytotoxicity and mitogenicity assays with real-time and label-free monitoring of human granulosa cells with an impedance-based signal processing technology intergrating micro-electronics and cell biology.

Science.gov (United States)

Oktem, Ozgur; Bildik, Gamze; Senbabaoglu, Filiz; Lack, Nathan A; Akin, Nazli; Yakar, Feridun; Urman, Defne; Guzel, Yilmaz; Balaban, Basak; Iwase, Akira; Urman, Bulent

2016-04-01

A recently developed technology (xCelligence) integrating micro-electronics and cell biology allows real-time, uninterrupted and quantitative analysis of cell proliferation, viability and cytotoxicity by measuring the electrical impedance of the cell population in the wells without using any labeling agent. In this study we investigated if this system is a suitable model to analyze the effects of mitogenic (FSH) and cytotoxic (chemotherapy) agents with different toxicity profiles on human granulosa cells in comparison to conventional methods of assessing cell viability, DNA damage, apoptosis and steroidogenesis. The system generated the real-time growth curves of the cells, and determined their doubling times, mean cell indices and generated dose-response curves after exposure to cytotoxic and mitogenic stimuli. It accurately predicted the gonadotoxicity of the drugs and distinguished less toxic agents (5-FU and paclitaxel) from more toxic ones (cisplatin and cyclophosphamide). This platform can be a useful tool for specific end-point assays in reproductive toxicology. Copyright © 2015 Elsevier Inc. All rights reserved.

New radioimmunoassay for follicle-stimulating hormone in macaques: ovulatory menstrual cycles. [/sup 125/I tracer technique

Energy Technology Data Exchange (ETDEWEB)

Hodgen, G.D.; Wilks, J.W.; Vaitukaitis, J.L.; Chen, H.C.; Papkoff, H.; Ross, G.

1976-07-01

A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75 percent macaque luteinizing hormone (mLH) and 1 percent mFSH, was used to demonstrate the specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone.

Immunological properties of prolactin and studies on a gonadotropin binding inhibitor

International Nuclear Information System (INIS)

Chang, Y.S.

1985-01-01

The physiological role of prolactin in horses has not yet been well defined. With the availability of highly purified ePRL for inducing antibody formation in rabbits and for radiolabeling with Na 125 I, a very sensitive (0.4-0.6 ng/ml) and highly specific homologous RIA for ePRL was developed. A heterologous RIA using 125 I-labeled ovine PRL and anti-ePRL antiserum was also developed and compared to the homologous RIA for ePRL. Of the two systems, it is concluded that this homologous RIA system is more suitable and more reliable for measuring prolactin concentration in horse serum samples. Until now, biochemical information on PRL has not been available for reptilian species. Sea turtle (Chelonia mydas) prolactin was purified from pituitary extracts by selective precipitation, DEAE-cellulose chromatography and gel filtration. Similar to other species of PRL, sea turtle PRL is a 22,000-24,000 daltons protein and contains a high content of glutamic acid, aspartic acid, serine and leucine, the N-terminal amino acid residue. Gonadotropin (FSH) binding inhibitor was partially purified from sheep testes by ammonium sulfate fractionation and ion exchange chromatography. The FSH-BI (molecular weight: 50,000 daltons, estimated by gel filtration) contains a protein moiety necessary for binding inhibitory activity. The inhibition of the binding of 125 I-labeled ovine FSH to its receptor by the FSH-BI is not competitive. Both in vivo and in vitro biological studies of FSH-BI preparations in rats indicated various effects on FSH and LH activities at the gonadal level. These findings suggest a physiological role for FSH-BI in the regulation of reproduction

Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bahnsen, M; Bennett, Patrick

1983-01-01

Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20). No signi......Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20...... affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed...

Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation

Directory of Open Access Journals (Sweden)

Bruno T. Zacharias

2014-12-01

Full Text Available Objective: To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation.Methods: In a prospective study, serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, estradiol (E2 and prolactin (PRL of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD.Results: male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

Studies on binding of radiolabeled thyrotropin to cultured human thyroid cells

International Nuclear Information System (INIS)

Yamamoto, M.; Rapoport, B.

1978-01-01

A line of cultured human thyroid adenoma cells was used in a study designed to compare the stimulatory effect of TSH on cellular cAMP generation with the binding of radiolabeled TSH to the cells. At 37 C, specific binding of [ 125 I]TSH to suspensions of thyroid cells was maximal at 20 min and was reversed by the addition of excess TSH. Unlike the generation of cellular cAMP in response to TSH stimulation, which was maximal at pH 7.5, the binding of [ 125 ]TSH to the cells was maximal at pH 5.5 and progressively declined up to pH 8.5. Increasing NaCl concentrations progressively inhibited cellular binding of TSH; at physiological salt concentrations, almost no TSH binding was detectable. Competitive inhibition studies of [ 125 I]TSH binding to cells revealed a binding site with a dissociation constant of 5.5 x 10 -8 M at pH 7.4. GH, PRL, hCG, FSH, insulin, and glucagon did not compete with [ 125 I)TSH binding. ACTH, however, was a potent inhibitor of [ 125 I]TSH binding. Despite this inhibitory effect on TSH binding, ACTH had little or no effect on cellular cAMP generation. High concentrations of ACTH did not inhibit the biological effect of TSH on cAMP generation. Specific binding of [ 125 I]TSH to empty plastic culture dishes was time dependent, reversible, and displayed a hormonal specificity identical to binding to thyroid cells. The effects of pH and NaCl concentrations on TSH binding to dishes were similarbut not identical to those on cellular binding. This study raises serious questions as to the biological significance of [ 125 I]TSH binding to cultured human thyroid cells

Effects of transferrin on aromatase activity in porcine granulosa cells in vitro.

Directory of Open Access Journals (Sweden)

Małgorzata Duda

2009-01-01

Full Text Available Proliferating cells have an absolute requirement for iron, which is delivered by transferrin with subsequent intracellular transport via the transferrin receptor. Recent studies have reported that transferrin plays a crucial role in the local regulation of ovarian function, apart from its iron-binding characteristic. Therefore, the present study was undertaken to explore the possible role of transferrin in porcine granulosa cells function by examining its influence on aromatase activity, the most important indicator of follicular cell differentiation. In the first series of studies, pig granulosa cells isolated from small, immature follicles were cultured in the presence of transferrin alone (10 microg/ml or 100 microg/ml or with the addition of FSH (100ng/ml. The second series of studies was undertaken to determine transferrin-stimulated granulosa cells ability to aromatize exogenous testosterone (1x10(-7M. One hour after the establishment of cultures an aromatase inhibitor CGS16949A was added to test its influence on estradiol production. After 48 hours, cultures were terminated and cells were processed for immunocytochemical staining of aromatase. Media were frozen for further estradiol level analysis. Positive immunostaining for aromatase was found in all granulosa cell cultures. The intensity of immunostaining was always stronger in cultures supplemented with FSH whereas the addition of transferrin had no effect. Granulosa cells in vitro synthesized the highest amount of estradiol after the addition of FSH and exogenous testosterone as measured radioimmunologically. Concomitant treatment with FSH and transferrin caused an inhibition of FSH-stimulated aromatase activity. The production of estradiol also declined in the presence of FSH, testosterone and transferrin. This study demonstrates that transferrin had a dose-dependent inhibitory effect on FSH-stimulated aromatase activity, which was confirmed by radioimmunoassay. Our results indicate

Gonadotrophins, testosterone and spermatogenesis in neonatally irradiated male rates: evidence for a role of the Sertoli cell in follicle-stimulating hormone feedback

International Nuclear Information System (INIS)

De Jong, F.H.; Sharpe, R.M.

1977-01-01

Peripheral concentrations of FSH in the male rat seem to be regulated in parts by a protein hormone, inhibin, which originates from the testes. In an attempt to ascertain which type of testicular cell secretes inhibin, groups of male rats were irradiated prenatally or on days 4, 6 or 8 of postnatal life, and killed at 21, 51 or 81 days of age together with castrated and intact controls. The concentrations of FSH and LH in the pituitary gland, and FSH, LH and testosterone in the plasma were estimated for each animal, and the numbers of each class of intratubular cell in the testes were calculated. Rats irradiated neonatally had fewer Sertoli cells than controls at all ages studied, while the numbers of Sertoli cells in rats irradiated prenatally were higher than those in controls on day 21. The number of spermatogenic cells was usually decreased in rats irradiated postnatally. In the rats irradiated prenatally normal numbers of spermatogenic cells were found at day 51. Numbers of spermatogenic cells were significantly correlated with the number of Sertoli cells at the ages of 51 and 81 days. The concentration of FSH in the plasma usually increased in the postnatally irradiated animals on days 21 and 51, but not on day 81; prenatal irradiation did not result in altered levels of FSH at any age. Peripheral levels of LH and testosterone were not affected by irradiation. The concentration of FSH in the plasma was negatively correlated with the number of Sertoli cells in all age groups, whereas significant correlations between the levels of FSH and the number of spermatogenic cells were only found at days 51 and 81. It is concluded from these data that the Sertoli cell is the most likely source of inhibin. (author)

Diurnal rhythms in gonadotropins and progesterone in lactating and photoperiod induced acyclic hamsters

International Nuclear Information System (INIS)

Bridges, R.S.; Goldman, B.D.

1975-01-01

Levels of LH, FSH, and progesterone in serum were measured in lactating hamsters and in hamsters in which acyclicity was induced with altered photoperiod. Lactating hamsters were found to have low titers of LH, FSH, and progesterone in serum at 0900 (lights on 0500--1900) on Days 4, 9, 14, and 19 of lactation and increased levels of these hormones at 1600. Levels of LH and FSH in serum at both 0900 and 1600 remained relatively constant throughout lactation. In contrast, levels of progesterone in serum obtained at both 0900 and 1600 sampling times increased as lactation progressed. Ovariectomy on Day 9 of lactation reduced serum levels of progesterone at both 0900 and 1600 and eliminated the afternoon surge in progesterone in animals bled 5 days after surgery. The levels and pattern of LH in serum remained unchanged after ovariectomy in lactating hamsters. However, serum FSH levels in the ovariectomized, lactating animals were elevated at both 0900 and 1600 when compared to levels present in intact, lactating hamsters bled at the same times. Females which were acyclic due to altered photoperiod displayed similar patterns of LH, FSH, and progesterone in serum. Levels of LH, FSH, and progesterone in serum were low at 1000 (lights on 0500--1500) and were increased 2 to 10 fold at 1500. Ovariectomy was followed by lower progesterone levels in serum at 1000 and 1500 and eliminated the afternoon rise of this hormone. Serum levels of LH were unaffected by ovariectomy. As in lactating hamsters, levels of FSH in serum were elevated 3--4 days following ovariectomy at both bleeding times, but the levels were higher at 1500. These results indicate that acyclicity induced by lactation or exposure to a short photoperiod is characterized by similar diurnal patterns of circulating hormones in the hamster

[Health economic consequences of the choice of follicle stimulating hormone alternatives in IVF treatment].

Science.gov (United States)

Poulsen, Peter Bo; Højgaard, Astrid; Quartarolo, Jens Piero

2007-04-02

There is a choice between two types of hormones for stimulation of the follicles in IVF treatment - recombinant FSH and the urine-derived menotrophin. A literature review by NICE (2004) in the United Kingdom documented that the two types of hormones were equally effective and safe, which is why it was recommended to use the cheaper urine-derived hormone. Based on the EISG study (European and Israeli Study Group), the aim was to analyse the health economic consequences of the choice between the two types of hormone in IVF treatment in Denmark. In a prospective cost-effectiveness analysis (health care sector perspective), menotrophin and recombinant FSH (Gonal-F) were compared. Differences in costs were compared with differences in effects of the two alternatives. The total costs for the average patient are lower when using menotrophin compared with recombinant FSH. Furthermore, the cost per clinical pregnancy was lower with menotrophin compared with recombinant FSH hormone. Menotrophin is therefore less expensive both for the patient as well as for the health care sector. The use of menotrophin instead of recombinant FSH can result in savings of up to DKK 16 million on the drug budget--savings that could finance 1,400 additional IVF cycles. The analysis shows that urine-derived menotrophin is a cost-effective alternative to recombinant FSH with a potential for considerable savings for patients as well as the public drug budget.

Endocrine basis of prolificacy in the Booroola Merino

International Nuclear Information System (INIS)

Bindon, B.M.; Piper, L.R.; Hillard, M.A.; O'Shea, T.; Findlay, J.K.

1991-01-01

Recent research confirms that the ovulation rate of the sheep can be increased by short term elevation of plasma follicle stimulating hormone (FSH) concentrations during the early follicular phase. Studies of the Booroola Merino suggest that the F gene probably acts through this pathway. That is, there are gene specific differences in plasma FSH early in the follicular phase. There is no evidence that the ovary of the Booroola is especially sensitive to exogenous FSH. In contrast, increased ovulation rate in response to selection within the Finn breed (in Ireland) cannot be attributed to any changes in plasma FSH concentrations. The elevated plasma FSH in the Booroola female may result from a deficiency of ovarian inhibin, the major feedback regulator of FSH. This has been demonstrated by both bioassay of inhibin in ovarian cytosol and radioimmunoassay of inhibin in peripheral plasma. It is not yet known if this low inhibin is attributable to a derangement of the inhibin genes in the Booroola or to the fact that their follicles are smaller and produce less follicular fluid than those of other sheep. The increased ovulation rate of Merinos following immunization against inhibin confirms the importance of this hormone as a key regulator of ovarian function. At present there are no known effects of the Booroola gene on the gonad of the male or on the hormones that regulate testis function. (author). 14 refs, 4 figs, 6 tabs

Action-Dependent Photobiomodulation on Health, Suboptimal Health, and Disease

Directory of Open Access Journals (Sweden)

Timon Cheng-Yi Liu

2014-01-01

Full Text Available The global photobiomodulation (PBM on an organism was studied in terms of function-specific homeostasis (FSH and scale-free functional network in this paper. A function can be classified into a normal function in its FSH and a dysfunctional function far from its FSH. An FSH-specific stress (FSS disrupting an FSH can also be classified into a successful stress in its FSS-specific homeostasis (FSSH and a chronic stress far from its FSSH. The internal functions of an organism can be divided into essential, special nonessential, and general nonessential functions. Health may be defined as a state of an organism in which all the essential and special nonessential functions are normal or their stresses are successful. Suboptimal health may be defined as a state of a disease-free organism in which only some special nonessential functions are dysfunctional in comparison with its healthy state. Disease may be defined as a state of an organism which is not in both health and suboptimal health. The global PBM of health, suboptimal health, or disease suggested that the PBM may depend on the organism action.

Assessment of ovarian reserve in euthyroid adolescents with Hashimoto thyroiditis.

