scholarly journals Effects of a long-acting gonadotrophin-releasing hormone agonist (Leuprolide) on ovarian follicular development in prepubertal heifer calves

1994 ◽  
Vol 74 (4) ◽  
pp. 649-656 ◽  
Author(s):  
A. C. O. Evans ◽  
N. C. Rawlings
Keyword(s):  
Gnrh Agonist ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
Follicular Growth ◽  
Long Term Effects ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone ◽  
Ovarian Follicular Development ◽  
Ovarian Follicular Growth

We studied the effects of reducing gonadotrophin secretion on ovarian follicular development in young prepubertal heifer calves. Calves received a GnRH agonist (n = 5, 15 mg of Leuprolide acetate, i.m.) or carrier (n = 5) at 8 and 12 w of age. Starting at 8 and 34 w of age, ovarian follicles were monitored daily for 17 d, and at 10, 15, 25 and 35 w of age, blood samples were collected every 15 min for 12 h for measurement of serum concentration of LH and FSH. GnRH agonist treatment did not affect the age and body weight at puberty (P > 0.05). Agonist treatment suppressed follicle numbers and in two heifers follicle emergence (growth above 4–5 mm) was blocked immediately. In three agonist-treated heifers, follicle emergence was blocked after one extended wave of follicular growth. At 34 w of age the pattern of ovarian follicular growth did not differ between groups but oestradiol secretion was lower in agonist-treated heifers. During agonist treatment basal and mean concentrations of FSH, and LH and FSH pulse amplitude were decreased but basal LH concentrations increased (P < 0.05). At 25 and 35 w of age some rebound in gonadotrophin secretion was seen.We concluded that disrupting gonadotrophin secretion in young prepubertal heifer calves by GnRH agonist treatment, suppressed ovarian follicular growth but that a rebound in gonadotrophin secretion prevented long term-effects on sexual development. Key words: Follicle stimulating hormone, gonadotrophin-releasing hormone, heifer calves, luteinising hormone ovarian follicles

Long-term effects of a gonadotrophin-releasing hormone agonist ([d-Ser(But)6]GnRH(1–9)nonapeptide-ethylamide) on gonadotrophin secretion from human pituitary gonadotroph cell adenomas in vitro

1988 ◽  
Vol 118 (3) ◽  
pp. 491-496 ◽  
Author(s):  
M. Daniels ◽  
P. Newland ◽  
J. Dunn ◽  
P. Kendall-Taylor ◽  
M. C. White
Keyword(s):  
Gnrh Agonist ◽  
In Vitro Release ◽  
Long Term Effects ◽  
Human Pituitary ◽  
Α Subunit ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone

ABSTRACT We have studied the effects of TRH and native gonadotrophin-releasing hormone (GnRH), and of a GnRH agonist (Buserelin; [d-Ser(But)6]GnRH(1–9) nonapeptide-ethylamide), on LH, FSH, α subunit and LH-β subunit secretion from three human gonadotrophin-secreting pituitary adenomas in dispersed cell culture. During a 24 h study, treatment with 276 nmol TRH/1 resulted in a significant (P < 0·05) stimulated release of FSH and α subunit from all three adenomas, and LH from the two adenomas secreting detectable concentrations of this glycoprotein; treatment with 85 nmol GnRH/l significantly (P < 0·05) stimulated the release of α subunit from all three, but FSH from only two and LH from only one adenoma. During a long-term 28-day study, basal FSH and α subunit concentrations were maintained, but secretion of LH, and LH-β (detectable from one tumour only), declined with time from two of the three adenomas. Addition of Buserelin to the cultures resulted in the continuous (P < 0·05) stimulation of α subunit secretion from all three adenomas, and of LH and FSH from two, whilst a transient stimulatory effect on LH and FSH secretion was seen from a third adenoma, with subsequent secretion rates declining towards control values. These data show that human gonadotrophin-secreting adenomas demonstrate variable stimulatory responses to hypothalamic TRH and GnRH, and that during chronic treatment with a GnRH agonist the anticipated desensitizing effect of the drug was not observed in two out of three adenomas studied. The mechanism for this is not clear, but such drugs are unlikely to be of therapeutic value in the management of gonadotrophin-secreting tumours. The data also suggest that GnRH and GnRH agonists have a differential effect on the in-vitro release of intact gonadotrophins and the common α subunit. J. Endocr. (1988) 118, 491–496

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

Effect of basal and pulsatile LH release on FSH-stimulated follicle growth in ewes chronically treated with gonadotrophin-releasing hormone agonist

1991 ◽  
Vol 128 (3) ◽  
pp. 449-456 ◽  
Author(s):  
H. M. Picton ◽  
A. S. McNeilly
Keyword(s):  
Gnrh Agonist ◽  
Follicular Development ◽  
Follicle Growth ◽  
Releasing Hormone ◽  
Normal Number ◽  
Stage Of Development ◽  
Normal Diameter ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Follicular Response

