Effect of a gonadotrophin-releasing hormone antagonist on luteinising hormone secretion and early pregnancy in gilts

2003 ◽  
Vol 15 (8) ◽  
pp. 451 ◽  
Author(s):  
J. V. Virolainen ◽  
R. J. Love ◽  
A. Tast ◽  
O. A. T. Peltoniemi

The aims of the present study were: (1) to determine the duration of suppression of luteinising hormone (LH) following a single treatment with a gonadotrophin-releasing hormone (GnRH) antagonist (BIM-21009; Biomeasure) at a dose of 100 μg kg−1; (2) to block LH pulses only for certain days of pregnancy; and (3) to determine the period of early pregnancy most susceptible to suppression of LH. Three groups of gilts were injected with 100 μg kg−1 on Day 16 (n = 5), 14 (n = 6) or 19 (n = 4) of pregnancy. Blood for LH analysis was collected at 20-min intervals for 12 h on the day before treatment and during varying stages of early pregnancy. Blood for progesterone analysis was collected daily and development of pregnancy was followed using real-time ultrasound. Prior to treatment, gilts had 2.6 ± 0.7 LH pulses per 12 h. The GnRH antagonist abolished LH pulses for a period of 2.7 ± 1.8 days and, thereafter, suppressed the resumed LH pulses (P < 0.05). Pregnancy was disrupted in three pigs (20%) with a mean treatment-to-abortion period of 4.7 days concurrent with a mean treatment-to-progesterone decline interval of 4.3 days. In a proportion of pigs, short-term LH suppression may cause early disruption of pregnancy.

1990 ◽  
Vol 126 (3) ◽  
pp. 377-384 ◽  
Author(s):  
B. K. Campbell ◽  
A. S. McNeilly ◽  
H. M. Picton ◽  
D. T. Baird

ABSTRACT By selective removal and replacement of LH stimulation we sought to examine the relative importance of inhibin and oestradiol in controlling FSH secretion, and the role of LH in the control of ovarian hormone secretion, during the follicular phase of the oestrous cycle. Eight Finn–Merino ewes which had one ovary removed and the other autotransplanted to a site in the neck were given two injections of a gonadotrophin-releasing hormone (GnRH) antagonist (50 μg/kg s.c.) in the follicular phase of the cycle 27 h and 51 h after luteal regression had been induced by cloprostenol (100 μg i.m.). Four of the ewes received, in addition, i.v. injections of 2·5 μg LH at hourly intervals for 23 h from 42 to 65 h after GnRH antagonist treatment. Ovarian jugular venous blood samples were taken at 10-min intervals for 3 h before and 5 h after the injection of antagonist (24–32 h after cloprostenol) and from 49 to 53 h after antagonist (74–78 h after cloprostenol). Additional blood samples were taken at 4-h intervals between the periods of intensive blood sampling. The GnRH antagonist completely inhibited endogenous pulsatile LH secretion within 1 h of injection. This resulted in a marked decrease in the ovarian secretion of oestradiol and androstenedione (P<0·001), an effect that was reversible by injection of exogenous pulses of LH (P<0·001). The pattern of ovarian inhibin secretion was episodic, but removal or replacement of stimulation by LH had no effect on the pattern or level of inhibin secretion. Peripheral concentrations of FSH rose (P<0·01) within 20 h of administration of the antagonist and these increased levels were maintained in ewes given no exogenous LH. In ewes given LH, however, FSH levels declined within 4 h of the first LH injection and by the end of the experimental period the levels of FSH were similar to those before administration of antagonist (P<0·01). These results confirm that ovarian oestradiol and androstenedione secretion, but not inhibin secretion, is under the acute control of LH. We conclude that oestradiol, and not inhibin, is the major component of the inhibitory feedback loop controlling the pattern of FSH secretion during the follicular phase of the oestrous cycle in ewes. Journal of Endocrinology (1990) 126, 377–384


2005 ◽  
Vol 17 (7) ◽  
pp. 721 ◽  
Author(s):  
C. Tasende ◽  
M. Rodríguez-Piñón ◽  
S. Acuña ◽  
E. G. Garófalo ◽  
M. Forsberg

The present study investigated the pituitary oestrogen (ER) and progesterone (PR) receptor concentrations in ewes during the oestrous cycle in the breeding season (n = 19), and in anoestrous ewes treated with gonadotrophin-releasing hormone (GnRH) (n = 11) and anoestrous ewes treated with progesterone + GnRH (n = 11). The pituitary ER and PR concentrations at the expected time of ovulation and in the early and late luteal phases were measured by binding assay. The pattern of pituitary ER and PR concentrations in the progesterone + GnRH-treated ewes resembled the pattern found during the normal oestrous cycle, with ER and PR concentrations decreasing from the time of ovulation to the early luteal phase. In contrast, in ewes treated with GnRH alone, ER and PR concentrations increased in the early luteal phase, which may increase the inhibitory effects of steroid hormones on luteinising hormone secretion, ultimately leading to the development of subnormal luteal phases.


