Effects of a novel gonadotropin-releasing hormone antagonist (ORG 30850) on gonadotropin and prolactin secretion by rat pituitary cells in culture

1991 ◽  
Vol 124 (1) ◽  
pp. 98-106 ◽  
Author(s):  
Paul Franchimont ◽  
Sabine M. Almer ◽  
Chantal-J. Charlet-Renard ◽  
Christine L. Daubresse ◽  
Peter P. Kicovic

Abstract. The effect of a new GnRH antagonist (ORG 30850 ANT) on FSH, LH, and PRL secretion was studied using male rat pituitary cells in monolayer cell culture. In the absence of GnRH, ORG 30850 ANT did not alter spontaneous FSH and LH secretion into culture medium or the cell content of these hormones. In the presence of GnRH (10−8 mol/l), ORG 30850 ANT significantly and dose-dependently inhibited FSH and LH secretion into culture medium while increasing their cell content. Conversely, in the presence of a single dose of ORG 30850 ANT, FSH and LH secretion rose significantly when subjected to increasing amounts of GnRH, whereas the hormonal cell content diminished. Furthermore, inhibition of GnRH-induced FSH and LH release by ORG 30850 ANT was not changed by pre-incubation with the GnRH antagonist regardless of the pre-incubation time. The inhibitory effect of the GnRH antagonist was observed early, with its peak occurring within 6 h of culture. These short-term studies indicate that ORG 30850 ANT specifically inhibits GnRH-induced gonadotropin release into culture medium, exerts no effect on the rate of gonadotropin production in the presence or absence of GnRH, competitively and reversibly inhibits the binding of natural GnRH to its receptors, and does not lead to any modifications in PRL secretion.

1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S188-S189
Author(s):  
L. KIESEL ◽  
T. RABE ◽  
D. SCHOLZ ◽  
V. KIRSCHNER ◽  
B. RUNNEBAUM

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 558
Author(s):  
ZeWen Yu ◽  
WenZhi Ren ◽  
Tian Wang ◽  
WeiDi Zhang ◽  
ChangJiang Wang ◽  
...  

CircRNAs have been identified to be expressed differently and stably in numerous species and tissues, but their functions in growth hormone (GH) secretion are still largely unknown. In summary, we have revealed a circRNA-miRNA-mRNA network that may play a biological role in the rat pituitary gland. First, we verified the chromosome location information of circAgtpbp1 according to sequencing analysis. The circAgtpbp1 characteristics were authenticated through PCR, qRT–PCR, treating with RNase and fluorescent in situ hybridization (FISH). Second, we detected the expression pattern of circAgtpbp1 in the rat anterior pituitary by qRT–PCR. We also designed circAgtpbp1 siRNA and constructed overexpression plasmid to evaluate the effect of circAgtpbp1 function on GH secretion by qRT–PCR, ELISA and Western blot. CircAgtpbp1 is a stable, truly circular molecule. We found that circAgtpbp1 interacted with miR-543-5p and can regulate GH secretion in pituitary cells through a circAgtpbp1-miR-543-5p-GH axis. Overall, the evidence generated by our study suggests that circAgtpbp1 can act as a sponge of miR-543-5p to reduce the inhibitory effect of miR-543-5p on Gh1 and further promote GH secretion. These findings expand our existing knowledge on the mechanisms of hormone regulation in the pituitary gland.


1980 ◽  
Vol 87 (1) ◽  
pp. 95-103 ◽  
Author(s):  
G. DELITALA ◽  
T. YEO ◽  
ASHLEY GROSSMAN ◽  
N. R. HATHWAY ◽  
G. M. BESSER

The inhibitory effects of dopamine and various ergot alkaloids on prolactin secretion were studied using continuously perfused columns of dispersed rat anterior pituitary cells. Bromocriptine (5 nmol/l) and lisuride hydrogen maleate (5 nmol/l) both inhibited prolactin secretion, the effects persisting for more than 3 h after the end of the administration of the drugs. A similar although less long-lasting effect was observed with lergotrile (50 nmol/l) and the new ergoline derivative, pergolide (5 nmol/l). These effects contrasted with the rapid disappearance of the action of dopamine. The potency estimates of the ergots relative to that of dopamine were: lergotrile, 2·3; bromocriptine, 13; lisuride, 15; pergolide, 23. The dopamine-receptor blocking drugs, metoclopramide and haloperidol, antagonized the prolactin release-inhibiting activity of the compounds; bromocriptine and lisuride showed the highest resistance to this dopaminergic blockade. The results suggested that the direct effect of the ergot derivatives on dispersed pituitary cells was mediated through dopamine receptors and emphasized the long-lasting action of bromocriptine and lisuride in vitro.


1988 ◽  
Vol 47 (4) ◽  
pp. 323-328 ◽  
Author(s):  
Mireille Rabier ◽  
Claude Chavis ◽  
André Crastes de Paulet ◽  
Marcelle Damon

1992 ◽  
Vol 70 (7) ◽  
pp. 963-969 ◽  
Author(s):  
Gabriela T. Pérez ◽  
Marta E. Apfelbaum

