GnRH antagonist inhibition of gonadotropin and steroid secretion in boars in vivo and steroid production in vitro.

2000 ◽  
Vol 78 (6) ◽  
pp. 1591 ◽  
Author(s):  
E L Zanella ◽  
D D Lunstra ◽  
T H Wise ◽  
J E Kinder ◽  
J J Ford
Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 147-154 ◽  
Author(s):  
Claudio Parra ◽  
Jenny L Fiedler ◽  
S Leticia Luna ◽  
Monika Greiner ◽  
Vasantha Padmanabhan ◽  
...  

Vasoactive intestinal polypeptide (VIP) stimulates estradiol and progesterone release from ovarian granulosa cells in vitro. Very little information is available as to the role VIP plays in the control of steroid secretion during reproductive cyclicity and in ovarian pathologies involving altered steroid secretion. In this study, we determined the involvement of VIP in regulating ovarian androgen and estradiol release during estrous cyclicity and estradiol valerate (EV)-induced polycystic ovarian development in rats. Our findings show that androgen and estradiol release from ovaries obtained during different stages of rat estrous cycle mimic cyclic changes in steroid release observed in vivo with maximal release occurring during late proestrus. VIP increased androgen release from ovaries of all cycle stages except late proestrus and estradiol release from all cycle stages. Increases in VIP-induced androgen and estradiol release were maximal at early proestrus. Inclusion of saturating concentrations of androstenedione increased magnitude of VIP-induced estradiol release at diestrus and estrus but not proestrus. Magnitude of VIP-induced androgen and estradiol release tended to be greater in the ovaries from EV-treated rats with polycystic ovary compared with estrous controls. At the tissue level, ovarian VIP concentration was cycle stage dependent with highest level seen in diestrus. Maximum concentration of VIP was found in EV-treated rats. Changes in VIP were inversely related to changes in ovarian nerve growth factor, a neuropeptide involved in ovarian androgen secretion. These results strongly suggest that intraovarian VIP participates in the control of estradiol secretion during the rat estrous cycle and possibly in the maintenance of increased ovarian estradiol secretory activity of EV-treated rats.


1983 ◽  
Vol 104 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Paul V. Holmes ◽  
Per O. Janson ◽  
Jan Sogn ◽  
Björn Källfelt ◽  
William J. LeMaire ◽  
...  

Abstract. Both ovaries of 31 rabbits were perfused with a chemically defined medium in vitro in a recirculation system. In one series of experiments, hCG (100 IU) was injected iv 5–6 h prior to anaesthesia and surgery. Approximately 1 h later the perfusion was started. One ovary was perfused as control while the other ovary was perfused with 5 μg/ml indomethacin or with indomethacin and 1 μg/ml PGF2α. In another series of experiments the rabbits received no pretreatment prior to operation. Instead, bovine LH was added to the perfusion medium of both control and experimental ovaries. The experimental side also received either indomethacin or indomethacin and PGF2α. Finally, the effect of PGF2α in the absence of LH was compared to the control ovary receiving only LH. After injection of hCG in vivo, ovulations occurred in 4 of 5 control ovaries. Indomethacin completely blocked ovulation in 4 of the 5 ovaries treated, while PGF2α restored ovulations in all the experimental ovaries. In the group of experiments where LH was added in vitro, ovulations were induced in all ovaries treated with varying LH doses. Furthermore, indomethacin blocked ovulation in 5 out of 7 ovaries, and PGF2α restored ovulation in all ovaries. Fifty per cent of the ovaries treated only with PGF2α (in the absence of LH) also ovulated. The pattern of steroid release did not differ between control ovaries, indomethacin treated ovaries, and indomethacin + PGF2α treated ovaries. Ovaries treated in perfusion with PGF2α alone had very low steroid levels compared to the ovaries treated with LH. This study confirms that indomethacin blocks ovulation in the perfused rabbit ovary and that this blockade can be overcome by exogenous PGF2α. Indomethacin and PG-treatments after ovulation induction did not affect ovarian steroidogenesis. Furthermore, while PGF2α was able to induce ovulations in these perfused oestrous ovaries in the absence of LH, it did not stimulate steroidogenesis.


1989 ◽  
Vol 120 (3) ◽  
pp. 308-314
Author(s):  
A. M. Ultee-van Gessel ◽  
G.J. van Steenbrugge ◽  
F. G. Leemborg ◽  
F. H. Schroeder ◽  
F. H. de Jong

