Regulation of gonadotrophin-releasing hormone receptor mRNA expression in the sheep

1994 ◽  
Vol 143 (1) ◽  
pp. 175-182 ◽  
Author(s):  
J Brooks ◽  
A S McNeilly
Keyword(s):  
Gnrh Agonist ◽  
Hormone Receptor ◽  
Luteal Phase ◽  
Gnrh Antagonist ◽  
Single Injection ◽  
Mrna Levels ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Oestradiol Production

Abstract To investigate the regulation of the sheep gonadotrophin-releasing hormone receptor (GnRH-R) gene expression, two different treatment regimes were used. Experiment 1 examined the effects of twice daily injections of ovine follicular fluid (oFF, 15 ml s.c.) as a source of inhibin, and daily GnRH antagonist injections (Nal-Glu.HOAc, 2 mg s.c.) on days 9–12 of the oestrous cycle. Luteolysis was induced on day 12 with prostaglandin (PG) and the ewes killed at two different stages; day 12 (luteal) and 18 h after PG injection. Experiment 2 examined the effect of a single injection of oestradiol benzoate (100 μg i.m.) 18 h before death in luteal phase ewes and ewes chronically implanted with the GnRH agonist, buserelin. In both experiments, pituitaries were removed at death for determination of pituitary GnRH binding, LH content and levels of GnRH-R and LHβ mRNA. In addition in experiment 1, follicles ≥2·5 mm were dissected from the ovaries for determination of oestradiol content. In experiment 1, oFF treatment during the luteal phase completely inhibited follicle oestradiol production but was without effect on the other parameters measured. After cessation of oFF treatment and induction of luteolysis, a significant (P<0·05) increase in plasma LH occurred but the normal follicular increase in both GnRH-R mRNA levels and GnRH binding seen in control ewes was prevented. GnRH antagonist treatment alone or in combination with oFF also inhibited follicle oestradiol production, prevented the increase in GnRH-R mRNA, completely inhibited GnRH binding and significantly decreased LHβ mRNA levels. Pituitary LH content was unaffected by any treatment. In experiment 2, oestradiol treatment did not affect GnRH-R mRNA levels, GnRH binding, LHβ mRNA or pituitary LH content in luteal phase ewes, whilst chronic GnRH agonist treatment acted to decrease these parameters dramatically. A single injection of oestradiol in the GnRH agonist treated ewes significantly (P<0·05) increased GnRH-R mRNA levels and completely restored GnRH binding to luteal levels, without any effect on LHβ mRNA or pituitary LH content. These results suggest that the control of GnRH receptor expression in the sheep is directly related to oestradiol and not to the action of GnRH itself. Journal of Endocrinology (1994) 143, 175–182

Suppression of pituitary-testis function in rats treated neonatally with a gonadotrophin-releasing hormone agonist and antagonist: acute and long-term effects

1989 ◽  
Vol 123 (1) ◽  
pp. 83-91 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi
Keyword(s):  
Body Weight ◽  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Long Term Effects ◽  
Adult Rats ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Accessory Sex Organs ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91

Relationship between gonadotrophin subunit gene expression, gonadotrophin-releasing hormone receptor content and pituitary and plasma gonadotrophin concentrations during the rebound release of FSH after treatment of ewes with bovine follicular fluid during the luteal phase of the cycle

1992 ◽  
Vol 8 (2) ◽  
pp. 109-118 ◽  
Author(s):  
J. Brooks ◽  
W. J. Crow ◽  
J. R. McNeilly ◽  
A. S. McNeilly
Keyword(s):  
Follicular Fluid ◽  
Luteal Phase ◽  
Gnrh Receptor ◽  
Mrna Levels ◽  
Α Subunit ◽  
Luteal Regression ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion ◽  
Cessation Of Treatment

