scholarly journals Gonadotropin Glycoforms Circulating in Women Using Progestins of the Levonorgestrel Family for Contraception

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Karin Eriksson ◽  
Leif Wide

Abstract Context The progestins of the levonorgestrel family are 13-ethylgonane progestins, commonly used for contraception in women. One contraceptive effect of these progestins is inhibition of ovulation, which may be a result of changes in gonadotropin glycosylation patterns. Gonadotropin glycoforms differ in number of glycans and bioactivity: more bioactive low-N-glycosylated glycoforms, diglycosylated luteinizing hormone (LHdi) and triglycosylated follicle-stimulating hormone (FSHtri), and less bioactive fully N-glycosylated glycoforms, LHtri and FSHtetra. Objective Characterize the glycosylation patterns on the circulating gonadotropin glycoforms in women using 13-ethylgonane progestins for contraception. Design, Subjects, Main Outcome Measures Serum samples, collected from 92 healthy women using 13-ethylgonane progestins for contraception, were included. Forty women used progestin-only continuously and 52 used progestins combined with ethinylestradiol (EE) for 3 weeks followed by a hormone-free week. Concentration, sulfonation, and sialylation of each glycoform were determined and compared with follicular phase values of normal menstrual cycles. Results The progestin-only group had significantly increased serum levels, decreased sulfonation, and increased sialylation of LHdi. The LHdi/FSHtri ratio was increased. The progestin+EE group had significantly decreased gonadotropin glycoform concentrations and decreased sialylation of FSHtri. The progestin+EE effect on sialylation of FSHtri occurred later during the treatment cycle in contrast to the effect on FSHtri concentration. Conclusions The 2 different progestin treatments induced different effects on the glycan synthesis and concentrations of more bioactive low-glycosylated gonadotropins. Progestin-only treatment increased sialylation and decreased sulfonation of LHdi molecules, contributing to sustained higher levels of bioactive LHdi molecules. Progestin+EE treatment decreased sialylation of FSHtri, contributing to a shorter half-life and decreased levels of bioactive FSHtri.

1968 ◽  
Vol 59 (2) ◽  
pp. 298-306 ◽  
Author(s):  
Melvin L. Taymor ◽  
Toshihiro Aono ◽  
Carolyn Pheteplace

ABSTRACT The serum levels of FSH and LH were determined in 11 normal menstrual cycles by radioimmunoassay. The results of LH assay demonstrated a consistent pattern with a sharp 3 to 4 fold increase occurring on the average 13.9 days before the next menses. The changes in FSH levels during the cycle were neither as marked nor as consistent. Three distinct patterns seemed to emerge. However, the mean levels of FSH from the 11 cycles demonstrated a significant high level 12 days before, a low level 1 day before and another rise 1 day after the midcycle peak of LH.


1989 ◽  
Vol 121 (1) ◽  
pp. R9-R12 ◽  
Author(s):  
H. M. Fraser ◽  
D. M. Robertson ◽  
D. M. De Kretser

ABSTRACT Concentrations of immunoreactive inhibin in serum samples collected daily from six adult stumptailed female macaques during normal menstrual cycles were measured with a heterologous radioimmunoassay. Serum inhibin concentrations were low during the follicular phase of the cycle. After ovulation they began to rise, reaching a plateau between 8 and 11 days, before falling in parallel with the decline in luteal progesterone secretion. The dependence of the inhibin secretion by the corpus lutem on pituitary gonadotrophins was investigated by the administration of an LHRH antagonist [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10]LHRH once daily for 3 days beginning on day 8 of the luteal phase in six macaques. LHRH antagonist treatment markedly suppressed serum levels of inhibin and progesterone and these remained at the level found in the follicular phase for the remainder of the luteal phase. These results show that inhibin in the macaque is secreted into the peripheral blood almost exclusively during the luteal phase, being highest when FSH is at its nadir. Suppression of serum inhibin concentrations during the luteal phase by LHRH antagonist suggests that its secretion is integrated with the LH control of the corpus luteum.


1990 ◽  
Vol 122 (1) ◽  
pp. 96-100 ◽  
Author(s):  
Ulrich Fingscheidt ◽  
Gerhard F. Weinbauer ◽  
Shafiq A. Khan ◽  
Eberhard Nieschlag

Abstract. Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH.


1974 ◽  
Vol 75 (3) ◽  
pp. 491-496 ◽  
Author(s):  
Junichi Mori ◽  
Hiroshi Nagasawa ◽  
Reiko Yanai ◽  
Junji Masaki

ABSTRACT The sequence of changes in the serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from 2 days before to 24 h after parturition of primiparous Sprague-Dawley rats was investigated by radioimmunoassay. No appreciable change in average serum FSH levels was observed during 2 days before and 1 h after parturition. After this the levels increased gradually to show a peak at 7 h after parturition and then declined gradually until 24 h after parturition. However, the level at 24 h after parturition was still twice as high as that at parturition (0 h). The average serum LH levels which were low between 2 days before and 1 h after parturition, showed a peak at 7 h and decreased toward 13 h after parturition. The same levels as at parturition were maintained between 13 and 24 h after parturition. The time of surge of either FSH or LH was closely related to the time after parturition. There were some differences between FSH and LH in the patterns of sequence of changes in the serum levels near parturition.


2018 ◽  
Vol 23 ◽  
pp. 2515690X1879605 ◽  
Author(s):  
Nourollah Rezaei ◽  
Tahereh Mardanshahi ◽  
Majid Malekzadeh Shafaroudi ◽  
Saeed Abedian ◽  
Hamid Mohammadi ◽  
...  

