scholarly journals Stimulation with recombinant FSH acutely and significantly increases inhibin B and estradiol in women after GnRH antagonist treatment: a model to study FSH regulation of ovarian function

2018 ◽  
Vol 110 (4) ◽  
pp. e251
Author(s):  
K. Kuhn ◽  
A. Bradford ◽  
A.J. Polotsky

Author(s):  
Maria Francesca Messina ◽  
Tommaso Aversa ◽  
Giuseppina Salzano ◽  
Daria Costanzo ◽  
Concetta Sferlazzas ◽  
...  

AbstractPrimary gonadal failure may occur in most individuals with Turner syndrome (TS). Since ovaries in TS girls undergo premature apoptosis and cryopreservation of ovarian tissue is now feasible, it would be useful to identify a reliable marker of ovarian reserve in these patients. We planned to evaluate ovarian function in a group of TS patients by measuring both traditional markers and inhibin B and to compare these results with those of a control group.We enrolled 23 patients with TS and 17 age-matched healthy girls. The median age of our TS patients was 17.6 years. Three out of the 23 patients (13%) showed spontaneous pubertal development and regular menstrual cycles; the remaining 20 (86.9%) presented with primary amenorrhea.The median level of inhibin B in the TS patients with primary amenorrhea was 42 pg/mL and did not differ significantly among the different subgroups in relation to karyotype. The median inhibin B level in the control group was significantly higher than in the TS girls with primary amenorrhea (83 vs. 42 pg/mL, p<0.00001). In the three patients with TS and spontaneous menstrual cycles, the inhibin B levels were significantly higher when compared to the values of the TS girls with primary amenorrhea.TS patients with primary amenorrhea have significantly lower levels of inhibin B than TS girls with spontaneous puberty and healthy controls. Inhibin B does not correlate with follicle-stimulating hormone/luteinizing hormone. If our results are confirmed in further studies, inhibin B could become a first-line screening test for assessing ovarian reserve and a longitudinal marker of the possible decline of ovarian function in TS.





2004 ◽  
Vol 183 (3) ◽  
pp. 595-604 ◽  
Author(s):  
A V Sirotkin ◽  
P Sanislo ◽  
H-J Schaeffer ◽  
I Florkovičová ◽  
J Kotwica ◽  
...  

Thrombopoietin (TPO) is known to be involved in megakariocytopoesis, but its role in the control of ovarian function is unknown. The aims of this study were to determine whether TPO can regulate the proliferation, apoptosis and secretory activity of ovarian cells, to identify possible intracellular mediators of TPO action, especially protein kinase A (PKA), and to define their interrelationships within ovarian cells. We investigated the effect of TPO treatment (0, 1, 10 or 100 ng/ml) on the following characteristics of cultured porcine ovarian follicles, determined using SDS-PAGE and Western blotting, immunocytochemistry, RIA and ELISA: the expression of intracellular peptides associated with proliferation (PCNA), apoptosis (Bax), tyrosine kinase (TK, phosphotyrosine), Cdc2/p34 kinase, PKA and the transcription factor CREB-1, and the secretion of progesterone, androstenedione, estradiol-17β, oxytocin, inhibin A, inhibin B, IGF-I, transforming growth factor-2β (TGF-2β) and IGF-binding protein 3 (IGFBP-3). The involvement of PKA-dependent pathways was examined by evaluating the effect of a PKA blocker (KT5720, 1 μg/ml), either alone or in combination with TPO, on the parameters listed above. A TPO-induced increase in expression of PCNA, Bax, PKA, TK, Cdc2/p34 and CREB was observed. Furthermore, TPO was able to inhibit androstenedione, estradiol, TGF-2β and IGFBP-3 secretion, and to stimulate oxytocin, inhibin A, inhibin B and IGF-I secretion. Progesterone secretion was not stimulated. The PKA blocker KT5720, when given alone, reduced the expression of Bax and TGF-2β, augmented the expression of PKA, CREB and oxytocin, but did not influence the secretion of progesterone, androstenedione, estradiol, IGFBP-3, inhibins A and B or IGF-I. When given together with TPO, the PKA blocker prevented or reversed the action of TPO on PKA, CREB, androstenedione, estradiol, IGFBP-3, oxytocin, but not its effect on Bax, TGF-2β or inhibin B. On the other hand, treatment with KT5720 augmented the effect of TPO on progesterone, inhibin A and IGF-I. These results provide the first evidence that TPO may be a potent regulator of ovarian function (e.g. proliferation, apoptosis and the secretion of peptide hormones, steroids, growth factors and growth factor-binding protein, as well as of the expression of some intracellular messengers). Furthermore, they demonstrated the importance of PKA in controlling these functions and in mediating the effects of TPO on ovarian cells. It remains possible that other (TK- and Cdc2/p34-dependent) intracellular mechanisms are also involved in mediating TPO action on the ovary.



Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2911-2922 ◽  
Author(s):  
Mark J. McCabe ◽  
Gerard A. Tarulli ◽  
Sarah J. Meachem ◽  
David M. Robertson ◽  
Peter M. Smooker ◽  
...  

Sertoli cell tight junctions (TJs) are an essential component of the blood-testis barrier required for spermatogenesis; however, the role of gonadotropins in their maintenance is unknown. This study aimed to investigate the effect of gonadotropin suppression and short-term replacement on TJ function and TJ protein (occludin and claudin-11) expression and localization, in an adult rat model in vivo. Rats (n = 10/group) received the GnRH antagonist, acyline, for 7 wk to suppress gonadotropins. Three groups then received for 7 d: 1) human recombinant FSH, 2) human chorionic gonadotropin (hCG) and rat FSH antibody (to study testicular androgen stimulation alone), and 3) hCG alone (to study testicular androgen and pituitary FSH production). TJ proteins were assessed by real-time PCR, Western blot analysis, and immunohistochemistry, whereas TJ function was assessed with a biotin permeation tracer. Acyline treatment significantly reduced testis weights, serum androgens, LH and FSH, and adluminal germ cells (pachytene spermatocyte, round and elongating spermatids). In contrast to controls, acyline induced seminiferous tubule permeability to biotin, loss of tubule lumens, and loss of occludin, but redistribution of claudin-11, immunostaining. Short-term hormone replacement stimulated significant recoveries in adluminal germ cell numbers. In hCG ± FSH antibody-treated rats, occludin and claudin-11 protein relocalized at the TJ, but such relocalization was minimal with FSH alone. Tubule lumens also reappeared, but most tubules remained permeable to biotin tracer, despite the presence of occludin. It is concluded that gonadotropins maintain Sertoli cell TJs in the adult rat via a mechanism that includes the localization of occludin and claudin-11 at functional TJs.



2004 ◽  
Vol 16 (2) ◽  
pp. 231 ◽  
Author(s):  
A. Gonzalez-Bulnes ◽  
J. Santiago Moreno ◽  
R.M. Garcia-Garcia ◽  
C.J.H. Souza ◽  
A. Lopez-Sebastian ◽  
...  