The purpose of the present experiments was to examine the short- and long-term effects of estradiol-17β (E2), progesterone (P), and 5α-dihydrotestosterone (DHT), alone and in combination, on the gonadotrophin-releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion, using an ovariectomized rat pituitary cells culture model. After 72 h in steroid-free medium, pituitary cells were further cultured for 24 h in medium with or without E2 (1 nM), P (100 nM), or DHT (10 nM). Cultures were then incubated for 5 h in the absence or presence of 1 nM GnRH with or without steroids. LH was measured in the medium and cell extract by radioimmunoassay. The results show that the steroid hormones exert opposite effects on the release of LH induced by GnRH, which seems to be dependent upon the length of time the pituitary cells have been exposed to the steroids. In fact, short-term (5 h) action of E2 resulted in a partial inhibition (64% of control) of LH release in response to GnRH, while long-term (24 h) exposure enhanced (158%) GnRH-induced LH release. Similar results were obtained with DHT, although the magnitude of the effect was lower than with E2. Conversely, P caused an acute stimulatory action (118%) on the LH released in response to GnRH and a slightly inhibitory effect (90%) after chronic treatment. GnRH-stimulated LH biosynthesis was also influenced by steroid treatment. Significant increases in total (cells plus medium) LH were observed in pituitary cells treated with E2 or DHT. While the stimulatory effect of E2 was evident after both acute (133%) and chronic (119%) treatment, that of DHT appears to be exerted mainly after long-term priming (118%). These results suggest that the steroids modulate GnRH-induced LH secretion by acting on both synthesis and release of LH. On the other hand, total hormone content was not affected by P. The acute (5 h) effects of E2, P, and DHT on the GnRH response in E2-primed (24 h) cells during a short-term incubation, were also tested. Addition of P to the pituitary cells primed with E2 led to an acute potentiation of the stimulatory effect of E2 on GnRH-induced LH release and total content. Conversely, the augmentative E2 effect on pituitary responsiveness to GnRH was abolished by DHT. Taken together, these findings suggest that the physiological significance of the stimulatory action of progesterone could be to define the final magnitude of the LH preovulatory surge, while the inhibition by DHT could be required to limit the LH surge to that day of proestrus.Key words: luteinizing hormone, gonadotrophin-releasing hormone, steroid hormones, cultured pituitary cells.


1989 ◽  
Vol 50 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Steven W. Lamberts ◽  
Joke Zuyderwijk ◽  
Fred den Holder ◽  
Peter van Koetsveld ◽  
Leo Hofland

1999 ◽  
Vol 161 (3) ◽  
pp. 375-382 ◽  
Author(s):  
S Miyamoto ◽  
M Irahara ◽  
K Ushigoe ◽  
A Kuwahara ◽  
H Sugino ◽  
...  

We investigated the effect of activin A on secretion of LH, FSH, and prolactin (PRL) by female cultured rat pituitary cells at the single-cell level by means of the cell immunoblot assay. Anterior pituitary cells from 8-week-old female rats were preincubated with or without activin A for 24 h, after which they were monodispersed and immediately used for cell immunoblot assay. The percentages of LH-, FSH- and PRL-immunoreactive cell blots detected were 5.5, 5.3 and 43.1%, respectively, of all pituitary cells applied to the transfer membrane. The percentage of LH-secreting cells and mean LH secretion per cell did not change after treatment with activin. In contrast, activin significantly increased the percentage of FSH-secreting cells and mean FSH secretion per cell to 136.0 and 114. 5% respectively. In addition, activin significantly decreased the percentage of PRL-secreting cells and mean PRL secretion per cell to 52.2 and 72.0% respectively. These results suggest that (1) activin A has effects on female rat pituitary cells that increase not only the amount of FSH secretion per cell but also the number of FSH-secreting cells, and (2) activin A decreases both the amount of PRL secretion per cell and the number of PRL-secreting cells.


1985 ◽  
Vol 248 (5) ◽  
pp. C510-C519 ◽  
Author(s):  
J. J. Enyeart ◽  
T. Aizawa ◽  
P. M. Hinkle

Three dihydropyridine (DHP) Ca2+ antagonists were compared with several other organic Ca2+ antagonists with respect to their ability to inhibit depolarization-dependent hormone secretion from the GH4C1 pituitary cell line and from normal rat pituitary cells. The three DHP, nimodipine, nisoldipine, and nifedipine, potently and specifically inhibited KCl-stimulated prolactin secretion from GH4C1 cells (estimated IC50 values: 1.8, 1.8, and 6.0 nM, respectively). Both basal and thyrotropin-releasing hormone-stimulated secretion from GH4C1 cells were much less sensitive to inhibition by the DHP. The inhibition by the DHP was reversible, and their potency was independent of depolarizing concentrations of KCl between 18.8 and 53.8 mM. Other organic antagonists, including verapamil, cinnarizine, and diltiazem, blocked secretion from GH4C1 cells but at much higher concentrations. The estimated IC50 values for these three were 1,000, 1,100, and 3,500 nM, respectively. Depolarization-stimulated prolactin secretion from normal pituitaries was inhibited by the DHP and verapamil at the same concentrations found effective in GH4C1 cells. KCl-stimulated 45Ca2+ uptake by GH4C1 cells was also blocked by DHP at concentrations that inhibited secretion. Since depolarization-stimulated secretion and 45Ca2+ uptake are probably triggered by Ca2+ entering through voltage-sensitive channels, the above results suggest that DHP antagonists potently block these channels in both normal and transformed pituitary cells. These Ca2+ channels appear to be identical in this respect. These findings further suggest a similarity between the Ca2+ channels of endocrine cells and those of smooth muscle and other excitable cells.


1984 ◽  
Vol 107 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Janet E. Merritt ◽  
Stephen Tomlinson ◽  
Barry L. Brown

Abstract. The effect of flunarizine on the secretion of prolactin from monolayer cultures of normal rat pituitary cells has been determined. Both basal and TRHstimulated secretion were found to be significantly inhibited by micromolar concentrations of flunarizine, whereas depolarization (high K+)-stimulated secretion was virtually unaffected. These results indicate that TRH-stimulated prolactin secretion probably involves calcium influx and that flunarizine may be useful as a probe for particular Ca2+ channels.


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