Abstract. The potent luteinizing hormone-releasing hormone antagonist [N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]GnRH (4 mg/kg) was administered sc once or daily for 21 days to immune-deficient (nude) and normal immune-competent (NIC) male mice derived from the same genetic background. Effects of in vivo pretreatment with the antagonist on gonadotropin secretion from hemipituitary glands from both types of mice were studied in vitro in the presence or absence of synthetic GnRH. Treatment with the GnRH antagonist caused differential effects on release of FSH and LH from and amounts of FSH and LH in hemipituitary glands. Pituitary FSH secretion was effectively inhibited, whereas effects on pituitary LH were less evident or nonsignificant under these experimental conditions. Long-term treatment with the antagonist caused larger effects on pituitary secretion and content of FSH, when compared with short-term treatment. No significant effects of duration of treatment on secretion or pituitary content of LH were detected. Addition of synthetic GnRH to the incubation medium caused stimulation of gonadotropin release. Therefore, it was concluded that the high doses of this GnRH antagonist were not able to block GnRH receptors effectively in the pituitary glands of nude and NIC male mice. The incomplete suppression of LH secretion by this high dose of the GnRH antagonist may partly explain the inability of the antagonist to suppress plasma testosterone levels and the growth of androgen-dependent tumours in male mice.


1988 ◽  
Vol 16 (03n04) ◽  
pp. 93-105 ◽  
Author(s):  
Satoshi Usuki

The effect of Hachimijiogan (HZ) and Keishibukuryogan (KB) on the steroid production in rats was examined in vivo and in vitro. In an in vivo study, HZ stimulated the testes from ten-week old male rats to produce testoterone, whereas KB decreased the tissue testosterone concentrations. The Δ4-androstenedione and estradiol-17β (E2) showed no significant changes. In an incubation study, HZ also stimulated the testosterone production. The data suggested that HZ produces testosterone in rat testes. The role of KB is questionable.


2002 ◽  
Vol 50 (1) ◽  
pp. 79-92 ◽  
Author(s):  
Annett Bellmann ◽  
F. Schneider ◽  
W. Kanitz ◽  

In the following investigations, the LH secretion of cells from pituitaries in heifers on days 16-18 of their oestrous cycle (n = 14) was analysed. Cells were dissociated with trypsin and collagenase and maintained in a static culture system. For the estimation of LH release, the cells were incubated with various concentrations of mammalian GnRH (Lutrelef) for 6h. To determine the action of Antarelix (GnRH antagonist), the cells were preincubated for 1 h with concentrations of 10-5 or 10-4 M Antarelix followed by 10-6 M GnRH coincubation for a further 6h. At the end of each incubation, the medium was collected for LH analysis. Parallel, intracellular LH was qualitatively detected by immunocytochemistry. Changes in the intensity of LH staining within the cells in dependence of different GnRH concentrations were not observed, but a significant increase LH secretion in pituitary cells was measured at 10-6 M GnRH. Antarelix had no effect on basal LH secretion at concentrations of 10-4 and 10-5 M. After coincubation of pituitary cells with Antarelix and GnRH, Antarelix blocked the GnRH-stimulated LH secretion with a maximal effect of 10-4 M, but the staining of immunoreactive intracellular LH was detected at approximately the same level compared to the pituitary cells treated with exogenous GnRH alone. These data demonstrate that Antarelix is effective in influencing the GnRH-stimulated LH secretion of pituitary cells in vitro. After administration of Antarelix in vivo, the GnRH-stimulated LH secretion of cultured pituitary cells was not inhibited.


1977 ◽  
Vol 73 (1) ◽  
pp. 59-65 ◽  
Author(s):  
E. V. YOUNGLAI

SUMMARY Follicles were isolated from rabbits before and after mating and the effects of LH on steroidogenesis were studied using an incubation technique. Before mating testosterone was the major steroid produced in response to LH. Mating or administration of ovine LH in vivo caused the follicles to produce mainly progesterone and these follicles were refractory to LH in vitro. Up to 72 h after mating, LH would stimulate follicles to produce progesterone. At 96 h after mating, the testosterone response to LH was again manifest. These results suggest that the responsiveness of rabbit follicles to LH is dependent on the endocrine status of the animal when the ovaries were removed.


2001 ◽  
pp. 677-685 ◽  
Author(s):  
JM Weiss ◽  
K Oltmanns ◽  
EM Gurke ◽  
S Polack ◽  
F Eick ◽  
...  

OBJECTIVE: GnRH antagonists have recently been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). We have here investigated whether the GnRH antagonists cetrorelix and ganirelix exert effects on ovarian steroidogenesis. Since there is some controversy about the action of GnRH agonists in the human ovary we also tested the effect of triptorelin on steroid production in cultured human granulosa lutein cells. METHODS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin, cetrorelix, ganirelix or no GnRH analogue. RESULTS: Such in vivo treatment did not result in significant effects of triptorelin or the two GnRH antagonists on spontaneous or human chorionic gonadotropin (hCG)-stimulated steroidogenesis. To exclude the possibility that the in vivo treatment might not affect in vitro steroid production because of low or absent peptide activity, we performed in vitro treatments with triptorelin, cetrorelix and ganirelix for up to 96 h. However, these treatment paradigms did not influence basal or hCG-stimulated steroid production. CONCLUSIONS: We conclude that GnRH antagonists do not exert any significant effects on ovarian steroidogenesis in vitro and therefore their introduction into protocols of COH is unlikely to impair ovarian function.


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