Science.gov (United States)

Pirgon, Ozgur; Sivrice, Cigdem; Demirtas, Hakan; Dundar, Bumin

2016-01-01

We aimed to investigate the ovarian function and reserve in euthyroid adolescents (TSH Hashimoto thyroiditis (HT). This case-control study included 30 adolescent girls (mean age 15.1 ± 1.4 years) newly diagnosed as HT with presence of high thyroid antibodies with gland heterogeneity in ultrasound and age-matched 30 healthy female subjects. Anti-ovarian antibody (AOAb), LH/FSH ratio, estradiol, anti-mullerian hormone (AMH), inhibin-B, total testosterone, antral follicle count, ovarian volumes and uterine length were measured. The clinical, laboratory, and ultrasound data of the HT and control groups were compared. There were no significant differences between the girls with HT and healthy controls in relation to LH/FSH ratio, estradiol and inhibin-B levels. AOAb (p = 0.02), AMH (p = 0.007) and total testosterone levels were higher in HT group than the control group (p = 0.03). AOAb level was found to be positively correlated with LH/FSH ratio (p = 0.03), AMH (p = 0.01) and inhibin-B (p thyroiditis had normal ovarian reserve based on measurements of AMH, inhibin B, FSH, LH/FSH ratio, estradiol and antral follicle counts.

Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

KAUST Repository

Zhang, Xiaomei

2010-03-04

We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

Risk charts to identify low and excessive responders among first-cycle IVF/ICSI standard patients

DEFF Research Database (Denmark)

la Cour Freiesleben, N; Gerds, Thomas Alexander; Forman, Julie Lyng

2011-01-01

Ovarian stimulation carries a risk of either low or excessive ovarian response. The aim was to develop prognostic models for identification of standard (ovulatory and normal basal FSH) patients’ risks of low and excessive response to conventional stimulation for IVF/intracytoplasmic sperm injection....... Prospectively collected data on 276 first-cycle patients treated with 150 IU recombinant FSH (rFSH)/day in a long agonist protocol were analysed. Logistic regression analysis was applied to the outcome variables:low (seven or less follicles) and excessive (20 or more follicles) response. Variables were woman......’s age, menstrual cycle length, weight or body mass index, ovarian volume, antral follicle count (AFC) and basal FSH. The predictive performance of the models was evaluated from the prediction error (Brier score, %) where zero corresponds to a perfect prediction. Model stability was assessed using 1000...

Is the FSHR 2039A>G variant associated with susceptibility to testicular germ cell cancer?

DEFF Research Database (Denmark)

Bang, A K; Busch, A S; Almstrup, K

2018-01-01

Testicular germ cell cancer (TGCC) is derived from germ cell neoplasia in situ (GCNIS), which arises due to niche disturbances affecting the Sertoli cells. It is believed that exogenous endocrine factors have a crucial role in governing neoplastic transformation but on a strong hereditary...... background. Follicle-stimulating hormone (FSH) is the major regulatory hormone of the Sertoli cells. FSH signalling-related single-nucleotide polymorphisms (SNPs) have previously been shown to affect FSH action in men at different levels. We aimed to investigate whether three FSH-related SNPs (FSHR 2039A......>G, FSHR -29G>A and FSHB -211G>T) are associated with development of TGCC. A total of 752 Danish and German patients with TGCC from two tertiary andrological referral centres were included. Three control groups comprising 2020 men from the general population, 679 fertile men and 417 infertile men, were...

Clinical significance of determination serum sex hormones levels in patients with secondary amenorrhea

International Nuclear Information System (INIS)

Jiang Hua

2007-01-01

Objective: To explore the clinical significance of changes of serum sex hormones levels in patients with secondary amenorrhea. Methods: Serum levels of E 2 , FSH, LH, PRL and P were detected with RIA in 33 patients with secondary amenorrhea and 30 controls. Results: In the patients, the serum E 2 levels were significantly lower and FSH, LH, PRL and P levels were significantly higher than those in controls (P 2 , FSH, LH, PRL and P levels is of help for assessment of severity of secondary amenorrhea as well as outcome prediction. (authors)

Effect of pituitary gonadotrophins on tritiated thymidine uptake by rat ovary

International Nuclear Information System (INIS)

Nakano, Ryosuke; Mizuno, Tadayoshi; Katayama, Kazuaki; Hayashi, Kaname; Tojo, Shimpei

1975-01-01

The effect of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on the follicular growth in the ovary of the hypophysectomized rat was investigated using autoradiography. The numbers of DNA-synthesizing nuclei in the granulosa cell were measured by autoradiography after flashlabelling with tritiated ( 3 H) thymidine. The frequency of 3 H-thymidine labelled nuclei in the granulosa cell enhanced in the presence of FSH. In contrast, LH had no significant effect on thymidine uptake. The result suggests that FSH stimulates follicle cell division, whereas LH does not. (orig.) [de

Gonadotropins, their receptors, and the regulation of testicular functions in fish

NARCIS (Netherlands)

Schulz, Rüdiger W; Vischer, H F; Cavaco, J E; Dos Santos Rocha, M.E.; Tyler, R.C.; Goos, H.J.; Bogerd, J.

The pituitary gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate steroidogenesis and spermatogenesis by activating receptors expressed by Leydig cells (LH receptor) and Sertoli cells (FSH receptor), respectively. This concept is also valid in fish, although the

Treatment preferences and trade-offs for ovulation induction in clomiphene citrate-resistant patients with polycystic ovary syndrome

NARCIS (Netherlands)

Bayram, Neriman; van Wely, Madelon; van der Veen, Fulco; Bossuyt, Patrick M. M.; Nieuwkerk, Pythia

2005-01-01

Objective: To investigate patient preferences and trade-offs for laparoscopic electrocautery of the ovaries relative to ovulation induction with recombinant FSH (rFSH) in patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Design: Assessment of preferences and

Intravenous iron replacement therapy in eugonadal males with iron-deficiency anemia: Effects on pituitary gonadal axis and sperm parameters; A pilot study

Directory of Open Access Journals (Sweden)

Ashraf Soliman

2014-01-01

Full Text Available Aim of the study: To evaluate semen parameters and to assess serum FSH, LH, Testosterone (T concentrations before and 12 weeks after intravenous iron therapy (800-1200 mg elemental iron therapy - IVI in adults with iron-deficiency anemia (IDA. Materials and Methods: We studied 11 eugonadal adults with IDA, aged 40 ± 5 years, due to defective intake of iron. Anemia was diagnosed when hemoglobin (Hb was equal or below 10 g/dl. Serum iron, total iron-binding capacity (TIBC and ferritin concentrations confirmed the diagnosis of IDA. Basal serum concentrations of FSH, LH, and T were measured. Semen parameters were evaluated before and 6-7 weeks after IVI therapy. Results: After IVI therapy and correction of anemia, a significant increase of Hb from 8.1 ± 1.17 g/dL to 13.1 ± 0.7 g/dL was observed and was associated with an increase of T (from 12.22 ± 1.4 nmol/L to 15.9 ± 0.96 nmol/L; P < 0.001, FSH (from 2.82 ± 0.87 to 3.82 ± 1.08 IU/L; P = 0.007, and LH (from 2.27 ± 0.9 to 3.82 ± 1.5 IU/L; P = 0.0002. Total sperm count (TSC increased significantly from 72 ± 17.5 million/ml to 158 ± 49 million/mL (P < 0.001, rapid progressive sperm motility (RPM increased from 22 ± 9.4 to 69 ± 30 million/ml (P < 0.001, and sperms with normal morphology (NM increased from 33 ± 5 to 56 ± 7 million/ml (P < 0.001. Increment in Hb concentration was correlated significantly with LH, FSH, and T concentrations after IVI (r = 0.69 and r = 0.44, r = 0.75, respectively; P < 0.01. The increment in serum T was correlated significantly with increments in the TSC and total sperm motility and RPM (r = 0.66, 0.43, and 0.55, respectively; P < 0.001 but not with gonadotrophin levels. Conclusion: Our study proved for the first time, to our knowledge, that correction of IDA with IVI is associated with significant enhancement of sperm parameters and increased concentrations of serum LH, FSH, and T. These effects on spermatogenesis are reached by an unknown mechanism and

DESENVOLVIMENTO DE FOLÍCULOS PRÉ-ANTRAIS BOVINOS IN VITRO EM MONOCAMADA DE CÉLULAS OVARIANAS IN VITRO DEVELOPMENT OF BOVINE PREANTRAL FOLLICLES IN MONOLAYER OF OVARIAN CELLS

Directory of Open Access Journals (Sweden)

Luís Fabiano Santos da Costa

2001-04-01

Full Text Available O presente trabalho teve como objetivos determinar a influência de células ovarianas no desenvolvimento in vitro de folículos pré-antrais, avaliar a viabilidade das células ovarianas em monocamada e a influência do soro na manutenção de folículos pré-antrais in vitro. Folículos pré-antrais (FPs e células ovarianas foram isolados de ovários de fetos bovinos, com idade entre 6 e 8 meses de gestação, oriundos de matadouro. Células ovarianas em monocamada foram cultivadas em meio TCM-199, e a viabilidade celular, após o cultivo na presença ou ausência de FSH, foi determinada com o corante vital azul de tripan. FPs foram distribuidos em quatro tratamentos e cultivados em TCM-199 modificado, contendo soro de novilho castrado (SNC, SNC em monocamada de células ovarianas (MCO, MCO com FSH ou meio definido com álcool polivinílico (PVA como macromolécula. A viabilidade celular não foi afetada em conseqüência da presença ou ausência de FSH. No entanto, houve um incremento significativo no tamanho dos FPs cultivados na presença de SNC, MCO e FSH (PThe aim of the present work was to determine the influence of ovarian cells in the in vitro development of preantral follicles (PF. The viability of monolayer ovarian cells and the effect of the serum in the survive of in vitro PF was also investigated. Ovarian cells and PF were isolated from ovaries of bovine fetus between 6 and 8 months of pregnancy, obtained in a slaughterhouse. Monolayer of ovarian cells were cultured in a modified TCM-199 in the presence and absence of FSH and its viability after incubation was determined with Trypan Blue. PFs were divided in four different treatments, cultured in modified TCM-199, containing serum of castrated steer (SCS, SCS in monolayer of ovarian cells (MOC, MOC with FSH or a defined medium with polyvinyl alcohol (PVA as macromolecule. The cellular viability was not affected by the presence or absence of FSH. However, PFs had a significant

Apparent primary follicle-stimulating hormone deficiency is a rare cause of treatable male infertility

NARCIS (Netherlands)

Giltay, JC; Deege, M; Blankenstein, RA; Kastrop, PMM; Wijmenga, C; Lock, TTWT

Objective: To find the underlying defect in a case of primary FSH deficiency and to estimate the beneficial effect of FSH treatment. Design: Case report. Setting: University hospital fertility clinic. Patient(s): Normal, healthy, 37-year-old male patient with severe oligoteratozoospermia.

Hormonal control of spermatogenesis: expression of FSJH receptor and androgen receptor genes

NARCIS (Netherlands)

L.J. Blok (Leen)

1992-01-01

textabstractFSH and testosterone are the main hormonal regulators of spermatogenesis. The actions of androgens and FSH are mediated by their respective receptors. Receptor gene expression (mRNA and protein). is an important determinant of hormone action. Biochemical aspects of the regulation of

FSH (Follicle-Stimulating Hormone) Test

Science.gov (United States)

... for Teens (Ages 13-18) Screening Tests for Young Adults (Ages 19-29) Screening Tests for Adults (Ages 30- ... what is expected for a youth within this age range. Some of the causes for delayed puberty can ...

Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

Science.gov (United States)

Fouda, Usama M; Sayed, Ahmed M

2011-12-01

To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males.

Science.gov (United States)

Zhang, Zhiwei; Lau, Shuk-Wa; Zhang, Lingling; Ge, Wei

2015-10-01

Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.

Serum gonadotropins levels in childhood

International Nuclear Information System (INIS)

Hertogh, R. De; Vankrieken, L.; Wolter, R.; Vliet, G. Van

1989-01-01

The complex changes in serum LH and FSH levels from infancy to adulthood are diversely evaluated by radioimmunoassays or bioassays. The relative lack of sensitivity and specificity of radioimmunoassay, using polyclonal antibodies, could possibly be overcome by new immunoradiometric assays, using specific antibodies to LH and FSH. Significant differences were indeed observed between radioimmunoassays and immunoradiometric assays. During the prepubertal period, LH levels, measured by the immunoradiometric assays, were below the sensitivity of the method in the majority of the samples. LH levels were, however, well detectable when measured with radioimmunoassay, showing the heterogeneity of circulating LH structures. At the onset of puberty, LH levels increased at least 3 to 4 times in both sexes, when measured with immunoradiometric assays, whereas their increase was only 20 to 60% with the radioimmunoassays. FSH levels remained well detectable in the prepubertal period whether measured by immunoradiometric or radioimmunoassays. At pubertal onset, FSH increase in both sexes was more important in the immunoradiometric assays. The results obtained with immunoradiometric assays give a better insight into the quantitative and qualitative function of the gonadotropes during childhood. The almost complete absence of LH during the prepubertal period and the steep increase at the onset of puberty better reflects the reported data obtained with bioassays. The persistance of significant levels of FSH in the prepubertal ages, and the lesser increase at the onset of puberty, when compared with LH, illustrates that the individual regulation of LH and FSH secretion vary over time and is influenced by developmental factors. (author)

Serum gonadotropins levels in childhood. Critical comparison between immunoradiometric assays and radioimmunoassays

Energy Technology Data Exchange (ETDEWEB)

Hertogh, R. De; Vankrieken, L. (Physiology of Human Reproduction Research Unit, University of Louvain, School of Medicine, Brussels (Belgium)); Wolter, R.; Vliet, G. Van (Hopital Universitaire des Enfants, Reine Fabiola, Free University of Brussels (Belgium))

1989-01-01

The complex changes in serum LH and FSH levels from infancy to adulthood are diversely evaluated by radioimmunoassays or bioassays. The relative lack of sensitivity and specificity of radioimmunoassay, using polyclonal antibodies, could possibly be overcome by new immunoradiometric assays, using specific antibodies to LH and FSH. Significant differences were indeed observed between radioimmunoassays and immunoradiometric assays. During the prepubertal period, LH levels, measured by the immunoradiometric assays, were below the sensitivity of the method in the majority of the samples. LH levels were, however, well detectable when measured with radioimmunoassay, showing the heterogeneity of circulating LH structures. At the onset of puberty, LH levels increased at least 3 to 4 times in both sexes, when measured with immunoradiometric assays, whereas their increase was only 20 to 60% with the radioimmunoassays. FSH levels remained well detectable in the prepubertal period whether measured by immunoradiometric or radioimmunoassays. At pubertal onset, FSH increase in both sexes was more important in the immunoradiometric assays. The results obtained with immunoradiometric assays give a better insight into the quantitative and qualitative function of the gonadotropes during childhood. The almost complete absence of LH during the prepubertal period and the steep increase at the onset of puberty better reflects the reported data obtained with bioassays. The persistance of significant levels of FSH in the prepubertal ages, and the lesser increase at the onset of puberty, when compared with LH, illustrates that the individual regulation of LH and FSH secretion vary over time and is influenced by developmental factors. (author).

