The effect of a potent gonadotrophin-releasing hormone antagonist on ovarian secretion of oestradiol, inhibin and androstenedione and the concentration of LH and FSH during the follicular phase of the sheep oestrous cycle

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.


1984 ◽  
Vol 101 (3) ◽  
pp. 365-370 ◽  
Author(s):  
B. J. McLeod ◽  
W. Haresign

ABSTRACT Oestrus was synchronized in 15 naturally cyclic ewes by the administration of a prostaglandin F2α analogue. Groups of five ewes were then treated i.v. with either small doses of gonadotrophin releasing hormone (GnRH; 125 or 250 ng/injection) or saline, at 2-h intervals from day 14 of the subsequent cycle until 24 h after the onset of oestrus. Treatment with GnRH induced episodic LH release which continued until the onset of a preovulatory LH surge. Mean plasma LH concentrations over this period were significantly (P< 0·001) higher in animals receiving 250 ng GnRH (2·44±0·11 μg/l) than in those receiving either 125 ng GnRH (1·17±0·06 μg/l) or saline (1·14±0·05 μg/l). However, GnRH treatment did not influence the timing of oestrus or mean ovulation rates. J. Endocr. (1984) 101, 365–370


1990 ◽  
Vol 126 (3) ◽  
pp. 385-393 ◽  
Author(s):  
B. K. Campbell ◽  
G. E. Mann ◽  
A. S. McNeilly ◽  
D. T. Baird

ABSTRACT The pattern of pulsatile secretion of inhibin, oestradiol and androstenedione by the ovary at different stages of the oestrous cycle in sheep was studied in five Finn–Merino ewes in which the left ovary had been autotransplanted to the neck. The ewes had jugular venous blood samples collected at 4-hourly intervals from 42 h before the induction of luteolysis by i.m. injection of cloprostenol (100 μg) on day 10 of the oestrous cycle, until day 3 of the following cycle. There were five periods of intensive blood sampling, when both ovarian and jugular venous blood samples were collected, as follows: (a) mid-luteal phase, before the second injection of cloprostenol on day 10 (15-min intervals for 6 h); (b) early follicular phase, 24 h after the second injection of cloprostenol (10-min intervals for 4 h); (c) late follicular phase, 48 h after the second injection of cloprostenol (10-min intervals for 4 h); (d) after the LH surge on day 1 of the cycle, 76 h after the second injection of cloprostenol (10-min intervals for 4 h); (e) early luteal phase on day 3 of the cycle, 120 h after the second injection of cloprostenol (10-min intervals for 3 h). Plasma was collected and the samples assayed for LH, FSH, progesterone, oestradiol, androstenedione and inhibin. The ovarian secretion rates for oestradiol, androstenedione and inhibin were calculated. All ewes responded normally to the luteolytic dose of cloprostenol with the preovulatory surge of LH occurring within 56·4±1·6 h (mean ± s.e.m.) followed by the establishment of a normal luteal phase. The pulse frequency of LH, oestradiol and androstenedione increased in the transition from the luteal to the follicular phase (P<0·01). On day 1 of the cycle LH secretion consisted of low-amplitude high-frequency pulses (1·0±0·1 pulse/h) to which androstenedione, but not oestradiol, responded. On day 3 of the cycle LH secretion was similar to that on day 1 but both androstenedione and oestradiol secretion were pulsatile in response to LH, indicating the presence of oestrogenic follicles. The stage of the cycle had no significant effects on LH pulse amplitude and nadir but the ovarian secretory response to LH stimulation did vary with the stage of the cycle. Prolactin pulse frequency, amplitude and nadir were higher (P<0·05) during the follicular phase than the luteal phase. Prolactin pulse frequency was depressed (P<0·05) on day 1 of the cycle but increased to follicular phase levels on day 3. Prolactin pulse frequency was significantly correlated to oestradiol pulse frequency (r = 0·54; P<0·01). During the luteal phase there were insufficient oestradiol pulses to obtain an estimate of pulse amplitude and nadir but both these parameters reached their highest level during the late follicular phase, fell to negligible levels on day 1 and increased to early follicular phase levels on day 3. Androstenedione pulse amplitude and nadir exhibited similar but less marked variation. Inhibin secretion was episodic at all stages of the cycle examined but did not exhibit significant variation with stage of cycle in any of the parameters of episodic secretion measured. Inhibin pulses were not related to either LH or prolactin at any stage of the cycle. FSH secretion was not detectably pulsatile but jugular venous concentrations of FSH at each stage of the oestrous cycle were negatively correlated with mean oestradiol (r= −0·52; P<0·01 but not inhibin secretion (r = 0·19). We conclude that (i) LH secretion is pulsatile at all stages of the oestrous cycle but the steroidogenic responses of the ovary varies with the stage of the cycle, reflecting changes in characteristics of the follicle population, (ii) ovarian inhibin secretion is episodic and displays little change with the stage of the oestrous cycle and (iii) episodic inhibin secretion is not related to either pulses of LH or prolactin. The aetiology of these inhibin pulses therefore remains unknown. Journal of Endocrinology (1990) 126, 385–393