ABSTRACT Ewes chronically treated with gonadotrophin-releasing hormone (GnRH) agonist were used to investigate the importance of the peripheral concentration of LH in FSH-stimulated follicular development. Twenty-four Welsh Mountain ewes were treated with two agonist implants containing 3·3 mg buserelin. During week 6 of treatment all the ewes were given a 72-h continuous infusion of ovine FSH alone (3 μg/h) or FSH with large (7·5 μg)- or small (2·5 μg) amplitude pulses of ovine LH delivered at 4-hourly intervals. The importance of baseline LH throughout the FSH infusion was evaluated in six animals which were treated with a specific antiserum against bovine LH (LH-AS) 15–20 h before the start of FSH treatment. In the absence of LH-AS, infusion of FSH alone or with large or small pulses of LH stimulated the development of a normal number of small follicles (≤ 2·5 mm in diameter) and large follicles (> 2·5 mm in diameter). These follicles had normal diameter and steroid secretion compared with control ewes on day 8 of the luteal phase. In contrast, the animals pretreated with LH-AS developed no follicles > 2·0 mm in diameter but the number of small follicles per ewe was significantly (P < 0·05) increased. These results support the hypothesis that FSH in the absence of pulsatile LH release stimulates preovulatory follicular development in ewes treated with GnRH agonist. The follicular response to LH pulses of different amplitude is dependent on both the stage of development of the follicle and the peripheral concentration of FSH. The endogenous basal level of LH present throughout the FSH infusion is essential for FSH to induce follicle growth beyond > 2·5 mm in diameter. Journal of Endocrinology (1991) 128, 449–456

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

The antagonistic effect of exogenous LH pulses on FSH-stimulated preovulatory follicle growth in ewes chronically treated with a gonadotrophin-releasing hormone agonist

1990 ◽  
Vol 127 (2) ◽  
pp. 273-283 ◽  
Author(s):  
H. M. Picton ◽  
C. G. Tsonis ◽  
A. S. McNeilly
Keyword(s):  
Luteal Phase ◽  
Follicular Development ◽  
High Amplitude ◽  
Follicle Growth ◽  
High Concentration ◽  
Continuous Administration ◽  
Releasing Hormone ◽  
Low Concentrations ◽  
Gonadotrophin Releasing Hormone ◽  
The Mean

ABSTRACT The hypogonadotrophism model induced by the chronic administration of gonadotrophin-releasing hormone (GnRH) agonist was used to investigate the effects of different concentrations of FSH with or without LH pulses on the stimulation of follicular development in the ewe. Continuous administration of an agonist (buserelin) by osmotic minipump to thirty-six Welsh Mountain ewes from the early luteal phase for 5 weeks resulted in a sustained suppression of the plasma concentration of FSH and inhibited the pulsatile release of LH. The inhibition of gonadotrophin secretion was due to the desensitization and/or down-regulation of pituitary gonadotroph function, since the agonist-treated animals showed no response to a challenge of 1 μg GnRH. During week 6 of agonist treatment, ewes were infused with either 4-hourly pulses of ovine LH (9 μg/pulse), low concentrations of ovine FSH (3 μg/h) or high concentrations of FSH (9 μg/h) alone or with 4-hourly pulses of LH. After 5 days of gonadotrophin infusion, there was no difference between the mean number of follicles per ewe from the animals treated with LH alone, low concentrations of FSH with or without LH pulses or the high concentration of FSH alone compared with the mean number of follicles from control ewes on day 8 of the luteal phase. Infusion of the high concentration of FSH alone stimulated the development of an increased number of large oestrogenic follicles (follicles > 2·5 mm in diameter and secreting > 3·7 nmol oestradiol/h in vitro) compared with control ewes. The addition of high-amplitude LH pulses to the infusion of the high concentration of FSH prevented follicles developing beyond 2·5 mm in diameter, but doubled the number of small follicles (≤2·5 mm) present in the ovaries. These results show that normal follicular development can be induced by physiological concentrations of FSH alone in the absence of pulsatile LH release. The addition of high-amplitude LH pulses antagonized this stimulatory effect of FSH on follicle growth in the ewe. Journal of Endocrinology (1990) 127, 273–283

Effect of long-term inhibition of gonadotrophin secretion by the gonadotrophin-releasing hormone agonist, buserelin, on sex steroid secretion and ovarian morphology in polycystic ovary syndrome

1990 ◽  
Vol 125 (2) ◽  
pp. 317-325 ◽  
Author(s):  
A. F. Macleod ◽  
M. J. Wheeler ◽  
P. Gordon ◽  
C. Lowy ◽  
P. H. Sönksen ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Gnrh Agonist ◽  
Polycystic Ovary ◽  
Normal Subjects ◽  
Sex Hormone Binding Globulin ◽  
Plasma Testosterone ◽  
Ovary Syndrome ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone

ABSTRACT In order to investigate the effect of long-term suppression of the gonadotrophin axis in polycystic ovary syndrome, eight affected subjects were given s.c. infusions of gonadotrophin-releasing hormone (GnRH) agonist buserelin for 12 weeks. Hormone measurement and ultrasound studies were carried out weekly, from 6 weeks before to 12 weeks after administration of buserelin. An overnight dexamethasone-suppression test was carried out before and after treatment. Maximal suppression of LH to below the lower limit of that in normal subjects occurred after 6 weeks of treatment with buserelin. Plasma testosterone and androstenedione fell to normal levels during the infusion but reached pretreatment levels during the follow-up period. There was no effect of buserelin on plasma dehydroepiandrosterone sulphate or sex hormone-binding globulin. Ovarian size decreased significantly during the infusion with the disappearance of cysts in six subjects. After cessation of buserelin therapy, there was rapid and spontaneous ovulation which occurred within 3 weeks in all subjects. The results suggest that treatment with this GnRH agonist facilitates ovulation in this condition. Journal of Endocrinology (1990) 125, 317–325

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