Influence of Anthropometric Measurements on Abnormal Gonadotropin Secretion in Women with Polycystic Ovary Syndrome

International Nuclear Information System (INIS)

Haider, S.; Mannan, N.; Qureshi, M. A.; Khan, A.

2014-01-01

Objective: To evaluate the influence of anthropometric measurements on abnormal gonadotropin secretion in patients with polycystic ovary syndrome (PCOS). Study Design: Cross-sectional study. Place and Duration of Study: The Institute of Basic Medical Sciences (IBMS), DUHS in collaboration with Gynae/infertility clinics of the Civil Hospital and Lady Dufferin Hospital, Karachi, from October 2010 to February 2011. Methodology: One hundred and sixty three oligomenorrhic PCOS women of reproductive age (18 - 40 years) fulfilling the revised Rotterdam 2003 criteria were studied. The data recorded on a prescribed proforma included current age, age at menarche, menstrual irregularities, presence of hirsuitism, acne, infertility, familial nature, blood pressure, BMI and waisthip ratio. Blood samples for gonadotropin assay were taken randomly on day 6th to 30th of menstrual cycle, in a gel tube. Hormonal assay was performed using chemiluminescent immunoassay. Kruskul Wallis test was used to assess the influence of BMI levels on LH:FSH values. Results: The mean weight was 66.14 +- 11.02 kg and mean BMI was 27.03 +- 4.42 kg/m2. There was no significant difference in mean LH/FSH ratio (p=.575) among BMI groups. However, there was a positive correlation between BMI and LH:FSH ratio (p=0.04, r=0.155). Conclusion: There was high frequency of obesity (69%) in women with PCOS. Although no significant difference was found between mean LH:FSH ratio among different BMI groups levels but significant correlation between BMI levels and LH: FSH suggested that there was positive relation between BMI and LH: FSH. (author)

[The lh-rh-test in men with fertility disorders (author's transl)].

Science.gov (United States)

Krause, W; Höbel, W

1976-11-01

89 mal patients with fertility disorders underwent a test with 50 mug synthetic LH-RH. The basal levels of FSH and LH are elevated in patients with azoospermia, with testicular atrophy, varicocele and Klinefelters syndrome. They increase with age. After stimulation with LH-RH the highest relative peaks (maximal value divided by control value) of LH are seen younger patients, in those with varicocele, and oligozoospermia. The FSH-values do not differ significantly between these groups. Low relative peaks of LH are seen in older patients. In Klinefelter's syndrome the relative peaks of FSH and LH are significantly lowered.

Changes in serum sexual hormone levels in women with infertility

International Nuclear Information System (INIS)

Hu Mingjiang; Zhu Benxing; Xu Yujie

2001-01-01

In order to understand the clinical effects of serum sexual hormone level changes on infertility, 84 women with infertility were divided into four groups. With the use of RIA, levels of FSH, LH, PRL, E 2 , t and P in serum of 84 women with infertility were measured in their follicular phase. It was showed that the serum levels of FSH, LH, PRL, E 2 , T and P in four infertility groups were all higher than the given normal standards respectively. Except E 2 (P 2 and P coincided with the percentages of the patients with the higher ratio of FSH to LH

Patients with 47, XXX karyotype who experienced premature ovarian failure (POF): two case reports.

Science.gov (United States)

Sugawara, Nobuo; Maeda, Machiko; Manome, Tomomi; Nagai, Rie; Araki, Yasuhisa

2013-10-01

Pubertal onset and sexual development are usually normal in 47, XXX individuals; however, we report two cases of premature ovarian failure (POF) in infertile women with trisomy X. Chromosome analysis was conducted with G-banding and fluorescence in situ hybridization using X- and Y-bearing probe. Hormonal administration was primarily Kaufmann's treatment or long-term estradiol treatment, followed by withdrawal bleeding from estrogen and progesterone. Two patients with trisomy X, aged 31 (patient 1) and 27 years (patient 2), were diagnosed with POF due to hypergonadotropic hypogonadism. Their ovaries were small. Patient 1 had a FSH level of 44.6 mIU/ml and patient 2 had a FSH level of 74.6 mIU/ml. In patient 1, with Kaufmann's treatment, the FSH decreased to 13.5 mIU/ml; however, follicle growth did not occur following HMG stimulation. In patient 2, FSH did not decrease despite Kaufmann's treatment; therefore, she was given a GnRH agonist and her FSH level decreased to 7.1 mIU/ml. However, her ovaries never responded to HMG stimulation. We report on two patients with a 47, XXX karyotype who became infertile due to POF. We recommend that when a patient is diagnosed with trisomy X, the possibility of POF must be strongly considered.

Laser homeostatics on delayed onset muscle soreness

Energy Technology Data Exchange (ETDEWEB)

Liu, T C Y; Fu, D R; Liu, X G; Tian, Z X, E-mail: liutcy@scnu.edu.cn [Lab Laser Sports Medicine, South China Normal University, University Town, Guangzhou, GD 510006 (China)

2011-01-01

Delayed onset muscle soreness (DOMS) and its photobiomodulation were reviewed from the viewpoint of function-specific homeostasis (FSH) in this paper. FSH is a negative-feedback response of a biosystem to maintain the function-specific fluctuations inside the biosystem so that the function is perfectly performed. A stressor may destroy a FSH. A stress is a response of a biosystem to a stressor and may also be in stress-specific homeostasis (StSH). A low level light (LLL) is so defined that it has no effects on a function in its FSH or a stress in its StSH, but it modulate a function far from its FSH or a stress far from its StSH. For DOMS recovery, protein metabolism in the Z-line streaming muscular cell is the essential process, but the inflammation, pain and soreness are non-essential processes. For many DOMS phenomena, protein metabolism in the Z-line streaming muscular cell is in protein metabolism-specific homeostasis (PmSH) so that there are no effects of LLL although the inflammation can be inhibited and the pain can be relieved. An athlete or animal in the dysfunctional conditions such as blood flow restriction and exercise exhaustion is far from PmSH and the protein metabolism can be improved with LLL.

A comparison between r-LH and urinary supplements containing LH activity in patients undergoing the microdose GnRH agonist flare protocol for in-vitro fertilization: a pilot study.

Science.gov (United States)

Shavit, Tal; Agdi, Mohammed; Son, Weon Y; Hasson, Josseph; Dahan, Michael H

2016-08-01

The aim of this study was to compare pregnancy rates and stimulation parameters in patients with diminished ovarian reserve, who were treated with recombinant human luteinizing hormone (r-LH) or menopausal gonadotropins (hMG), as part of a microdose flare protocol. A retrospective cohort study was performed. Comparisons between the group that was stimulated with r-LH plus follicle stimulating hormone (FSH) to those treated with hMG and FSH, were performed. Measurements included: medication doses, number of oocyte collected, number of embryos obtained, pregnancy and clinical pregnancy rates. Patients in the r-LH group (N.=40) had significant higher clinical pregnancy rates (33% vs. 14%; P=0.04) and used lower dose of LH (1938 IU vs. 2807 IU; P=0.02) compared to patients that were stimulated with hMG (N.=39). r-LH may offer advantages for the treatment of diminished ovarian reserve when performing a microdose flare protocol when compared to hMG. Both larger and prospective studies should be carried out to confirm these findings.

Fluoride-induced disruption of reproductive hormones in men

International Nuclear Information System (INIS)

Ortiz-Perez, Deogracias; Rodriguez-Martinez, Manuel; Martinez, Flavio; Borja-Aburto, V.H.; Castelo, Julio; Grimaldo, J.I.; Cruz, Esperanza de la; Carrizales, Leticia; Diaz-Barriga, Fernando

2003-01-01

Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group--HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs

Expression of antiapoptosis gene survivin in luteinized ovarian granulosa cells of women undergoing IVF or ICSI and embryo transfer: clinical correlations

Directory of Open Access Journals (Sweden)

Varras Michail

2012-09-01

Full Text Available Abstract Background The purpose of the study was to determine the incidence of survivin gene expression in human granulosa cells during ovarian stimulation in Greek women with normal FSH levels, undergoing IVF or ICSI and to discover any correlation between levels of gene expression and clinical parameters, efficacy of ovulation or outcomes of assisted reproduction. Methods Twenty nine women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded and the granulosa cells were analyzed for each patient separately using quantitative reverse transcription polymerase chain reaction analysis for survivin gene expression with internal standard the ABL gene. Results The ABL and survivin mRNA were detected in granulosa cells in 93.1%. The expression levels of survivin were significantly lower in normal women (male infertility factor compared to women with tubal infertility factor (p = 0.007. There was no additional statistically significant correlation between levels of survivin expression and estradiol levels or dosage of FSH for ovulation induction or number of dominant follicles aspirated or number of retrieved oocytes or embryo grade or clinical pregnancy rates respectively. Conclusions High levels of survivin mRNA expression in luteinized granulosa cells in cases with tubal infertility seem to protect ovaries from follicular apoptosis. A subpopulation of patients with low levels of survivin mRNA in granulosa cells might benefit with ICSI treatment to bypass possible natural barriers of sperm-oocyte interactions.

Gonadotropins studies in female egyptian subjects under different physiological conditions

International Nuclear Information System (INIS)

El-Nabarawy, F.S.; Megahed, Y.M.; Ibrahim, M.

2002-01-01

This study is concerned with the role of the hypothalamic hypophyseal regulatory hormonal mechanisms in the control of gonadal secretions in a selected normal egyptian female subjects with varying ages under different physiological conditions. The study allowed precise definition of the modulator influence of a number of key factors triggering appropriate alteration in circulating serum levels of FSH and LH determined by IRMA technique in pre-pubertal female children (9-11), post-pubertal adolescents females (13-16). Adult married females (27-33) and post-menopausal (58-63). The levels of FSH and LH were increased markedly with age but children less than 11 years old had only nocturnal increase in levels of FSH (p.O.I) and LH(P< 0.001). post-pubertal aged girls had significant nocturnal elevation only of LH levels (P< 0.001), adult married females did not exhibit significant difference in gonadotropin concentrations. whereas significant elevation in FSH and LH levels (P<0.001) in post-menopausal females were observed

Different serotonin receptor types participate in 5-hydroxytryptophan-induced gonadotropins and prolactin release in the female infantile rat.

Science.gov (United States)

Lacau-Mengido, I M; Libertun, C; Becú-Villalobos, D

1996-05-01

Serotonin (5-HT) receptors can be classified into at least three, possibly up to seven, classes of receptors. They comprise the 5-HT1, 5-HT2, and 5-HT3 classes, the "uncloned' 5-HT4 receptor and the recombinant receptors 5-ht5, 5-ht6 and 5-ht7. We investigated the role of different serotonin receptor types in a neuroendocrine response to the activation of the serotonergic system. Female immature rats were chosen as an experimental model as it has been shown that during the 3rd week of life, and not at later developmental stages, 5-hydroxytryptophan (5-HTP, a serotonin precursor) induces gonadotropin release in females and not in males. Besides, at this age, serotonin releases prolactin in both sexes. 5-HTP (50 mg/kg) released prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as expected. Ketanserin (5-HT2A antagonist) and methysergide (5-HT2C antagonist) blocked 5-HTP-induced prolactin release, but did not block the LH or FSH responses. Ondansetron (5-HT3 receptor antagonist) did not modify prolactin response to 5-HTP, whereas it blocked 5-HTP-induced LH and FSH release. Propranolol (5-HT1 and beta-adrenergic antagonist) blocked prolactin, LH and FSH release induced by 5-HTP. The 5-HT2C agonist 1-(3-chlorophenyl)piperazine dihydrochloride released prolactin, without modifying LH or FSH release. Methyl-quipazine and phenylbiguanide (5-HT3 agonists) increased both LH and FSH levels, without altering prolactin secretion. The present experiments indicate that serotonin acting at the 5-HT3 receptor mediates LH and FSH release in infantile female rats, whereas 5-HT2C or 2A receptor types participate in the release of prolactin at this age. 5-HT1 receptor type may be involved in the release of the three hormones, though a beta-adrenergic component of the response cannot be discarded.

Genetic and clinical predictors of ovarian response in assisted reproductive technology

Science.gov (United States)

Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

2017-08-01

Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression

International Nuclear Information System (INIS)

Myllymaeki, S.A.; Karjalainen, M.; Haavisto, T.E.; Toppari, J.; Paranko, J.

2005-01-01

Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening

Anti-Müllerian hormone, follicle stimulating hormone, antral follicle count, and risk of menopause within 5 years.

Science.gov (United States)

Kim, Catherine; Slaughter, James C; Wang, Erica T; Appiah, Duke; Schreiner, Pamela; Leader, Benjamin; Calderon-Margalit, Ronit; Sternfeld, Barbara; Siscovick, David; Wellons, Melissa

2017-08-01

To evaluate the ability of concentration of anti-Müllerian hormone (AMH), antral follicle count (AFC), and concentration of follicle stimulating hormone (FSH) to predict the onset of menopause. The Coronary Artery Risk Development in Young Adults Study (CARDIA) Women's Study was an ancillary study to CARDIA, a population-based study of adults aged 18-30 years followed for 3 decades. For this report, participants were women (n=426) who had attended the CARDIA year 15-16 (2000-2001) examination, had at least one ovary, were not pregnant, and underwent serum AMH and FSH measurement and transvaginal ultrasonography in 2002-2003. The probability of menopause in 5 years based upon AMH, FSH, and AFC. The mean age of the women at the time of AMH, FSH, and AFC assessment was 43 years. The cumulative incidence of menopause at 25 years (or follow-up) was 27% (n=426), and the incidence within 5 years was 13% (n=55). Among women aged 45-49 years, undetectable AMH concentrations were associated with a greater than 60% probability of menopause within 5 years, whereas approximately 1/3 of women with no or just one antral follicle experienced menopause within 5 years. Both low and high concentrations of FSH were associated with greater odds of menopause than intermediate concentrations. Models with multiple markers did not improve the prediction of menopause over that afforded by models with single markers. The ability to predict onset of menopause was improved with any of the three menopausal markers in addition to age. AMH concentrations were more closely associated with menopause than AFC or FSH. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea.