ABSTRACT The modulation of FSH secretion at the beginning and middle of the follicular phase of the cycle represents the key event in the growth and selection of the preovulatory follicle. However, the mechanisms that operate within the pituitary gland to control the increased release of FSH and its subsequent inhibition in vivo remain unclear. Treatment of ewes with bovine follicular fluid (bFF) during the luteal phase has been previously shown to suppress the plasma concentrations of FSH and, following cessation of treatment on day 11, a rebound release of FSH occurs on days 12 and 13. When luteal regression is induced on day 12, this hypersecretion of FSH results in an increase in follicle growth and ovulation rate. To investigate the mechanisms involved in the control of FSH secretion, ewes were treated with twice daily s.c. injections of 5 ml bFF on days 3–11 of the oestrous cycle and luteal regression was induced on day 12 with prostaglandin (PG). The treated ewes and their controls were then killed on day 11 (luteal), or 16 or 32h after PG and their pituitaries removed and halved. One half was analysed for gonadotrophin and gonadotrophin-releasing hormone (GnRH) receptor content. Total pituitary RNA was extracted from the other half and subjected to Northern analysis using probes for FSH-β, LH-β and common α subunit. Frequent blood samples were taken and assayed for gonadotrophins. FSH secretion was significantly (P<0.01) reduced during bFF treatment throughout the luteal phase and then significantly (P<0.01) increased after cessation of treatment, with maximum secretion being reached 18– 22h after PG, and then declining towards control values by 32h after PG. A similar pattern of LH secretion was seen after bFF treatment. Pituitary FSH content was significantly (P<0.05) reduced by bFF treatment at all stages of the cycle. No difference in the pituitary LH content was seen. The increase in GnRH receptor content after PG in the controls was delayed in the treated animals. Analysis of pituitary mRNA levels revealed that bFF treatment significantly (P<0.01) reduced FSH-β mRNA levels in the luteal phase. Increased levels of FSH-β, LH-β and α subunit mRNA were seen 16h after PG in the bFF-treated animals, at the time when FSH and LH secretion from the pituitary was near maximum. These results suggest that the rebound release of FSH after treatment with bFF (as a source of inhibin) is related to a rapid increase in FSH-β mRNA, supporting the concept that the rate of FSH release is directly related to the rate of synthesis.

A gonadotrophin-releasing hormone (GnRH) antagonist inhibits GnRH- but not LH-induced meiosis in follicle-enclosed rat oocytes in vitro

1982 ◽  
Vol 101 (2) ◽  
pp. 264-267 ◽  
Author(s):  
C. Ekholm ◽  
T. Hillensjö ◽  
W. J. Le Maire ◽  
C. Magnusson ◽  
C. S. Sheela Rani
Keyword(s):  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Similar Response ◽  
Releasing Hormone ◽  
Lactate Accumulation ◽  
Receptor Sites ◽  
Gonadotrophin Releasing Hormone ◽  
Stimulation Of

Abstract. Previous studies have shown that gonadotrophin-releasing hormone (GnRH) can induce resumption of meiosis in follicle-enclosed rat oocytes. In the present study a GnRH antagonistic analogue ([d-pGlul, d-Phe2,-d-Trp3,6]LRF) was found to effectively abolish the stimulatory effect of a GnRH agonist upon resumption of meiosis and lactate accumulation in isolated pre-ovulatory rat follicles but the have no effect on LH stimulation of these parameters. It is concluded that although LH and GnRH can evoke a similar response they act through separate receptor sites and that it is unlikely that GnRH mediates the effect of LH on meiosis or glycolysis.

Effect of gonadotrophin-releasing hormone agonist-induced suppression of LH and FSH on follicle growth and corpus luteum function in the ewe

1987 ◽  
Vol 115 (2) ◽  
pp. 273-282 ◽  
Author(s):  
A. S. McNeilly ◽  
H. M. Fraser
Keyword(s):  
Continuous Infusion ◽  
Corpus Luteum ◽  
Gnrh Agonist ◽  
Luteal Phase ◽  
Plasma Concentrations ◽  
Follicular Development ◽  
Similar Proportion ◽  
Simple Method ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Continuous infusion of a gonadotrophin-releasing hormone (GnRH) agonist (buserelin) by osmotic minipump from day 1 of the luteal phase in five Welsh ewes resulted in a sustained suppression of plasma concentrations of FSH which increased three- to eightfold within 2 days after the end of infusion 29 days later. Plasma concentrations of LH increased three- to eightfold over the first 5 days of infusion and then became basal and non-pulsatile until 1 day after the end of infusion. Duration of the luteal phase and plasma concentrations of progesterone were not significantly different in control and treated ewes. Pulses of LH in control ewes were followed by increases in concentrations of progesterone in samples collected at 10-min intervals for 7 h on days 10 and 14 of the luteal phase. However, progesterone was also released in a pulsatile manner in the absence of LH pulses in both control and GnRH agonist-treated ewes. After natural luteolysis, no ovulation or corpus luteum function occurred in treated ewes up to 15 days after the end of treatment on day 29, even though oestrus, indicating follicular development and oestrogen secretion, had occurred 8–11 days after treatment ended. After 30 days of infusion the ovaries of GnRH agonist-treated ewes contained no follicles > 2·5 mm in diameter. In follicles of 1–2 mm in diameter the basal and LH-stimulated production of oestradiol and testosterone in vitro were similar in both control and GnRH agonist-treated ewes, and a similar proportion of these follicles was oestrogenic (> 370 mol oestradiol per follicle) in GnRH agonist-treated and control ewes. These results show (1) that progesterone secretion by the corpus luteum of the ewe can be sustained in the presence of basal concentrations but absence of pulsatile secretion of LH, and progesterone is released in a pulsatile manner whether or not LH pulses are present, (2) that follicular development beyond 2·5 mm in diameter in the ewe is dependent upon adequate stimulation by both LH and FSH and (3) that the continuous infusion of GnRH agonist is a simple method for providing reproducible suppression of LH and FSH and follicular development in the ewe to allow the study of gonadotrophin action on the ovary in vivo. J. Endocr. (1987) 115, 273–282