1989 ◽  
Vol 123 (1) ◽  
pp. 83-91 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi

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


2009 ◽  
Vol 21 (4) ◽  
pp. 339-345 ◽  
Author(s):  
P. E. Chappell ◽  
C. P. Goodall ◽  
K. J. Tonsfeldt ◽  
R. S. White ◽  
E. Bredeweg ◽  
...  

1986 ◽  
Vol 109 (2) ◽  
pp. 155-161 ◽  
Author(s):  
J. E. A. McIntosh ◽  
R. P. McIntosh

ABSTRACT Our aim was to determine whether release of LH and FSH can be controlled differentially by the characteristics of applied signals of stimulatory gonadotrophin-releasing hormone (GnRH) alone, free of the effects of steroid feedback or other influences from the whole animal. The outputs of both gonadotrophins were significantly correlated (r≈0·90; P<0·0005) when samples of freshly dispersed sheep pituitary cells were perifused in columns for 7 h with medium containing a range of concentrations of GnRH in various patterns of pulses. Hormone released in response to the second, third and fourth pulses from every column was analysed in detail. Dose–response relationships for both LH and FSH were very similar when cells were stimulated with 5–8500 pmol GnRH/1 in 5-min pulses every hour. When GnRH was delivered in pulses at a maximally stimulating level, the outputs of both hormones increased similarly with increasing inter-pulse intervals. Efficiency of stimulation (release of gonadotrophin/unit stimulatory GnRH) decreased (was desensitized) with increasing pulse duration in the same way for both hormones. Thus, varying the dose, interval and duration of GnRH pulses did not alter the proportions of LH and FSH released in the short-term from freshly dissociated cells. However, the same cell preparations released more LH relative to FSH when treated with maximally stimulating levels of GnRH for 3 h in the presence of 10% serum from a sheep in the follicular phase of its ovulatory cycle compared with charcoal-treated serum. Because there was no gonadotrophin synthesis under the conditions used in vitro these results suggest that changes in the LH/FSH ratio seen in whole animals are more likely to result from differential clearance from the circulation, ovarian feedback at the pituitary, differential synthesis in intact tissue or another hormone influencing FSH secretion, rather than from differences in the mechanism of acute release controlled by GnRH. J. Endocr. (1986) 109, 155–161


1995 ◽  
Vol 132 (3) ◽  
pp. 357-362 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
E Aguilar

Tena-Sempere M, Pinilla L, Aguilar E. Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone agonist-treated male rats. Eur J Endocrinol 1995;132: 357–62. ISSN 0804–4643 The pituitary component of the feedback mechanisms exerted by testicular factors on gonadotropin secretion was analyzed in adult male rats treated with a potent gonadotropin-releasing hormone (GnRH) antagonist. In order to discriminate between androgens and testicular peptides, groups of males were orchidectomized (to eliminate androgens and non-androgenic testicular factors) or injected with ethylene dimethane sulfonate (EDS), a selective toxin for Leydig cells (to eliminate selectively androgens) and treated for 15 days with vehicle or the GnRH antagonist Ac-d-pClPhe-d-pClPhe-d-TrpSer-Tyr-d-Arg-Leu-Arg-Pro-d-Ala-NH2CH3COOH (Org.30276, 5 mg/kg/72 hours). Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured 7 and 14 days after the beginning of treatment. We found that: in males treated with GnRH antagonist, orchidectomy or EDS treatment did not induce any increase in LH secretion; and orchidectomy, but not EDS treatment, increased FSH secretion in GnRH-treated males. The present results show that negative feedback of testicular factors on LH secretion is mediated completely through changes in GnRH actions. In contrast, a part of the inhibitory action of the testis on FSH secretion is exerted directly at the pituitary level. It can be hypothesized that non-Leydig cell testicular factor(s) inputs at different levels of the hypothalamic–pituitary axis in controlling LH and FSH secretion. Manuel Tena-Sempere, Department of Physiology, Faculty of Medicine, University of Córdoba, 14004 Córdoba, Spain


1976 ◽  
Vol 81 (3) ◽  
pp. 680-684 ◽  
Author(s):  
Richard A. Donald ◽  
Eric A. Espiner ◽  
R. John Cowles ◽  
Joy E. Fazackerley

ABSTRACT Cyproterone acetate (100–150 mg daily) was administered to 8 male patients with excessive libido. Within 3 months a significant fall (P < 0.02) in plasma testosterone was demonstrated. The plasma luteinising hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotrophin releasing hormone (LH/FSH-RH) were also significantly impaired (P < 0.05). A direct correlation between the resting plasma testosterone level and the LH response to LH/FSH-RH was demonstrated (r = 0.743). It is concluded that the fall in plasma testosterone levels in patients receiving cyproterone acetate may be attributed to suppression of LH release, rather than an antiandrogen effect on the testis or hypothalamus.


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