Science.gov (United States)

Berardelli, Rita; Gianotti, Laura; Karamouzis, Ioannis; Picu, Andreea; Giordano, Roberta; D'Angelo, Valentina; Zinnà, Domenico; Lanfranco, Fabio; Ghigo, Ezio; Arvat, Emanuela

2011-10-01

Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility. We studied the effects of a GnRHa, cetrorelix (CTX 3.0 mg), in six women with HA (age 30.7 ± 3.2 years; BMI 21.5 ± 1.7 kg/m(2)) and six control subjects (CS, 28.2 ± 0.6 years; 22.6 ± 0.9 kg/m(2)) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4 h (08.00-12.00 am) before, +24 h and +96 h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72 h after CTX. CS: CTX reduced (p < 0.05) LH, FSH, and oestradiol (nadir at +12 h, +24 h, and +24 h); LH rebounded at +96 h, FSH and oestradiol recovered at +48 h and +72 h. The 4-h evaluation showed LH and FSH reduction (p < 0.05) at +24 h, with LH rebound at +96 h. HA: CTX reduced (p < 0.05) LH, FSH, and oestradiol, (nadir at +24 h, +48 h, and +48 h, recovery at +48 h, +72 h, and +96 h). The 4-h evaluation showed gonadotropin reduction (p < 0.05) 24 h after CTX, without any rebound effect. One single CTX dose still modulates gonadotropin secretion in HA. Its 'paradoxical' stimulatory effect on gonadotropins needs to be verified after prolonged administration.

Study of hormonal status of surgical patients with endometrial carcinoma

International Nuclear Information System (INIS)

Musina, R.Kh.; Kiseleva, N.S.; Modnikov, O.P.

1987-01-01

A radioimmunoassay was conducted in the pituitary-ovary and pituitary-adrenals systems in 37 cases of endometrial carcinoma treatment and 1, 3, 5 and 14 days after extirpation of the uterus and appendages. The levels of follicle - stimulating (FSH) and luteinizing (LH) hormones of the pituitary, prolactin, ACTH, estradiol, progesterone, testosterone, cortisol and aldosterone were studied. Such disturbances as decreased production of FSH, LH, progesterone and testosterone were observed before operation. Surgery was followed by a considerable rise in prolactin production and basal levels of FSH and LH, a decrease in estradiol, progesterone and testosterone concentrations and was accompanied by a sizeable release of cortisol and aldosterone

Effects of X-irradiation on gonadotropin secretion in rat anterior pituitary cells

International Nuclear Information System (INIS)

Li Xinmin; Liu Shuzheng

1988-01-01

The dispersed rat anterior pituitary cells cultured in 3 days was exposed to single doses of X-irradiation in the range of 0.5-8.0 Gy. LH and FSH contents in both the supernatant and the cells were measured. The LH secretion was significantly increased at the doses greater than 0.5 Gy and FSH secretion was also significantly enhanced at the dose of 4.0 Gy. The cellular contents of both LH and FSH remained near the control levels. It is concluded that gonadotropin secretion can be stimulated by single doses of X-rays in the range of 0.5-8.0 Gy

Superovulation and embryo recovery in Boer goats treated with ...

African Journals Online (AJOL)

Lehloenya

Keywords: Boer goats, superovulation, oestrous synchronisation, pFSH, ... oestrous detection was performed three times daily at 8 h intervals with the aid ... sheep, where FSH/GnRHa treated ewes recorded a significant higher ... following short term storage of bovine IVP blastocysts at 25 ºC in EmcareTM compared to ovum.

Estrogen receptor alpha localization in the testes of men with normal spermatogenesis Estrogen receptor alpha localization in the testes of men with normal spermatogenesis

OpenAIRE

Eliza Filipiak; Dagmara Suliborska; Maria Laszczynska; Renata Walczak-Jedrzejowska; Elzbieta Oszukowska; Katarzyna Marchlewska; Krzysztof Kula; Jolanta Slowikowska-Hilczer

2012-01-01

It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER) a and
b. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate
the localization of ERa in the testes of adult men with normal spermatogenesis. Semen analysis of ten adult men
revealed azoospermia. FSH, LH and testosterone serum concentrations were within normal values, and the volume
of the te...

G protein-coupled receptor mutations and human genetic disease.

Science.gov (United States)

Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

2014-01-01

Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

Expression pattern of G protein‑coupled estrogen receptor 1 (GPER) in human cumulus granulosa cells (CGCs) of patients with PCOS.

Science.gov (United States)

Zang, Lili; Zhang, Quan; Zhou, Yi; Zhao, Yan; Lu, Linlin; Jiang, Zhou; Peng, Zhen; Zou, Shuhua

2016-06-01

Estradiol mediates its actions by binding to classical nuclear receptors, estrogen receptor α (ER-α) and estrogen receptor β (ER-β), and the non-classical G protein-coupled estrogen receptor 1(GPER). Several gene knockdown models have shown the importance of the receptors for growth of the oocyte and for ovulation. The aim of our study was to identify the pattern of GPER expression in human cumulus granulosa cells (CGCs) from ovarian follicles at different stages of oocyte maturation, and the differences of GPER expression between polycystic ovary syndrome (PCOS) patients and non-PCOS women. Thirty-eight cases of PCOS patients and a control group of thirty-two infertile women without PCOS were used in this study. GPER's location in CGCs was investigated by immunohistochemistry. Quantitative RT-PCR and western blot were used to identify the quantify GPER expression. Here we demonstrated that GPER was expressed in CGCs of both PCOS patients and non-PCOS women, and the expression of GPER was decreased significantly during oocyte maturation. But the expression levels of GPER in CGCs of PCOS patients and non-PCOS women were not significantly different. The data indicate that GPER may play a role during human oocyte maturation through its action in cumulus granulosa cells. AMHRIIs: anti-Mullerian hormone type II receptors; BMI: body mass index; CGCs: cumulus granulosa cells; COH: controlled ovarian hyperstimulation; E2: estradiol; EGFR: epidermal growth factor receptor; ER-α: estrogen receptor; ER-β: estrogen receptor β; FF: follicular fluid; FSH: follicle-stimulating hormone; GCs: granulosa cells; GPER: G protein-coupled estrogen receptor 1; GV: germinal vesicle; GVBD: germinal vesicle breakdown; HCG: human chorionic gonadotropin; IRS: immunoreactive score; IVF-ET: in vitro fertilization and embryo transfer; MI: metaphase I; MII: metaphase II; MAPK: mitogen-activated protein kinase; OCCCs: oocyte corona cumulus complexes; PCOS: polycystic ovarian syndrome; q

Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

Science.gov (United States)

Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

2009-11-01

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

Potency determination of follitropin, lutropin And thyrotropin: a comparison between the quantification by reversed-phase high-performance liquid chromatography and in vivo bioassay; Determinacao de potencia de diferentes preparacoes de foliculotrofina, luteotrofina e tireotrofina: comparacao entre a quantificacao por cromatografia liquida em fase reversa e por bioensaio in vivo

Energy Technology Data Exchange (ETDEWEB)

Almeida, Beatriz Elane de

2013-07-01

With the intention of setting up physico-chemical methods as an alternative to in vivo bioassay for determining biological activity, the hFSH, hTSH and hLH content of native and recombinant preparations was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and compared with the data obtained by the classical mouse or rat in vivo bioassays (BA). A linear relationship between the two methods was found for these hormones: hFSH BA{sub U=} 0.9925 RP-HPLC{sub U–} 1.3165, r = 0.9371, p < 0.001, n = 24; hTSH BAμg = 0.9790 RP-HPLCμg - 0.052, r = 0.8725, p < 0.001, n = 14; hLH BA{sub IU} = 0.8771 RP-HPLC{sub IU} + 12.41, r = 0.9786, p < 0.01, n = 5. For nine other hFSH and eleven hTSH preparations, the mean difference ( ) between the bioactivity predicted from RP-HPLC data via these equations and the mean of the bioactivities obtained with the two methods was as follows. For hLH this difference could not be estimated due to lack of different samples. In the case of hFSH, ± SD = -2.11 ± 3.49% with a precision of 1.16% and in the case of hTSH, ± SD = -2.01 ± 5.56 %, with precision of 1.68%. Partly-degraded hFSH, hTSH and hLH samples presented different activity degrees that could be predicted by RP-HPLC, with an acceptable agreement with the in vivo bioassays. These results demonstrate that the employment of a non-animal physico-chemical assay, such as RP-HPLC, is a viable alternative to the use of an in vivo bioassay for hFSH and hTSH potency determination, thus reducing the number of animals currently used for assuring quality and efficacy of a pharmaceutical product. (author)

Antidopaminergic-induced hypothalamic LHRH release and pituitary gonadotrophin secretion in 12 day-old female and male rats.

Science.gov (United States)

Lacau-Mengido, I M; Becú-Villalobos, D; Thyssen, S M; Rey, E B; Lux-Lantos, V A; Libertun, C

1993-12-01

In previous studies we have shown that the developing rat provides an interesting physiologic model in which the dopaminergic control of both LH and FSH is well defined in contrast to the controversial results obtained in adult rats. We wished to establish the role of testosterone in antidopaminergic induced gonadotrophins release in 12 day-old male and female rats, and evaluate the effect of antidopaminergic drugs at the hypothalamic level during this developmental stage. Haloperidol, an antidopaminergic drug, increased both LH and FSH in female 12 day-old rats but not in male littermates. The effect was blocked by bromocriptine and not by phentolamine indicating that haloperidol acted on the dopaminergic receptor, and that unspecific stimulation of the noradrenergic system was not involved. Haloperidol was ineffective when female rats were previously ovariectomized and injected with testosterone propionate at 9 days of age. If females were treated on the day of birth with testosterone propionate, haloperidol-induced FSH and LH release was also abolished. In control males haloperidol had no effect on the release of LH or FSH. But if males were orchidectomized at birth or at 9 days of age, haloperidol released both LH and FSH during the infantile period. In an attempt to establish the site of action of antidopaminergic drugs on gonadotrophin release, hypothalami (mediobasal and preoptic-suprachiasmatic area) from 12 day-old infant female rats were perifused with either haloperidol or domperidone (2*10(-6) M). Both drugs increased LHRH release into the perifusate. Besides haloperidol did not modify the release of LH or FSH from adenohypophyseal cells incubated in vitro. We therefore conclude that antidopaminergic-induced gonadotrophins release is modulated by serum testosterone concentrations, and that the site of action is probably the LHRH-secreting neuron of the hypothalamus.

Potency determination of follitropin, lutropin And thyrotropin: a comparison between the quantification by reversed-phase high-performance liquid chromatography and in vivo bioassay

International Nuclear Information System (INIS)

Almeida, Beatriz Elane de

2013-01-01

With the intention of setting up physico-chemical methods as an alternative to in vivo bioassay for determining biological activity, the hFSH, hTSH and hLH content of native and recombinant preparations was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and compared with the data obtained by the classical mouse or rat in vivo bioassays (BA). A linear relationship between the two methods was found for these hormones: hFSH BA U= 0.9925 RP-HPLC U– 1.3165, r = 0.9371, p IU = 0.8771 RP-HPLC IU + 12.41, r = 0.9786, p < 0.01, n = 5. For nine other hFSH and eleven hTSH preparations, the mean difference ( ) between the bioactivity predicted from RP-HPLC data via these equations and the mean of the bioactivities obtained with the two methods was as follows. For hLH this difference could not be estimated due to lack of different samples. In the case of hFSH, ± SD = -2.11 ± 3.49% with a precision of 1.16% and in the case of hTSH, ± SD = -2.01 ± 5.56 %, with precision of 1.68%. Partly-degraded hFSH, hTSH and hLH samples presented different activity degrees that could be predicted by RP-HPLC, with an acceptable agreement with the in vivo bioassays. These results demonstrate that the employment of a non-animal physico-chemical assay, such as RP-HPLC, is a viable alternative to the use of an in vivo bioassay for hFSH and hTSH potency determination, thus reducing the number of animals currently used for assuring quality and efficacy of a pharmaceutical product. (author)

Penggunaan Follicle Stimulating Hormone dan Pregnant Mare Serum Gonadotrophin untuk Superovulasi pada Sapi Persilangan Brahman

Directory of Open Access Journals (Sweden)

Adrian

2009-12-01

Full Text Available Twenty cattle were used in this experiment to determine the effect of administration follicle stimulating hormone (FSH and pregnant mare serum gonadotrophin (PMSG hormones on superovulation of Brahman cross cattle. The experiment was designed into completely randomized design with 5 treatments as follows. Treatments 1 (T1: 4 mg of FSH was injected twice a day intra-ovary, T2: 8 mg of FSH was injected twice a day intra-ovary, T3: 300 IU of PMSG was injected single dose intra-ovary, T4: 600 IU of PMSG was injected single dose intra-ovary, T5: 40 mg of FSH was injected intramuscular. All experimental cattle were oestrus synchronized using 15 mg of PGF2α twice at 11-days intervals. Number of corpus luteum (CL was detected by rectal palpation at day-7 after artificial insemination. Results showed that 19 cattle (95% indicated oestrus sign. Eleven cattle (57.9% showed oestrus sign 2 days after PGF2α injection and the rest 8 cattle (42.1% oestrus sign was detected at 3 days after PGF2α injection. FSH and PMSG treatments increased significantly (P<0.05 number of CL. The highest CL number was found in T5, meanwhile number of CL in T2 and T4 were higher compared to T1 and T3. The average treatment effect could produce 6.8±5.42 CL with range 2–26 CL. On the other hand single dose treatment of 600 IU PMSG (T4 showed high significant number of non ovulatory (persistent follicle compared to other treatments (T1, T2, T3 and T5 on average number of persistent follicle 2.0±1.97 from 19 cattles. It is concluded that the best superovulation treatment was produced by injection 40 mg of FSH intra-musculary.

The efficiency of in vitro ovine embryo production using an undefined or a defined maturation medium is determined by the source of the oocyte.