In goats, as in other mammals, the use of treatment with GnRH antagonists (GnRHa) inhibits gonadotrophin secretion, causing a suppression of the growth of large ovarian follicles. Thus, GnRHa treatment could be useful to decrease the effects of dominant follicles prior to ovarian stimulation, increasing the number of gonadotrophin-responsive follicles at the start of FSH treatments and improving the ovarian response in terms of transferable embryos. However, in goats, the beneficial effects of this treatment is annulled by a high number of unfertilised ova and degenerated embryos (2003, Cognie et al., Theriogenology 59, 171–188), which suggests deficiencies in oocyte developmental competence per se or induced by endocrine or follicular alterations during the peri-ovulatory period. We have tested whether these failures can be related to a prolongation of gonadotrophin down-regulation and/or alterations in follicular function after cessation of the antagonist, during the period of administration of the superovulatory treatment, around 4 days after the end of GnRHa treatment. A total of 15 does received 45-mg FGA intravaginal sponges (Chronogest®, Intervet Int, H), the first group of 10 females were treated with daily injections of 0.5mg of the GnRHa Teverelix (Antarelix™, Zentaris, G) for 6 days from Day 5 of sponge insertion, while five does acted as controls receiving saline. Endocrine and ovarian function were monitored daily from Day −5 to Day 4 (Day 0=day of last GnRHa injection). Pituitary activity was determined by measuring plasma FSH and LH, and follicular activity by ultrasonographic monitoring of all &gt;2mm follicles and by assessing plasma inhibin A levels. During GnRH antagonist treatment, the mean plasma LH concentration was lower in treated than control goats (0.5±0.2 v. 0.7±0.5ng/mL, P&lt;0.0005); however, the FSH levels remained unaffected (0.8±0.4 v. 0.8±0.5ng/mL). In this period, treated does also showed an increase in the number of small follicles 2–3mm in size (10.7±0.7 v. 8.4±0.6, P&lt;0.05), and a decrease in both the number of follicles &gt;4mm in size (5.0±0.3 v. 6.8±0.5, P&lt;0.005) and the secretion of inhibin A (120.9±10.7 v. 151.6±12.6pg/mL, P&lt;0.05). After GnRHa treatment, LH levels increased in treated goats from the day after the last Teverelix injection (Day 1), so that LH levels were the same as controls on Day 3 (0.6±0.1 v. 0.6±0.2ng/mL). However, there were even greater numbers of small follicles than during the period of GnRHa treatment (15.4±0.6 in treated v. 8.9±0.7 in control, P&lt;0.0005). Moreover, the number of follicles &gt;4mm in size and the secretion of inhibin A remained lower in treated goats (3.9±0.3 follicles and 84.4±7.0pg/mL v. 5.4±0.5 follicles, P&lt;0.05 and 128.9±14.2pg/mL, P&lt;0.05). These results indicate that pituitary secretion of gonadotrophins is restored shortly after the end of GnRHa treatment, but the number of follicles and the secretion of inhibin A are affected. This may be relevant to the failures in ovulation and/or fertilization reported for superovulatory protocols with GnRHa pre-treatments in goats.



2012 ◽  
Vol 97 (9) ◽  
pp. E1766-E1773 ◽  
Author(s):  
Elbrich P. C. Siemensma ◽  
A. A. E. M. (Janielle) van Alfen-van der Velden ◽  
Barto J. Otten ◽  
Joop S. E. Laven ◽  
Anita C. S. Hokken-Koelega

Context: The etiology of hypogonadism in girls with Prader-Willi syndrome (PWS) remains uncertain. Objectives: The aim of the study was to evaluate gonadal function longitudinally in girls and female adolescents with PWS. Measurements: We performed a longitudinal assessment of anti-Müllerian hormone (AMH), gonadotropins, estradiol (E2), inhibin B and A, and pubertal development in girls and female adolescents with PWS. Patients and Methods: Sixty-one girls participating in the Dutch PWS Cohort study participated in the study. Serum AMH, gonadotropins, E2, and inhibin B and A levels were compared with reference values. Results: AMH levels in girls and female adolescents with PWS were comparable to reference levels between 6 months and 22 yr of age. From 10 yr of age, FSH and LH levels increased to above the 5th percentile compared to reference levels. E2 and inhibin B levels were in the low normal range in the majority, and inhibin A levels were low but detectable in almost half the female adolescents with PWS. The median age at puberty onset was comparable, but the median ages at attaining Tanner M3 (P = 0.05) and M4 (P &lt; 0.0001) were significantly higher in girls with PWS than in healthy references. Conclusion: Our study shows that the primordial follicle pool and number of small antral follicles are conserved in girls and female adolescents with PWS. We found no classical hypogonadotropic hypogonadism. However, maturation of follicles and progression of pubertal development are impaired, which might be due to dysregulation of LH secretion. Because these impairments are not absolute, ovulation and thus conception cannot be ruled out in individual female adolescents with PWS.



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