The present study was designed to investigate the antioxidant property of l-carnitine (LC) on serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TH) and testis oxidative stress in streptozotocin (STZ)-induced diabetic rats. The rats were divided into the following groups: group I, control; group II, LC 100 mg/kg/d; group III, diabetic; and groups IV to VI, diabetic rats treated with 50, 100, and 200 mg/kg/d of LC, respectively. Daily injections were given intraperitoneally for 7 weeks. At the end of experimental period, after sacrificing the rats, FSH, LH, TH, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), mitochondrial function (MTT), protein carbonyl (PC), and reactive oxygen species (ROS) levels were measured. STZ caused an elevation of MDA, ROS, and PC ( P < .001) with reduction of GSH, CAT, TAC, and MTT ( P < .001) in the serum levels. Group VI had significantly increased FSH, LH, and TH levels versus the untreated diabetic group ( P < .001). Although groups V and VI significantly decreased MDA ( P < .001), PC ( P < .01), and ROS ( P < .01) compared with the untreated diabetic group; only in group VI, the activity of GSH ( P < .001), CAT ( P < .01), TAC ( P < .001), and MTT ( P < .001) significantly increased. The results of the present study suggest that LC decreased diabetes-induced oxidative stress complications and also improved serum level of FSH, LH, and TH by reducing levels of lipid peroxidation and increasing antioxidant enzymes.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2748-2748 ◽  
Author(s):  
Marcel Reiser ◽  
Michael K. Wenger ◽  
Christina Nickenig ◽  
N. Peter ◽  
Christian Kuhn ◽  
...  

Abstract Background: The combination of Rituximab and CHOP is considered the standard of treatment for DLBCL in elderly patients (pts) but there is hardly any data on the pharmacokinetic of Rituximab in aggressive lymphoma pts. Objective: To study serum levels and pharmacokinetic properties of Rituximab when combined with dose dense CHOP-14 in elderly DLBCL patients Methods: Blood samples of 18 pts were taken before and after Rituximab-infusion at each chemotherapy cycle. Additional samples were taken after the end of treatment and at the following timepoints: after 1 week, 1 month, 2 months, 3 months, 6 months and 9 months, respectively. Serum samples were taken within a maximum of 30 min, centrifuged at 1000 g for 10 min (room temperature) and stored at −20 degrees C. Batch samples were shipped to Xendo Lab., Groningen, The Netherlands, and analysed. The measured values were analysed by pharmakokinetic software MW/PHARM, version 3.50; (MediWare, 9800 AB Zuidhorn, The Netherlands) Additionally, a simulation of expected Rituximab-PK was performed taking into account 5 clinical trials, totalling 3777 observations in 264 patients mostly FL. Results: Median (range) age of pts was 69 (61–79) years. 10/18 pts had advanced stage (III/IV), 4/18 pts had bulky disease. Pts received a median (range) dose of 683 (545–791) mg Rituximab/cycle. Response to treatment was 15/18 CR/Cru, 2/18 PR,1/18 PD. The median (range) of trough serum Rituximab-levels (μg/ml) before each cycle were: #1 0(0–0); #2 39(18–61); #3 74(47–109); #4 95(40–136); #5 113(55–157); #6 114(12–518); #7 125(72–207);#8 117(75–304). After therapy Rituximab-levels were: 163(68–248) at 1 week; 101(44–163) at 1 month, 55(11–122) at 2 months, 33(6–577) at 3 months; 5(0–103) at 6 months, 0.7(0–128) at 9 months. 7 pts were evaluable at 9 months with 4/7 pts showed detectable Rituximab-levels. Thus, actual serum levels detected fit exactly the model calculated from data of patients with FL. A preliminary PK analysis of Rituximab according to a two-compartment model showed a long median (range) serum half-life (t 1/2) of 765 h (543–1092). Conclusion: In the dose dense bi-weekly regimen R-CHOP-14 Rituximab-serum levels increased slowly up to cyle 5. During cycle 5– 8 the serum Rituximab-levels reached a plateau and decreased constantly after the end of treatment with detectable levels even after 9 months and a long serum half-life. Increasing serum levels in the first four cycles are due to saturation kinetics of Rituximab. Based on this data the German High Grade NHL Study Group (DSHNHL) further investigates a dose escalation of Rituximab in the first cycles in order to improve treatment outcome.


1976 ◽  
Vol 83 (4) ◽  
pp. 684-691 ◽  
Author(s):  
Sven Johan Nillius ◽  
Leif Wide

ABSTRACT Modulating effects of oestradiol-17β and progesterone on the pituitary responsiveness to luteinizing hormone-releasing hormone (LRH) were investigated in 12 women with functional amenorrhoea. The pituitary reserve capacity for gonadotrophin section was investigated with repeated intravenous LRH tests before and after administration of oestradiol-1β followed by either progesterone or saline. Intramuscular injection of 1 mg of oestradiol-17β benzoate resulted in a suppression of both the basal gonadotrophin levels in serum and the gonadotrophin responses to LRH 24 h later. Progesterone, 25 mg im, was then administered in eleven experiments. Six h later, when the mean serum progesterone level had increased to levels similar to those seen in the early post-ovulatory phase of the menstrual cycle, there was a marked augmentation of the pituitary capacity to release both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in response to LRH. This was not found in eight experiments where saline was given instead of progesterone after oestrogen pretreatment. These findings suggest that the greatly increased pituitary sensitivity to LRH at midcycle may be caused not only by the oestradiol increase in blood during the late follicular phase but also in part by the small pre-ovulatory rise of progesterone during the mid-cyclic LH peak. Furthermore, they add further support to the hypothesis that progesterone as well as oestradiol is involved in the induction of the LH peak at midcycle. Progesterone may be of importance to secure the release of enough LH for ovulation and normal corpus luteum formation to occur.


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