Science.gov (United States)

Cocero, M J; Alabart, J L; Hammami, S; Martí, J I; Lahoz, B; Sánchez, P; Echegoyen, E; Beckers, J F; Folch, J

2011-06-01

In vitro oocyte maturation can be influenced by oocyte source and maturation media composition. The aim of the present study was to compare the efficiency of a defined in vitro maturation medium (TCM199 supplemented with cysteamine and epidermal growth factor; Cys + EGF) with an undefined medium (TCM199 supplemented with follicle-stimulating hormone and follicular fluid; FSH + FF) for in vitro production (IVP) of ovine embryos, using oocytes obtained by laparoscopic ovum pick-up from FSH-stimulated [n=11; 158 cumulus-oocyte complexes (COCs)] and non-stimulated (n=16; 120 COCs) live ewes, as well as abattoir-derived oocytes (170 COCs). The produced blastocysts were vitrified and some of them were transferred to synchronized recipients. The best and the worst final yields of embryo IVP observed in this study were obtained using oocytes from FSH-stimulated ewes matured in FSH + FF (41.3%; 33/80) and in Cys + EGF (19.2%; 15/78) medium, respectively (p<0.01). No significant differences between both media were attained in the blastocyst development rate or in the final yield of embryo IVP using oocytes from non-stimulated ewes or abattoir-derived oocytes. The overall in vivo survival rate of the transferred vitrified blastocysts was 13.1% (8/61), without significant differences between oocyte sources or maturation media. In conclusion, under the experimental conditions of the present study, TCM199 supplemented with cysteamine and EGF is a convenient defined maturation medium for IVP of embryos from oocytes of live non-stimulated ewes or from oocytes of abattoir-derived ovaries. However, the best final yield of embryo IVP observed in this study was attained when oocytes came from FSH-stimulated donors and TCM199 was supplemented with FSH and follicular fluid. © 2010 Blackwell Verlag GmbH.

Regulation of follitropin-sensitive adenylate cyclase by stimulatory and inhibitory forms of the guanine nucleotide regulatory protein in immature rat Sertoli cells

International Nuclear Information System (INIS)

Johnson, G.P.

1987-01-01

Studies have been designed to examine the role of guanine nucleotides in mediating FSH-sensitive adenylate cyclase activity in Sertoli cell plasma membranes. Analysis of [ 3 H]GDP binding to plasma membranes suggested a single high affinity site with a K d = 0.24 uM. Competition studies indicated that GTP γ S was 7-fold more potent than GDP β S. Bound GDP could be released by FSH in the presence of GTP γ S, but not by FSH alone. Adenylate cyclase activity was enhanced 5-fold by FSH in the presence of GTP. Addition of GDP β S to the activated enzyme (FSH plus GTP) resulted in a time-dependent decay to basal activity within 20 sec. GDP β S competitively inhibited GTP γ S-stimulated adenylate cyclase activity with a K i = 0.18 uM. Adenylate cyclase activity was also demonstrated to be sensitive to the nucleotide bound state. In the presence of FSH, only the GTP γ S-bound form persisted even if GDP β S previously occupied all available binding sites. Two membrane proteins, M r = 43,000 and 48,000, were ADP·ribosylated using cholera toxin and labeling was enhanced 2 to 4-fold by GTP γ S but not by GDP β S. The M r = 43,000 and 48,000 proteins represented variant forms of G S . A single protein of M r = 40,000 (G i ) was ADP-ribosylated by pertussis toxin in vitro. GTP inhibited forskolin-stimulated adenylate cyclase activity with an IC 50 = 0.1 uM. The adenosine analog, N 6 ·phenylisopropyl adenosine enhanced GTP inhibition of forskolin-stimulated adenylate cyclase activity by an additional 15%. GTP-dependent inhibition of forskolin-sensitive adenylate cyclase activity was abolished in membranes prepared from Sertoli cells treated in culture with pertussis toxin

Toward developing recombinant gonadotropin-based hormone therapies for increasing fertility in the flatfish Senegalese sole.

Directory of Open Access Journals (Sweden)

François Chauvigné

Full Text Available Captive flatfishes, such as the Senegalese sole, typically produce very low volumes of sperm. This situation is particularly prevalent in the first generation (F1 of reared sole males, which limits the development of artificial fertilization methods and the implementation of selective breeding programs. In this study, we investigated whether combined treatments with homologous recombinant follicle-stimulating (rFsh and luteinizing (rLh hormones, produced in a mammalian host system, could stimulate spermatogenesis and enhance sperm production in Senegalese sole F1 males. In an initial autumn/winter experiment, weekly intramuscular injections with increasing doses of rFsh over 9 weeks resulted in the stimulation of gonad weight, androgen release, germ cell proliferation and entry into meiosis, and the expression of different spermatogenesis-related genes, whereas a subsequent single rLh injection potentiated spermatozoa differentiation. In a second late winter/spring trial corresponding to the sole's natural prespawning and spawning periods, we tested the effect of repeated rLh injections on the amount and quality of sperm produced by males previously treated with rFsh for 4, 6, 8 or 10 weeks. These latter results showed that the combination of rFsh and rLh treatments could increase sperm production up to 7 times, and slightly improve the motility of the spermatozoa, although a high variability in the response was found. However, sustained administration of rFsh during spawning markedly diminished Leydig cell survival and the steroidogenic potential of the testis. These data suggest that in vivo application of rFsh and rLh is effective at stimulating spermatogenesis and sperm production in Senegalese sole F1 males, setting the basis for the future establishment of recombinant gonadotropin-based hormone therapies to ameliorate reproductive dysfunctions of this species.

Inhibin A and B in adolescents and young adults with Turner's syndrome and no sign of spontaneous puberty

DEFF Research Database (Denmark)

Gravholt, C.H.; Næraa, R.W.; Andersson, A.M.

2002-01-01

The aim of this study was to assess levels of inhibin A and B, FSH and LH in Turner's syndrome (TS) without signs of spontaneous ovarian activity.......The aim of this study was to assess levels of inhibin A and B, FSH and LH in Turner's syndrome (TS) without signs of spontaneous ovarian activity....

Modificações dos níveis de gonadotrofinas durante a vida reprodutiva Gonadotropin level changes during the reproductive life

Directory of Open Access Journals (Sweden)

Sebastião Freitas de Medeiros

2007-01-01

Full Text Available As modificações nas concentrações das gonadotrofinas ao longo da vida reprodutiva dependem de amadurecimento funcional harmônico entre conexões neurais, neurônios-GnRH no hipotálamo, gonadotropos hipofisários e células da granulosa e teca da parede folicular. As concentrações de LH e FSH sofrem variações com o período do dia, fase do ciclo menstrual e idades ginecológica e cronológica. A variação circadiana é marcante para o LH e ocorre na fase puberal, quando os pulsos têm maior freqüência e amplitude no período noturno. Na fase puberal tardia, os pulsos das gonadotrofinas ocorrem também durante o dia e perdem a variação noite-dia, permanecendo discretas alterações durante as 24 horas do dia. No ciclo menstrual, durante os anos reprodutivos, o FSH eleva-se no final da fase lútea tardia, declina na fase folicular média, eleva-se bruscamente na fase ovulatória e permanece em níveis basais até a fase lútea tardia. O LH permanece em níveis constantes durante toda a fase folicular, eleva-se no pico ovulatório e declina a níveis basais na fase lútea. Na quarta década, há modificações hipotálamo-neurais na secreção de GnRH, atenuação do retrocontrole positivo exercido pelo estradiol e diminuição na freqüência e prolongamento dos pulsos de GnRH. A hipófise responde com diminuição na densidade de receptores-GnRH, perda da sensibilidade do gonadotropo, secreção de gonadotrofinas mais básicas com maior meia-vida, diminuição na freqüência e maior amplitude dos pulsos de LH e FSH e secreção preferencial de FSH. Estas modificações, associadas à aceleração no consumo folicular, explicam a elevação monotrópica mais rápida de FSH após os 37-38 anos e a manutenção de níveis quase constantes de LH até o final do período reprodutivo. Estudos consistentes mostram que a elevação seletiva dos níveis basais de FSH na fase folicular precoce na verdade é gradual, sendo observada já na

Changes of endocrine and ultrasound markers as ovarian aging in modifying the Stages of Reproductive Aging Workshop (STRAW) staging system with subclassification of mid reproductive age stage.

Science.gov (United States)

Ding, Ting; Luo, Aiyue; Jiang, Jingjing; Du, Xiaofang; Yang, Shuhong; Lai, Zhiwen; Shen, Wei; Lu, Yunping; Ma, Ding; Wang, Shixuan

2013-01-01

To demonstrate the changes of ovarian aging markers across the Stages of Reproductive Aging Workshop (STRAW) stages and modify it with subclassification of mid reproductive age stage (MR). Healthy females were classified according to the STRAW system. Serum basal FSH, LH, E2, and anti-Müllerian hormone (AMH) were detected, FSH/LH ratio calculated, and antral follicle counts (AFCs) determined in follicular phase. Progression through the whole STRAW stages under MR stage subdivided is associated with elevations in FSH, LH, FSH/LH ratio and decreases in E2, AMH and AFCs (p age in MR stage. 0.982 ng/ml AMH and 3 antral follicles (low level of MR 25-30 years) were set as cutoffs to distinguish MR stage into early mid reproductive age (EMR) and late mid reproductive age (LMR) stages. The women in EMR stage compared with LMR could retrieve more oocytes in IVF treatment (p stage, demonstrating disparate reproductive aging period with reduced ovarian reserve in young age across the STRAW stages.

Post-treatment fertility in patients with testicular cancer

International Nuclear Information System (INIS)

Fossaa, S.D.; Aabyholm, T.; Normann, N.; Jetne, V.

1986-01-01

Sperm analysis and serum hormone measurements (LH, FSH, testosterone) were performed in 29 patients after orchiectomy for seminoma before and after irradiation. Before radiotherapy 14 of 20 orchiectomised patients were azoospermic or had impaired spermatogenesis. A minimum sperm count was found 1 year after radiotherapy with gradual improvement up to 2 years. The recovery of sperm cell production was impaired most in patients with pre-treatment sperm counts < 3 million/ ml. Serum testosterone remained at low normal levels throughout the observation period. The mean serum FSH was increased 1 year after radiotherapy but returned to normal in 50% of patients within 3 years after treatment. This post-treatment increase in FSH was significantly correlated with increased pre-treatment FSH but not with the gonadal dose, which was 1 to 3% of the target dose. Severe disturbances in spermatogenesis, observed 2 to 3 years after radiotherapy for early seminoma, are likely to be the expression of a highly impaired pre-treatment sperm cell production and only to a lesser degree dependent on the irradiation of the remaining testicle. (author)

Effect of altering the intervals between consecutive superovulatory doses of porcine follicle-stimulating hormone on ovarian responses and embryo yields in anestrous ewes.

Science.gov (United States)

Bartlewski, P M; Murawski, M; Schwarz, T; Oliveira, M E F

2017-05-01

The effect of varying intervals between successive gonadotropin injections on the superovulatory outcomes in anestrous Rideau Arcott ewes superstimulated for ovarian follicular development with multiple doses of porcine FSH (pFSH) was evaluated in a single study. Twenty-five animals received six (1×2.5ml and 5×1.25ml) injections of Folltropin ® -V given at 0800 and 1600h or at 0800 and 2000h in Group 1 (n=9) or Group 2 (n=16), respectively. An i.m. injection of 500 IU of equine chorionic gonadotropin (eCG; Folligon ® ) was given concurrently with the first pFSH dose. Time of estrus was synchronized among ewes with intravaginal sponges containing 60mg of medroxyprogesterone acetate (Veramix ® ) that were left in place for 14days; sponges were removed at the time of the 5th pFSH injection. Six days after insertion of MAP sponges, all ewes received an i.m. injection of estradiol-17β dissolved in 1ml of sesame oil (350μg/ewe) to synchronize follicular wave emergence. Following the last pFSH dose, all animals were given a single i.m. injection of 50μg of gonadotropin-releasing hormone (GnRH; Cystorelin ® ) to induce ovulations before placing in a pen with four fertile rams for 36h. The ovarian responses were assessed and embryos recovered surgically 7days after GnRH injections. The mean number of corpora lutea was greater (Pewes (21.0±2.9 compared with 10.4±1.6, respectively; mean±SEM) but there was no difference (P>0.05) in the number of transferable embryos (5.4±2.4 compared with 5.4±1.3/ewe, respectively), and Group 1 animals had significantly more degenerated embryos than Group 2 ewes (2.6±1.2 compared with 0.6±0.3/ewe, respectively). A superovulatory protocol wherein pFSH injections were given at 0800 and 1600h was more effective in terms of inducing multiple ovulations than the protocol with 12-h intervals between consecutive pFSH doses, but it was not associated with an increased production of transferable quality embryos by anestrous ewes

Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins.

Science.gov (United States)

Nahuis, M J; Kose, N; Bayram, N; van Dessel, H J H M; Braat, D D M; Hamilton, C J C M; Hompes, P G A; Bossuyt, P M; Mol, B W J; van der Veen, F; van Wely, M

2011-07-01

Long-term effects of laparoscopic electrocautery of the ovaries are unknown. To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins, we followed women with clomiphene-resistant polycystic ovary syndrome (PCOS) randomly allocated to one of these treatments until 8-12 years after their initial treatment. Between February 1998 and October 2001 168 women with clomiphene citrate-resistant PCOS were included in a randomized controlled trial comparing an electrocautery strategy to a strategy starting with rFSH. In 2009 these women were contacted about their reproductive outcome and menstrual cycle regularity. Analysis was by intention-to-treat. We compared time to conception resulting in live birth, subsequent pregnancies, ectopic and multiple pregnancies, menopause, as well as minimal and maximal menstrual cycle length. After 8-12 years, the cumulative proportion of women with a first child was 86% in women who had been allocated to electrocautery versus 81% in women who had been allocated to immediate rFSH [relative ratio (RR): 1.1; 95% confidence interval (CI): 0.92-1.2]. Treatment with electrocautery resulted in a significantly lower need for stimulated cycles to reach a live birth; 53% after electrocautery versus 76% after rFSH (RR: 0.69; 95% CI: 0.55-0.88).The cumulative proportion of women with a second child was 61% after electrocautery versus 46% after immediate rFSH (RR: 1.4; 95% CI: 1.00-1.9). Overall, there were 7 twins out of 134 deliveries (5%) after electrocautery versus 10 twins out of 124 deliveries (8%) in the rFSH group (RR: 0.65; 95% CI: 0.25-1.6). Fifty-four per cent of the women allocated to electrocautery had a regular menstrual cycle 8-12 years after randomization versus 36% in those allocated to rFSH (RR: 1.5; 95% CI: 0.87-2.6). In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries is as effective as ovulation induction with FSH treatment in terms of live births, but reduces

Effect of administration of vitamins C and E on fertilization capacity of rats exposed to noise stress

Directory of Open Access Journals (Sweden)

Ghasem Saki

2013-01-01

Full Text Available The aims of this study were to evaluate the effects of administration of Vitamins C and E on fertilization capacity in rats exposed to noise stress. 40 adult male rats were randomly divided into 5 equal groups. Group 1 as controls who were not exposed to noise and groups 2-5 exposed to noise with 90-120 dB intensity and 300-350 Hz frequency from 7 pm to 7 am everyday for 50 days. Group 2 exposed to noise and did not receive Vitamins. Group 3 received vitamin C, Group 4 received Vitamin E. Group 5 received Vitamins C and E concomitantly. After 50 days, serum Follicle-stimulating hormone (FSH, Luteinizing hormone (LH and testosterone were calculated. Then each rat was left with three female rats for mating. Pregnant females were sacrificed on the 19 th day of pregnancy and evaluated for the presence and number of viable, dead and absorbed fetuses. The level of FSH, LH and testosterone significantly decreased in rats exposed to noise (P < 0.05. By administration of Vitamins in groups 3-5 we observed that the level of hormones significantly increased in compared to group 2 (P < 0.05. The fertilization capacity of male rats in groups 3-5 significantly increased in compared to group 2 (P < 0.05. There was significant difference between groups 1 and 2 in case of fertilization capacity (P = 0.001. The data in this study strongly suggests a negative role for noise stress on level of FSH, LH and testosterone level and also fertilization capacity of male rats. To complement the information it is suggested that this research be done on human samples.