Gonadotrophin-releasing hormone modulation of gonadotrophins in the ewe: evidence for differential effects on gene expression and hormone secretion

1991 ◽  
Vol 7 (1) ◽  
pp. 35-43 ◽  
Author(s):  
J. R. McNeilly ◽  
P. Brown ◽  
A. J. Clark ◽  
A. S. McNeilly
Keyword(s):  
Gene Expression ◽  
Gnrh Agonist ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Mrna Levels ◽  
Β Subunit ◽  
Subunit Gene ◽  
Α Subunit ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone

ABSTRACT While the regulation of gonadotrophin secretion by gonadotrophin-releasing hormone (GnRH) has been well documented in both rats and sheep, its role in the synthesis of gonadotrophin subunits remains unclear. We have investigated the effects of the specific inhibition of GnRH by a GnRH agonist on the expression of gonadotrophin subunit genes and the subsequent storage and release of both intact hormones and free α subunit. Treatment with GnRH agonist for 6 weeks abolished pulsatile LH secretion, reduced plasma concentrations of FSH and prevented GnRH-induced release of LH and FSH. This was associated with a reduction of pituitary LH-β mRNA and FSH-β mRNA levels (to 5 and 30% of luteal control values respectively), but not α mRNA which was significantly increased (75% above controls). While there was a small decrease in the pituitary content of FSH (30% of controls), there was a drastic reduction in LH pituitary content (3% of controls). In contrast to the observed rise in α mRNA, there was a decrease in free α subunit in both the pituitary and plasma (to 30 and 80% of control levels). These results suggest that, while GnRH positively regulates the expression of both gonadotrophin β-subunit genes, it can, under certain circumstances, negatively regulate α-subunit gene expression. Despite the complete absence of LH and FSH in response to GnRH, there remained a basal level of β-subunit gene expression and only a modest reduction (50%) in the plasma levels of both FSH and LH, suggesting that there is a basal secretory pathway. The dramatic reduction in LH pituitary content indicates that GnRH is required for the operation of a regulatory/storage pathway for the secretion of LH. There appears to be no similar mechanism for FSH. The LH-specific pathway is probably dependent upon the availability of LH-β subunits which subsequently plays a role in regulating α subunit by sequestering, assembling and storing the intact hormone in the presence of GnRH. Finally, in the absence of responsiveness to GnRH, the regulation of α-subunit production is not at the level of gene transcription. Inefficient translation of the mRNA or rapid degradation of the free α chain may account for the observed dramatic decrease in production of α subunit.

Control of the koala (Phascolarctos cinereus) anterior pituitary-gonadal axis with analogues of GnRH

2008 ◽  
Vol 20 (5) ◽  
pp. 598 ◽  
Author(s):  
Camryn D. Allen ◽  
Michelle Burridge ◽  
Mandy L. Chafer ◽  
Vere N. Nicolson ◽  
Sophia C. Jago ◽  
...  
Keyword(s):  
Gnrh Agonist ◽  
Anterior Pituitary ◽  
Luteal Phase ◽  
Gnrh Antagonist ◽  
Cell Function ◽  
Phascolarctos Cinereus ◽  
Natural Sequence ◽  
Dose Rates ◽  
Anterior Pituitary Function ◽  
Gonadotrophin Releasing Hormone

The aim of the present study was to determine whether analogues of gonadotrophin-releasing hormone (GnRH) could be used to both induce an acute testosterone response and suppress anterior pituitary function in male koalas, and induce a luteal phase in female koalas. Experiment 1 characterised the steroidogenic response of male koalas to administration of 30 μg (4.3 μg kg–1) natural-sequence GnRH. Intra-muscular injection of natural-sequence GnRH induced the release of LH and testosterone with peak concentrations at 30 min (3.7 ± 1.9 ng mL–1) and 2 h (5.4 ± 0.5 ng mL–1), respectively. In Experiment 2, a single injection of the GnRH antagonist acyline (100 μg (14.3 μg kg–1) or 500 μg (71.4 μg kg–1)) did not influence the testosterone response to subsequent injections of natural-sequence GnRH. In Experiment 3, 4 μg (~0.67 μg kg–1) of the GnRH agonist buserelin induced a luteal phase in five female koalas based on a LH surge, secretion of progestogen, and a normal-length oestrous cycle. The findings have shown that (1) natural-sequence GnRH can be used to test gonadotroph cell function and determine the testosterone-secreting capacity of male koalas, (2) the GnRH antagonist, acyline, at the dose rates used, does not suppress the pituitary-testis axis in male koalas, and (3) the GnRH agonist, buserelin, induces a normal luteal phase in female koalas.

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