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 127 (1) ◽  
pp. 23-32 ◽  
Author(s):  
D. T. Baird ◽  
B. K. Campbell ◽  
A. S. McNeilly

ABSTRACT An experiment was conducted to examine the effect of steroid-free ovine follicular fluid (oFF) on ovarian hormone secretion. Eight Merino × Finnish Landrace ewes in which the left ovary and vascular pedicle had been autotransplanted to a site in the neck were studied during the breeding season. Luteal regression was induced in all animals by injection of cloprostenol (100 μg, i.m.) on day 10 of the luteal phase. Four of the eight animals were treated with steroid-free oFF (3 ml, s.c.) in the early follicular phase, 24 and 36 h after injection of cloprostenol. Samples of both ovarian and jugular venous blood were collected at 4-h intervals from 20 h before until 96 h after injection of cloprostenol. Ovarian and jugular venous blood samples were also collected at 10-min intervals from 48 to 52 h after injection of cloprostenol to investigate the pattern of pulsatile secretion of ovarian hormones. Samples were assayed for oestradiol, androstenedione, testosterone and inhibin and the ovarian secretion rates calculated. Both injections of oFF resulted in a fourfold increase in the concentration of inhibin in jugular venous plasma within 4–8 h of administration (P < 0·01) with concentrations remaining increased (P < 0·05) until 56 h after cloprostenol (32 h after the first oFF injection). Following oFF injection there was a profound (100%; P < 0·001) and prolonged decrease in the peripheral concentration of FSH until 60 h after cloprostenol at which time the concentration of FSH increased five- to sixfold (P < 0·001) to a peak lasting 24 h. In contrast to FSH, the concentration of LH in jugular venous plasma rose immediately following oFF treatment and continued to increase, exhibiting a profile similar to that described for FSH. No preovulatory LH surge was detected in any of the oFF-treated ewes while untreated ewes had an LH surge within 58·0±1·2 (s.e.m.) h. Within 8 h of the first injection of oFF the ovarian secretion rate of oestradiol, androstenedione and inhibin began to decline to reach a nadir of less than 1 ng/min within 32–36 h (56–60 h after cloprostenol; P < 0·01). Testosterone secretion, already barely detectable, did not change significantly following injection of oFF but remained low for 36 h following oFF and did not exhibit the increase observed over this period in controls. After injection of oFF the episodic secretion of oestradiol, androstenedione, testosterone and inhibin was markedly suppressed in spite of numerous pulses of LH. Re-establishment of inhibin, androstenedione and testosterone secretion began from around 36 h after injection of oFF and continued to increase for the remainder of the experimental period (P < 0·001). The re-establishment of oestradiol secretion, however, took until 60 h after oFF treatment (84 h after cloprostenol). This increase in ovarian hormone secretion was temporally related to the decrease in the concentration of FSH and LH in jugular venous plasma that was observed at the end of the experimental period. We conclude that treatment of ewes with steroid-free oFF during the follicular phase of the oestrous cycle results in the immediate inhibition of the ovarian secretion of oestradiol, inhibin, androstenedione and testosterone. This effect can most probably be attributed to the depression in FSH that occurs following oFF injection, although the possibility exists that other factors present in oFF are acting directly on the ovary to inhibit follicular growth. Journal of Endocrinology (1990) 127, 23–32


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


1987 ◽  
Vol 113 (2) ◽  
pp. 183-192 ◽  
Author(s):  
C. H. G. Irvine ◽  
S. L. Alexander

ABSTRACT We have described a novel technique for collecting pituitary venous effluent in the horse by placing a cannula in the intercavernous sinus close to the outlet of the pituitary veins using a venous pathway unique to equids. Cannula placement and blood collection are carried out painlessly in fully conscious, ambulatory, unstressed animals. There is no interference to hypothalamic, pituitary or target organ function. The blood collected contains readily measurable concentrations of gonadotrophin-releasing hormone, and LH concentrations which can be up to 40 times those in concurrent peripheral blood samples. Four millilitre blood samples, a quantity which permits simultaneous measurement of many hypothalamic and pituitary hormones, can be collected at 2-min intervals for several days. Intercavernous sinus blood flow can be calculated allowing secretion rates of hypothalamic and pituitary hormones to be determined for any time-period. This model is uniquely useful for investigating the normal functional characteristics of several neuroendocrine and endocrine systems. J. Endocr. (1987) 113, 183–192


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

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