Development of radioimmunoassay techniques for measurement of gonadotrophins and other hormones with application in pharmacological studies of the anterior hypophysis in man. Part of a coordinated programme on in vitro assay techniques. Final report for the period 1 September 1972--30 September 1975

Energy Technology Data Exchange (ETDEWEB)

Simionescu, L

1975-01-01

Human studies were performed on psychiatric patients, patients under thyroidectolmy stress and normal individuals. Radioimmunoassay determined HGH, insulin, LH, FSH and testosterone in basal condition in psychiatric patients and in normal subjects. The same hormones were also measured in untreated psychiatric patients during and acute administration of chlorpromazine (CPZ). Changes in insulin, LH, FSH and testosterone remained within the limits of variation generally observed in or between individuals. The HGH level was increased paradoxically after CPZ administration in some parapsychiatric untreated patients. Constant increase in prolactin was observed both in chronic treated patients and during acute administration of CPZ. Measuring HGH, insulin, LH, FSH or testosterone during acute administration of CPZ does not appear to be relevant model for studying the influence of this drug on hormone release. The release of GH during thyroidectomy for hyperthyroidia proved similar to release during general surgery, while release of prolactin is lower. The reasons for this are discussed. Radioimmunoassay gave data on GH in infants, children and adolescents. Measurement of GH levels during an acute test (insulin and glucagon) allowed classification of hypostatural children into ''pituitary dwarfism'', ''non-pituitary dwarfism'' and ''limited response dwarfism''. A doubling of LH levels appeared at the 13-14 year age interval for both sexes. The hypophyseal and serum TSH was investigated in male adult rats exposed to cold, under immobilization stress or receiving substances acting as chemical suppressors (methyliouracyls) or neurotropic substances. The variations were classified in the percentual and multiplicative area in animals receiving neurotropic substances or exposed to metabolic sollicitations. The TSH determined by radioimmunoassay are evidence for the hypophysis-thyroidal feedback. The preparation of anti-testosterone sera and anti-HGH sera is described.

Comparison of fall prediction by the Hessisch Oldendorf Fall Risk Scale and the Fall Risk Scale by Huhn in neurological rehabilitation: an observational study.

Science.gov (United States)

Hermann, Olena; Schmidt, Simone B; Boltzmann, Melanie; Rollnik, Jens D

2018-05-01

To calculate scale performance of the newly developed Hessisch Oldendorf Fall Risk Scale (HOSS) for classifying fallers and non-fallers in comparison with the Risk of Falling Scale by Huhn (FSH), a frequently used assessment tool. A prospective observational trail was conducted. The study was performed in a large specialized neurological rehabilitation facility. The study population ( n = 690) included neurological and neurosurgery patients during neurological rehabilitation with varying levels of disability. Around the half of the study patients were independent and dependent in the activities of daily living (ADL), respectively. Fall risk of each patient was assessed by HOSS and FSH within the first seven days after admission. Event of fall during rehabilitation was compared with HOSS and FSH scores as well as the according fall risk. Scale performance including sensitivity and specificity was calculated for both scales. A total of 107 (15.5%) patients experienced at least one fall. In general, fallers were characterized by an older age, a prolonged length of stay, and a lower Barthel Index (higher dependence in the ADL) on admission than non-fallers. The verification of fall prediction for both scales showed a sensitivity of 83% and a specificity of 64% for the HOSS scale, and a sensitivity of 98% with a specificity of 12% for the FSH scale, respectively. The HOSS shows an adequate sensitivity, a higher specificity and therefore a better scale performance than the FSH. Thus, the HOSS might be superior to existing assessments.

Assessing The Impact Of Cancer Therapies On Ovarian Reserve

Science.gov (United States)

Gracia, Clarisa R.; Sammel, Mary D.; Freeman, Ellen; Prewitt, Maureen; Carlson, Claire; Ray, Anushree; Vance, Ashley; Ginsberg, Jill P.

2013-01-01

Objective To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared to healthy controls of similar age and late-reproductive age. Design Cross-sectional analysis of data from a prospective cohort study Setting University Medical Center Patients 71 cancer survivors age 15-39; 67 healthy, similarly aged unexposed subjects; 69 regularly menstruating women of late-reproductive age (40-52 years). Interventions: None Main Outcome measures Early follicular phase hormones (FSH, Estradiol, Inhibin B, AMH) and ovarian ultrasound measurements (ovarian volume and Antral Follicle Counts) were compared using multivariable linear regression. Results In adjusted models, FSH, AMH and AFC differed between exposed vs. unexposed (FSH 11.12mIU/ml vs. 7.25mIU/ml, p=0.001; AMH 0.81ng/ml vs. 2.85ng/ml, pscore was associated with increased levels of FSH (p= 0.016) and decreased levels of AMH (p=0.003). Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC and ovarian volume. AMH was similar in women previously exposed to high-dose cancer therapy and 40-42 year old controls. Conclusions Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared to unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to late-reproductive women. The predictive value of measures for pregnancy and menopause must be studied. PMID:22137491

Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep.

Science.gov (United States)

Manikkam, Mohan; Thompson, Robert C; Herkimer, Carol; Welch, Kathleen B; Flak, Jonathan; Karsch, Fred J; Padmanabhan, Vasantha

2008-04-01

The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH) secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol (E2) receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis. We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release. Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release.

Interleukin 1α inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

International Nuclear Information System (INIS)

Rettori, V.; McCann, S.M.; Gimeno, M.F.; Karara, A.; Gonzalez, M.C.

1991-01-01

Interleukin 1α (IL-1α), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1α into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1α caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1α (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E 2 into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1α reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1α suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E 2 -mediated release of LHRH

Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

Science.gov (United States)

Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

2014-02-01

Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side

Radiations - induced disorders in ovarian function

International Nuclear Information System (INIS)

Saleh, S.; Roushdy, H.M.; Abdel-Aziz, M.T.; Eldenshary, A.E.; Abdel-Khalek, A.; Ramadan, L.A.

1988-01-01

The effect of whole body gamma radiation exposure (7.5 and 6.5 Gy) on the secretory activity and the structure of the ovaries was investigated. The parameters studied were serum levels of oestrogen, progesterone, Lh and FSH, beside histopathological studies of the ovaries of femaler rats. These were measured on the next day after radiation exposure and then after one two oestrus cycles. Whole body gamma - irradiation of females rats at two levels of exposure progressively decreased the level of oestrogen and progesterone while increased the level of LH and FSH as compared with the control. moreover, the changes in the ovaries were demonstrated in the histopathological investigation. Keywords: Radiation exposure - ovarian function - hormone radioimmunoassay - oestrogen - progesterone - LH - FSH

Detection of leptin in serum from patients with polycystic ovary syndrome

International Nuclear Information System (INIS)

Chu Yongli; Sun Yongyu; Qiu Hongyu

2002-01-01

Objective: To investigate the relationship between leptin and insulin resistance in polycystic ovary syndrome (PCOS). Methods: Blood samples for leptin, LH/FSH, fasting insulin and glucose measurement from 17 patients with PCOS and 20 cases as control group were analyzed by radioimmunoassay or oxidase test. Results: It showed that leptin, LH/FSH levels of serum, insulin resistant index (IRI) and body mass index (BMI) in patients with PCOS were significantly higher than that in the control group (P<0.05). Leptin level was positively related with IRI and LH/FSH and BMI (P<0.01, P<0.05, P<0.01). Conclusion: It was suspected that leptin accelerate insulin resistance, the interaction of two factors aggravate the change of pathophysiology in PCOS

Ganirelix for luteolysis in poor responder patients undergoing IVF treatment: a Scandinavian multicenter 'extended pilot study'

DEFF Research Database (Denmark)

Nilsson, Lena; Andersen, A.N.; Lindenberg, Svend

2010-01-01

To enhance oocyte yield and pregnancy outcome in poor responder women undergoing IVF treatment, daily low dose GnRH antagonist administration was given during the late luteal phase to induce luteolysis and possibly secure a more synchronous cohort of recruitable follicles. An open extended pilot...... study in four Scandinavian fertility centers was done including 60 patients. Poor response was defined as when 2000 IU FSH. GnRH antagonist (ganirelix) was given, 0.25 mg s.c. daily, from days 3 to 5...... oocyte retrievals resulting in 5 pregnancies (4 delivered). Despite GnRH antagonist administration in the late luteal phase and menstrual bleeding, FSH was not sufficiently reduced to secure a more synchronic cohort of recruitable follicles. Novel GnRH antagonists more specifically targeting FSH release...

Effects of pelvic telecobalt irradiation on gonadotropin secretin

International Nuclear Information System (INIS)

Pfenninger, R.

1978-01-01

The pitnitary reaction in women operated according to Wertheim who had menstruated regularly was investigated during telecobalt irradiation. The pitnitary reaction was observed with the aid of the gonadotropin releasing factor. A dose of 25 mcg RH-LH was applied. Releasing factor examinations were carried out before exposure with functioning ovaries, after a dose of 2000 R (i.e., after 10 exposures), and after 6000 R. In the meantime, separate gonadotropin examinations were carried out continuously. A FSH reaction was observed already after 14 days, and the values were raised to almost menopause values. After this, the FSH increased further, while the LH reaction was not observed until much later. The investigation suggests an interrelation between follicle apparatus and FSH, oestrogens and LH. (orig./AJ) [de

In-vitro secretion of inhibin-like activity by Sertoli cells from normal and prenatally irradiated immature rats

International Nuclear Information System (INIS)

Ultee-van Gessel, A.M.; Leemborg, F.G.; Jong, F.H. de; Molen, H.J. van der

1986-01-01

The influence of in-vitro conditions on the production of inhibin by Sertoli cells from 21-day-old normal and prenatally irradiated rat testes was studied by measuring inhibin activity in culture media, using the suppression of the release of FSH from cultured rat pituitary cells. Sertoli cells secreted inhibin-like activity during at least 21 days of culture, and cells cultured at 37 0 C produced significantly more inhibin than those cultured at 32 0 C. The presence of fetal calf serum had no significant effect on inhibin production at 32 0 C, while at 37 0 C the production was decreased. The presence of ovine FSH stimulated inhibin secretion, while inhibin concentrations in Sertoli cell culture media were decreased after the addition of testosterone. Testosterone, added together with ovine FSH, suppressed inhibin secretion when compared with the levels found in the presence of FSH alone. The presence of spermatogenic cells decreased the release of inhibin. From these results it was concluded that both Sertoli cells isolated from normal immature rat testes and those from testes without spermatogenic cells can secrete inhibin-like activity in culture. A number of discrepancies with in-vivo observations was observed. (author)

Analysis of the relationship between temporary or permanent amenorrhea and ovarian function after uterine artery embolization

International Nuclear Information System (INIS)

Cao Manrui; He Jianlong; Liu Bingguang; Teng Yan; Sun Lihong

2006-01-01

Objective: To analyze the cases of amenorrhea after uterine artery embolization (UAE) and to find out the relationship with ovarian dysfunction or failure. Methods: Ten cases out of 287 patients with uterus myoma who underwent UAE were found amenorrhea. Six of them had temporary and 4 had permanent amenorrhea (38, 47, 48 and 48 years old). Preprocedural and postprocedural menstruations, blood FSH levels correlative factors including surgical operations, were observed and analyzed. Results: Menstruations of 6 cases with temporary amenorrhea were completely recovered without any significant changes in blood FSH levels, while 4 permanent amenorrhea cases demonstrated significant differences in blood FSH levels after the procedure. Their blood FSH were all > 20 u /L after UAE with one of them > 100 u /L 24 months later and another 38 year-old patient underwent surgical operation of ovaries bilaterally before UAE. Conclusions: Temporary amenorrhea may not mean ovarian dysfunction or failure. The probability of ovarian dysfunction or failure after UAE is low, which mainly occur in the peirmenopausal patients. Consideration of the probability of inducing early ovarian failure, caution should be taken for UAE on the patients having ovarian surgery before. (authors)

Mucuna pruriens improves male fertility by its action on the hypothalamus-pituitary-gonadal axis.

Science.gov (United States)

Shukla, Kamla Kant; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem; Shankhwar, Satya Narain; Rajender, Singh; Jaiswar, Shyam Pyari

2009-12-01

To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility. Prospective study. Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India. Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening. High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL. Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured. Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment. Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.

The combined effects of pituitary gonadotropin and estrogen on the ovarian response of rats to /sup 125/I-LH uptake

Energy Technology Data Exchange (ETDEWEB)

Hosomichi, T; Yoshida, H; Ichinohe, K [Wakayama Medical Coll. (Japan)

1974-12-01

It discussed the effect of estradiol on the ovarian response of mature rats and hypophysectomized mature rats to /sup 125/I-LH uptake and the combined effects of FSH and estradiol. The constant concentration on the change of blood concentration with time was maintained in about one hour when given with the intravenous infusion of /sup 125/I-LH prepared for radioimmunoassay. Moreover, increased uptake of /sup 125/I-LH was noted especially in ovaries, livers, kidneys and thyroid glands, and by giving estradiol the uptake was increased to a level which was about twice the normal. Of hypophysectomized rats, the uptake was increased to a level which was about four times the normal in the group of rats which were given estradiol for eight days and also in the group of rats which were given FSH for four days. The effect with four-day-estradiol administration following four-day-FSH administration was to increase to a level which was about six times the group which was given each single administration. These experimental results are apparently due to the effects of FSH and estradiol on follicles and thus follicles are ready for LH uptake.

Influence of large testicular dose on neuroendocrine function in rats

International Nuclear Information System (INIS)

Gong Shouliang; Liu Shuzheng

1992-01-01

In present study, the changes of hypothalamic endogenous opiate peptides and the endocrine function of pituitary and testes were observed at 1, 23, 63 and 97 days after exposure of testes to 10 Gy X-rays in male Wistar rats to attempt to clarify the neuroendocrine effect of ionizing radiation and its mechanism. One day after irradiation, hypothalamic β-endorphin (β-EP) content increased significantly, but serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (TS) and cAMP content in tests were lowered in varying degrees. Twenty three days after irradiation, hypothalamic β-EP content decreased, while serum LH, FSH, TS and testicular cAMP content increased very significantly. Sixty three days after irradiation, the level of hypothalamic β-EP still was the same as that at 23 days after irradiation, hypothalamic leu-enkephalin (L-Enk) content decreased significantly, serum LH and FSH levels still continued to increase up, while serum TS and testicular cAMP contents declined very significantly. Ninety seven days after irradiation, serum LH and FSH levels returned to lower, serum TS and testicular cAMP content still continued to decrease, and in testicular tissue, serious lesion occurred

Enhanced Near-cloak by FSH Lining

OpenAIRE

Liu, Hongyu; Sun, Hongpeng

2011-01-01

We consider regularized approximate cloaking for the Helmholtz equation. Various cloaking schemes have been recently proposed and extensively investigated. The existing cloaking schemes in literature are (optimally) within $|\\ln\\rho|^{-1}$ in 2D and $\\rho$ in 3D of the perfect cloaking, where $\\rho$ denotes the regularization parameter. In this work, we develop a cloaking scheme with a well-designed lossy layer right outside the cloaked region that can produce significantly enhanced near-cloa...

Effect of different culture systems and 3, 5, 3'-triiodothyronine/follicle-stimulating hormone on preantral follicle development in mice.

Directory of Open Access Journals (Sweden)

Cheng Zhang

Full Text Available The mechanical method to isolate preantral follicle has been reported for many years. However, the culture systems in vitro are still unstable. The aim of this study was to analyze the effect of the culture system of mice preantral follicles on the follicular development in vitro. The results showed that the 96-well plate system was the most effective method for mice follicle development in vitro (volume change: 51.71%; survival rate: 89%, at day 4. Follicle-stimulating hormone (FSH and Thyroid hormone (TH are important for normal follicular development and dysregulation of hormones are related with impaired follicular development. To determine the effect of hormone on preantral follicular development, we cultured follicle with hormones in the 96-well plate culture system and found that FSH significantly increased preantral follicular growth on day 4. The FSH-induced growth action was markedly enhanced by T₃ although T₃ was ineffective alone. We also demonstrated by QRT-PCR that T₃ significantly enhanced FSH-induced up-regulation of Xiap mRNA level. Meanwhile, Bad, cell death inducer, was markedly down-regulated by the combination of hormones. Moreover, QRT-PCR results were also consistent with protein regulation which detected by Western Blotting analysis. Taken together, the findings of the present study demonstrate that 96-well plate system is an effective method for preantral follicle development in vitro. Moreover, these results provide insights on the role of thyroid hormone in increasing FSH-induced preantral follicular development, which mediated by up-regulating Xiap and down-regulating Bad.

Effects of follicle stimulationg hormone on {gamma}-ray irradiated immature mouse ovarian follicles

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Kyu; Lee, Chang Joo; Lee, Young Keun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Song, Kang Won; Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

1998-06-01

To assess the radioprotective effects of Follicle Stimulating Hormone (FSH) on ovarian follicles, 3 week-old female mice were irradiated with 8.33 Gy of {gamma}-ray (group R) and followed by 5 IU ip-injection of FSH (group RF). For control groups, 5 IU of saline (group C) or 5 IU of FSH (group F) was ip-injected. Ovaries were collected 0h, 6h, 12h, 1d, 2d, 4d, and 8d after irradiation or saline/FSH injection, and followed by fixation in neutral buffered formalin for routine histochemistry. Immunohistochemistry was used to assess the status of follicles and DNA fragmentation was analyzed by agarose gel electrophoresis for total DNA. Staining specific for apoptotic follicles showed high intensity at 6h and 12h in group R and RF. On the other hand, staining specific for proliferating follicles showed noticeably high intensity at 8d in group R and RF. DNA fragmentation of 185bp increased with time in all experimental groups. Especially 370bp appeared at 6h in group R, then disappeared after 1d. In case of group RF, it appeared at 12h and disappeared after 1d. From the above results, the irradiated antral follicles become completely disappeared from 4d to 8d, and then new follicles started to grow again at 8d. FSH had delaying or suppressing effects on follicular atresia after irradiation. In addition, it became clear that radiation-induced follicular atresia was mediated by granulosa cell apoptosis.

In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

Science.gov (United States)

Munier, Mathilde; Grouleff, Julie; Gourdin, Louis; Fauchard, Mathilde; Chantreau, Vanessa; Henrion, Daniel; Coutant, Régis; Schiøtt, Birgit; Chabbert, Marie; Rodien, Patrice

2016-01-01

Background: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p′-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p′-DDT exposure and reproductive abnormalities. Objectives: To investigate the putative effects of p,p′-DDT on the human follitropin receptor (FSHR) function. Methods and Results: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p′-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p′-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p′-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p′-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p′-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p′-DDT was dependent on the FSHR. In addition, p,p′-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p′-DDT and potentiation of the FSHR response to FSH by p,p′-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p′-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p′-DDT and 16a into the FSHR transmembrane bundle. Conclusion: p,p′-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein–coupled receptors are additional targets of endocrine disruptors. Citation: Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016

[Effect of polycystic ovary syndrome treated with the periodic therapy of acupuncture].

Science.gov (United States)

Yang, Danhong; Zhao, Mei; Tan, Jiahong

2017-08-12

To observe the effects differences for polycystic ovary syndrome (PCOS) between periodic therapy of acupuncture and diane-35 and to explore its mechanism. Sixty patients were randomly assigned into an acupuncture group and a western medication group, 30 cases in each one, 29 patients finally included with one case dropping out respectively. In the acupuncture group, periodic therapy was mainly used at bilateral Sanyinjiao (SP 6), Dahe (KI 12), Guilai (ST 29), Guanyuan (CV 4), Zhongji (CV 3), with different acupoints in the postmenstrual, intermenstrual, premenstrual periods, once every other day, 3 times a week. EA (2 Hz/100 Hz) was used at bilateral Dahe (KI 12) and Guilai (ST 29). If treatment, FSH increased and LH, LH/FSH, T decreased in the two groups (all P medication group were better than those in the acupuncture group (both P medication group, diane-35 was prescribed orally for 21 days as a course, with 7 days at interval, one tablet a day. All the treatment was started on the fifth day of the menstrual circle, for continuously 3 months. The indexes were observed before and after treatment, including the menstrual circle, acne score, body mass index (BMI), serum follicle stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH and testosterone (T). The effects of the two groups were compared. The total effective rate was 75.9% (22/29) in the acupuncture group, which was not significantly different from 79.3% (23/29) in the western medication group ( P >0.05). The menstrual cycles were shorter after treatment in the two groups (both P 0.05). After treatment,FSH increased and LH,LH/FSH,T decreased in the two groups (all P medication group were better than those in the acupuncture group (both P <0.05). Conclusion Periodic therapy of acupuncture is probably one of the effective methods for PCOS,which can improve patients' clinical symptoms,sex hormone level,and menstrual cycle.

A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

Science.gov (United States)

Elhadd, Tarik A; Ghosh, Sujoy; Teoh, Wei Leng; Trevethick, Katy Ann; Hanzely, Zoltan; Dunn, Laurence T; Malik, Iqbal A; Collier, Andrew

2009-08-01

Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.

"hCG priming" effect in controlled ovarian stimulation through a long protocol

Directory of Open Access Journals (Sweden)

Antsaklis Aris

2009-08-01

Full Text Available Abstract Background Recently, it has been demonstrated that, in patients down-regulated by GnRH analogues (GnRHa, a short-term pre-treatment with recombinant LH (rLH, prior to recombinant FSH (rFSH administration, increases the number of small antral follicle prior to FSH stimulation and the yield of normally fertilized embryos. However, no data exist in the literature regarding the potential beneficial effect of "hCG priming" in controlled ovarian hyperstimulation (COH through a long GnRH-a protocol, which binds the same receptor (LH/hCGR, though it is a much more potent compared to LH. The primary aims of this study were to assess the effect of short-term pre-rFSH administration of hCG in women entering an ICSI treatment cycle on follicular development, quality of oocytes and early embryo development. The secondary endpoints were to record the effects on endometrial quality and pregnancy rate. Methods Patients with a history of at least one previous unsuccessful ICSI cycle were randomly assigned into two groups to receive treatment with either a long protocol with rFSH (control group or a long protocol with rFSH and pre-treatment with hCG (hCG group. In particular, in the latter group, a fixed 7 days course of 200 IU/day hCG was administered as soon as pituitary desensitization was confirmed. Results The mean number of oocytes retrieved was not significantly different between the two treatment groups, although the percentage of mature oocytes tended to be higher but not significantly different in hCG-treated patients. The percentage of patients with more than one grade 3 embryos was higher in the pre-treatment group, which also showed a higher pregnancy rate. Conclusion All the above clinical observations, in conjunction with previous data, suggest a point towards a beneficial "hCG priming" effect in controlled ovarian hyperstimulation through a long GnRH-a down-regulation protocol, particularly in patients with previous ART failures.

Ovarian response markers lead to appropriate and effective use of corifollitropin alpha in assisted reproduction.

Science.gov (United States)

La Marca, Antonio; D'Ippolito, Giovanni

2014-02-01

Corifollitropin alpha is a highly effective gonadotrophin, which maintains multifollicular growth for a week. The advantages of its administration include ease of use of the drug, making the treatment more patient friendly, resulting in a lower level of distress for the patient. At the same time, the pregnancy rate resulting from its use in IVF/intracytoplasmic sperm injection cycles is similar to that found when daily recombinant FSH is administered. The ovarian response to corifollitropin alpha is dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There is a general trend towards a higher ovarian response with an increasing AFC and the number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome following corifollitropin alpha is very similar to the rate reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve at risk of overstimulation, and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Corifollitropin alpha is a highly effective gonadotrophin which maintains multifollicular growth for a week. The ovarian response to corifollitropin was demonstrated to be dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There was a general trend toward a higher ovarian response with an increasing AFC and the mean number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome (OHSS) following corifollitropin alpha is very similar to the rate of OHSS reported in literature for young women undergoing IVF, the risk of overstimulation may be

Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bahnsen, M; Bennett, Patrick

1983-01-01

). No significant difference was observed when comparing serum testosterone concentrations. Patients were divided into three groups in accordance with the severity of liver cirrhosis, using biochemical and clinical criteria. Patients with the best-preserved liver function (no. = 11) and patients with moderately...... affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed...... groups of patients. Dexamethasone suppression did not change the concentration of testosterone significantly, but oestrone and oestradiol concentrations decreased significantly (P less than 0.01) in controls and patients. In patients, but not in controls, a significant (P less than 0.01) increase in FSH...

Observational Study to Assess the Therapeutic Value of Four Ovarian Hyperstimulation Protocols in IVF After Pituitary Suppression with GnRH Antagonists in Normally Responding Women.

Science.gov (United States)

Ana, Monzó; Vicente, Montañana; María, Rubio José; Trinidad, García-Gimeno; Alberto, Romeu

2011-02-22

To compare the clinical results of four different protocols of COH for IVF-ICSI in normovulatory women, using in all cases pituitary suppression with GnRH antagonists. A single center, open label, parallel-controlled, prospective, post-authorization study under the approved conditions for use where 305 normal responders women who were candidates to COH were assigned to r-FSH +hp-hMG (n = 51, Group I), hp-hMG (n = 61, Group II), fixed-dose r-FSH (n = 118, Group III), and r-FSH with potential dose adjustment (n = 75, Group IV) to subsequently undergo IVF-ICSI. During stimulation, Group IV needed significantly more days of stimulation as compared to Group II [8.09 ± 1.25 vs. 7.62 ± 1.17; P women undergoing pituitary suppression with GnRH antagonists.

Serum level modifications of female sex hormones after radiocastration with different total doses

International Nuclear Information System (INIS)

Naujokat, B.; Rohloff, R.; Willich, N.; Eiermann, W.

1988-01-01

We determined serum level of estradiol, FSH and LH over a period of six to eight weeks after ovarian irradiation for castration with different doses (2x2.5 Gy/3x2.5 Gy/4x2.5 Gy) in 15 patients with metastatic breast cancer as compared to changes after ovarectomy in five patients. The time course of the changing estradiol-, FSH and LH-serum levels sigificantly depends on the ovarian dose. After radiological castration with a dose of 4x2.5 Gy = 10 Gy in four days the estrogen levels decrease within two to three weeks, and the FSH- and LH-levels increase after three to four weeks into the postmenopausal range. Therefore, the time course is not very different from changes after ovarectomy. (orig.) [de

Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

Science.gov (United States)

Dalterio, S; Steger, R; Mayfield, D; Bartke, A

1984-01-01

Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

Development of radioimmunoassay techniques for measurement of gonadotrophins and other hormones with application in pharmacological studies of the anterior hypophysis in man. Part of a coordinated programme on in vitro assay techniques

International Nuclear Information System (INIS)

Simionescu, L.

1975-01-01

Human studies were performed on psychiatric patients, patients under thyroidectolmy stress and normal individuals. Radioimmunoassay determined HGH, insulin, LH, FSH and testosterone in basal condition in psychiatric patients and in normal subjects. The same hormones were also measured in untreated psychiatric patients during and acute administration of chlorpromazine (CPZ). Changes in insulin, LH, FSH and testosterone remained within the limits of variation generally observed in or between individuals. The HGH level was increased paradoxically after CPZ administration in some parapsychiatric untreated patients. Constant increase in prolactin was observed both in chronic treated patients and during acute administration of CPZ. Measuring HGH, insulin, LH, FSH or testosterone during acute administration of CPZ does not appear to be relevant model for studying the influence of this drug on hormone release. The release of GH during thyroidectomy for hyperthyroidia proved similar to release during general surgery, while release of prolactin is lower. The reasons for this are discussed. Radioimmunoassay gave data on GH in infants, children and adolescents. Measurement of GH levels during an acute test (insulin and glucagon) allowed classification of hypostatural children into ''pituitary dwarfism'', ''non-pituitary dwarfism'' and ''limited response dwarfism''. A doubling of LH levels appeared at the 13-14 year age interval for both sexes. The hypophyseal and serum TSH was investigated in male adult rats exposed to cold, under immobilization stress or receiving substances acting as chemical suppressors (methyliouracyls) or neurotropic substances (benzoactamine and amphetamine). The variations were classified in the percentual and multiplicative area in animals receiving neurotropic substances or exposed to metabolic sollicitations, while order of magnitude area of variation was observed after chemical suppression of thyroid function. The TSH determined by radioimmunoassay

A Proteomic Analysis of Human Follicular Fluid: Comparison between Younger and Older Women with Normal FSH Levels

Directory of Open Access Journals (Sweden)

Mahmoud Hashemitabar

2014-09-01

Full Text Available The follicular fluid (FF is produced during folliculogenesis and contains a variety of proteins that play important roles in follicle development and oocyte maturation. Age-related infertility is usually considered as a problem that can be solved by assisted reproduction technology. Therefore, the identification of novel biomarkers that are linked to reproductive aging is the subject of this study. FF was obtained from healthy younger (20–32 years old and older (38–42 years old women undergoing intracytoplasmic sperm injection (ICSI due to male factor infertility. The FF was analyzed by two-dimensional gel electrophoresis (2-DE. The power of two-dimensional gel electrophoresis and the identification of proteins were exploited using matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI-TOF-TOF mass spectrometry. Twenty three protein spots showed reproducible and significant changes in the aged compared to the young group. Of these, 19 protein spots could be identified using MALDI-TOF-TOF-MS. As a result of MASCOT search, five unique downregulated proteins were identified in the older group. These were identified as serotransferrin, hemopexin precursor, complement C3, C4 and kininogen. A number of protein markers were found that may help develop diagnostic methods of infertility.

Inhibin secretion in women with the polycystic ovary syndrome before and after treatment with progesterone

Directory of Open Access Journals (Sweden)

Anifandis George

2011-04-01

Full Text Available Abstract Objectives It has been suggested that inhibin secretion is altered in women with the polycystic ovary syndrome (PCOS. However, the contribution of a preceding luteal phase has not been taken into account. The aim of the present study was to investigate whether progesterone in the context of a simulated luteal phase affects basal and FSH-induced inhibin secretion in women with PCOS and elevated LH. Methods Ten women with PCOS and 8 normally cycling women participated in an experimental procedure (Exp involving the administration of a single injection of recombinant FSH (450 IU sc. In the women with PCOS, the procedure was performed before (Exp 1 and after a 20-day treatment with progesterone (Exp 2, while in the normal women on day 2 of the cycle (Exp 3. Inhibin A and B levels were measured in blood samples taken before and 24 hours after the FSH injection. Results Basal LH levels were significantly higher and inhibin A levels were significantly lower in the PCOS group compared to the control group, while inhibin B levels were comparable in the two groups. In the PCOS group, after treatment with progesterone inhibin A and LH but not inhibin B levels decreased significantly (p Conclusions In women with PCOS, as compared to control women, the dissimilar pattern of inhibin A and inhibin B secretion in response to FSH appears to be independent of a preceding simulated luteal phase. It is possible that compared to normal ovaries, the PCOS ovaries are less sensitive to endogenous LH regarding inhibin A secretion and more sensitive to exogenous FSH stimulation in terms of inhibin A and inhibin B secretion.

Comparison of the effects of laparoscopic bipolar electrocoagulation and intracorporeal suture application to ovarian reserve in benign ovarian cysts.

Science.gov (United States)

Özgönen, Hakan; Erdemoglu, Evrim; Günyeli, Ilker; Güney, Mehmet; Mungan, Tamer

2013-04-01

Aim of the present study is to determine the effects of bipolar electrocoagulation and intracorporeal suture on the ovarian reserve after ovarian cystectomy. Sixty patients aged 18-42 years old and with a persistent adnexal mass were recruited to the study. Patients were randomized into suture hemostasis group or bipolar hemostasis group. Laparoscopic ovarian cystectomy was performed to all patients. Hemostasis was obtained by bipolar coagulation in 30 patients and by intracorporeal sutures in 30 patients. Serum levels of FSH, LH, estradiol, inhibin B and ultrasonographic measurements (antral follicle count and ovarian volume) were analyzed and recorded at day 3 of menstrual cycle, 1 and 3 months after the surgery. Basal FSH level measurement at the postoperative third month was significantly increased to 6.96 ± 1.86 mIU/ml (p electrocoagulation group. However, the decreased ovarian volume and antral follicle count was restored at the postoperative third month in the bipolar electrocoagulation group. Preoperative and postoperative FSH, LH, estradiol and inhibin B levels and ultrasonographic measurements were similar in the intracorporeal suture group. The unwanted effect of bipolar electrocoagulation on ovarian reserve is probably transient and causes minimal damage to ovary. FSH levels may be slightly elevated. Gentle use of bipolar electrocoagulation or intracorporeal are not found to effect ovarian reserve.

Amenorrhea secondary to a vismodegib-induced blockade of follicle-stimulating hormone-receptor activation.

Science.gov (United States)

Strasswimmer, John; Latimer, Benjamin; Ory, Steven

2014-08-01

To report a novel mechanism suggestive of early ovarian failure secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib. Case report and literature review. Academic and private dermatology and fertility practices. A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib. Physical examination and endocrine evaluation. Elevated follicle-stimulating hormone (FSH) and low estrogen in the setting of a normal anti-Müllerian hormone. FSH was elevated; estrogen was low. Preantral follicles were detected and anti-Müllerian hormone activity was normal. Menses resumed 5 weeks after cessation of therapy. Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway is indicated for advanced basal cell carcinoma and is associated with amenorrhea. The mechanism is unknown; it has some features of ovarian failure but preserves ovarian potential through blockading of FSH-receptor-dependent signal transduction. This effect appears to be rapidly reversible upon cessation of therapy. Vismodegib and related compounds may have potential for a role in intervention for gynecologic and endocrine disorders and in therapy for other issues involving FSH-dependent function. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Predictors of in vitro fertilization outcomes in women with highest follicle-stimulating hormone levels ≥ 12 IU/L: a prospective cohort study.

Directory of Open Access Journals (Sweden)

Lina N Huang

Full Text Available The purpose of this study is to evaluate factors predictive of outcomes in women with highest follicle-stimulating hormone (FSH levels ≥ 12 IU/L on basal testing, undergoing in vitro fertilization (IVF.A prospective cohort study was conducted at Stanford University Hospital in the Reproductive Endocrinology and Infertility Center for 12 months. Women age 21 to 43 undergoing IVF with highest FSH levels on baseline testing were included. Donor/Recipient and frozen embryo cycles were excluded from this study. Prognostic factors evaluated in association with clinical pregnancy rates were type of infertility diagnosis and IVF stimulation parameters.The current study found that factors associated with clinical pregnancy were: increased number of mature follicles on the day of triggering, number of oocytes retrieved, number of Metaphase II oocytes if intracytoplasmic sperm injection was done, and number of embryos developed 24 hours after retrieval.Our findings suggest that it would be beneficial for women with increased FSH levels to attempt a cycle of IVF. Results of ovarian stimulation, especially embryo quantity appear to be the best predictors of IVF outcomes and those can only be obtained from a cycle of IVF. Therefore, increased basal FSH levels should not discourage women from attempting a cycle of IVF.

Electroacupuncture Modulates Reproductive Hormone Levels in Patients with Primary Ovarian Insufficiency: Results from a Prospective Observational Study

Directory of Open Access Journals (Sweden)

Kehua Zhou

2013-01-01

Full Text Available To investigate the effects of electroacupuncture (EA on serum FSH, E2, and LH levels, women with primary ovarian insufficiency (POI were treated with EA once a day, five times a week for the first four weeks and once every other day, three times a week, for the following two months, and then were followed up for three months. Serum E2, FSH, and LH levels were measured at baseline, at the end of treatment, and during followup. A total of 11 women with POI were included in this prospective consecutive case series study. Compared with baseline, patients’ serum E2 increased, FSH decreased, and LH decreased (P=0.002, 0.001, and 0.002, resp. after EA treatment, and these effects persisted during followup. With treatment, 10 patients resumed menstruation (10/11, 90.91%, whereas one patient remained amenorrhea. During followup, two patients, including the one with amenorrhea during treatment, reported absence of menstruation. Temporary pain occurred occasionally, and no other adverse events were found during treatment. The results suggest that EA could decrease serum FSH and LH levels and increase serum E2 level in women with POI with little or no side effects; however, further randomized control trials are needed.

Early effects of cranial irradiation on hypothalamic-pituitary function

International Nuclear Information System (INIS)

Lam, K.S.; Tse, V.K.; Wang, C.; Yeung, R.T.; Ma, J.T.; Ho, J.H.

1987-01-01

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT

Influence of apricot kernels on blood plasma levels of selected anterior pituitary hormones in male and female rabbits in vivo

Directory of Open Access Journals (Sweden)

Katarína Michalcová

2016-05-01

Full Text Available Amygdalin is represented in the family Rosacea more precisely in an apricot kernels and an almonds. There are a lot of components such as trace elements, vitamins, carbohydrates, organic acids, esters, phenols, terpenoids, except cyanogenic glycoside in the seeds. It is known that bioregulators can modulate the activity of specific enzymes and hormones very exactly at low levels and in a short time. The aim of our study was examine the effects of selected doses (0, 60, 300, 420 mg/kg b.w. of apricot kernels in feed on the plasma levels of anterior pituitary hormones in young male and female rabbits in vivo. A sensitive, biochemical method, ELISA was used to determine the hormones prolactin (PRL, luteinizing hormone (LH and follicle stimulating hormone (FSH. 28-day application of apricot kernels did not affect the concentration of PRL, LH, FSH in blood plasma of males. No significant (P≤0.05 differences in case of PRL and LH levels in the blood plasma of females were found. On the other hand a significant (P≤0.05 inhibition of FSH release induced by kernels at the doses 300, 420 mg/kg was found. Our results indicate that apricot kernels could affect secretion of anterior pituitary hormone FSH in female rabbits.

Serum inhibin B in healthy pubertal and adolescent boys

DEFF Research Database (Denmark)

Andersson, A M; Juul, A; Petersen, J H

1997-01-01

correlated strongly with age, and when the effect of age was taken into account, only the partial correlation between inhibin B and LH/testosterone remained statistically significant. At stage II of puberty, the positive partial correlation between inhibin B and LH/testosterone was still present. At stage......Inhibin B levels were measured in serum from 400 healthy Danish prepubertal, pubertal, and adolescent males, aged 6-20 yr, in a cross-sectional study using a recently developed immunoassay that is specific for inhibin B, the physiologically important inhibin form in men. In addition, serum levels...... of FSH, LH, testosterone, and estradiol levels were measured. Serum levels of inhibin B, FSH, LH, testosterone, and estradiol all increased significantly between stages I and II of puberty. From stage II of puberty the inhibin B level was relatively constant, whereas the FSH level continued to increase...

Standardised multicentre procedure for plasma gonadotrophin radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Ferguson, K M; Hayes, M; Jeffcoate, S L [Chelsea Hospital for Women, London (UK)

1982-09-01

A radioimmunoassay method for the assay of luteinising hormone (LH) and follicle-stimulating hormone (FSH) in serum/plasma has been designed for use in laboratories of varying expertise in the United Kingdom. The major sources of experimental error leading to poor within-laboratory performance and between-laboratory comparability were identified: quality of tracer, use of calibration standards, and separation procedure. A simple rugged kit was designed which was extensively tested first in our laboratory and then in a small multi-centre field trial before being made available. It is now used routinely by 26 health service and research laboratories. The working range of the assays is 1-50 IU/l (LH) and 0.3-16 IU/l (FSH). The between-batch reproducibility was 5-11% (CV) over the dose range 4.8-18 IU/l (LH) and 1.6-15 IU/l (FSH).

Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target.

Science.gov (United States)

Perales-Puchalt, Alfredo; Svoronos, Nikolaos; Rutkowski, Melanie R; Allegrezza, Michael J; Tesone, Amelia J; Payne, Kyle K; Wickramasinghe, Jayamanna; Nguyen, Jenny M; O'Brien, Shane W; Gumireddy, Kiranmai; Huang, Qihong; Cadungog, Mark G; Connolly, Denise C; Tchou, Julia; Curiel, Tyler J; Conejo-Garcia, Jose R

2017-01-15

To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells. FSHR expression was determined by Western blotting, immunohistochemistry, and qPCR in 77 human ovarian cancer specimens from 6 different histologic subtypes and 20 human healthy tissues. The effectiveness of human T cells targeted with full-length FSH in vivo was determined against a panel of patient-derived xenografts. Safety and effectiveness were confirmed in immunocompetent tumor-bearing mice, using constructs targeting murine FSHR and syngeneic T cells. FSHR is expressed in gynecologic malignancies of different histologic types but not in nonovarian healthy tissues. Accordingly, T cells expressing full-length FSHR-redirected chimeric receptors mediate significant therapeutic effects (including tumor rejection) against a panel of patient-derived tumors in vivo In immunocompetent mice growing syngeneic, orthotopic, and aggressive ovarian tumors, fully murine FSHR-targeted T cells also increased survival without any measurable toxicity. Notably, chimeric receptors enhanced the ability of endogenous tumor-reactive T cells to abrogate malignant progression upon adoptive transfer into naïve recipients subsequently challenged with the same tumor. Interestingly, FSHR-targeted T cells persisted as memory lymphocytes without noticeable PD-1-dependent exhaustion during end-stage disease, in the absence of tumor cell immunoediting. However, exosomes in advanced tumor ascites diverted the effector activity of this and other chimeric receptor-transduced T cells away from targeted tumor cells. T cells redirected against FSHR + tumor cells with full-length FSH represent a promising therapeutic alternative against a broad range of ovarian malignancies, with negligible toxicity even in the presence of cognate targets in tumor-free ovaries. Clin Cancer Res; 23(2); 441-53. ©2016 AACR. ©2016 American Association for Cancer Research.

Composition of cross-linked 125I-follitropin-receptor complexes

Energy Technology Data Exchange (ETDEWEB)

Shin, J.; Ji, T.H.

1985-10-15

Both of the alpha and beta subunits of intact human follitropin (FSH) were radioiodinated with SVI-sodium iodide and chloramine-T and could be resolved on sodium dodecyl sulfate-polyacrylamide gels. Radioiodinated FSH was affinity-cross-linked with a cleavable (nondisulfide) homobifunctional reagent to its membrane receptor on the porcine granulosa cell surface as well as to a Triton X-100-solubilized form of the receptor. Cross-linked samples revealed three additional bands of slower electrophoretic mobility, corresponding to 65, 83, and 117 kDa, in addition to the hormone bands. The hormone alpha beta dimer band corresponded to 43 kDa. Formation of the three bands requires the SVI-hormone to bind specifically to the receptor with subsequent cross-linking. Binding was prevented by an excess of the native hormone but not by other hormones. A monofunctional analog of the cross-linking reagent failed to produce the three bands. Reagent concentration-dependent cross-linking revealed that their formation was sequential; smaller complexes formed first and then larger ones. When gels of cross-linked complexes were treated to cleave covalent cross-links and then electrophoresed in a second dimension, 18-, 22-, and 34-kDa components were released, in addition to the alpha and beta subunits of the hormone.

Nickel nanoparticles exposure and reproductive toxicity in healthy adult rats.

Science.gov (United States)

Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

2014-11-17