Effect of graded doses of gonadotrophin-releasing hormone on serum LH concentrations in mares in various reproductive states: comparison with endogenously generated LH pulses

1986 ◽  
Vol 110 (1) ◽  
pp. 19-26 ◽  
Author(s):  
S. L. Alexander ◽  
C. H. G. Irvine
Keyword(s):  
Luteal Phase ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Hormone Release ◽  
Response Curves ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Small Doses ◽  
Gonadotrophin Releasing Hormone ◽  
Log Linear

ABSTRACT Luteinizing hormone release induced by a range of small (3·3–33 μg) and large (300–500 μg) i.v. doses of gonadotrophin-releasing hormone (GnRH) was measured in acyclic (n = 4), luteal phase (n = 3) and follicular phase (n = 5) mares and compared with endogenously generated LH pulses in the same reproductive states. Extrapolation from log–linear dose–response curves showed that an LH pulse comparable to an endogenous one would be simulated by i.v. injection of 7·0 (n = 4) and 4·1 (n = 6) μg GnRH in luteal and follicular phase mares respectively; a much smaller dose than the 500 μg usually given clinically or experimentally. In acyclic mares (n = 4), LH pulses occurred too infrequently to be characterized. At small doses of GnRH the amount of LH released by the same dose was similar in all three reproductive states, although the steroid hormone milieu differed markedly. This implies that observed differences between states in mean (± s.e.m.) serum LH concentrations (0·7 ± 0·01, 1·2 ± 0·03 and 11·6 ± 0·33 (μg/l) in acyclic, luteal and follicular phase mares respectively) were produced by differences in GnRH pulse frequency and/or amplitude and not by steroid-mediated changes in pituitary response to GnRH. In acyclic, luteal and follicular phase mares, LH pulse frequency was: immeasurably low, 0·09 and 1·14 pulses/h respectively, which supports the important contribution of pulse frequency to determining mean LH concentration. The LH response to large doses of GnRH was significantly greater in the luteal than in the follicular phase, and was greater than the response to 33 μg in the luteal phase but not in the other two states. Thus, to a large but not to a small dose of GnRH, the pituitary appeared most responsive in the luteal phase. Therefore, in studies of the physiology of the hypothalamic-pituitary system, small doses of GnRH, which induce physiologically sized LH responses, may be preferred to large doses, which result in a level of stimulation to which the pituitary is never naturally exposed and to which it may respond in a non-physiological manner. J. Endocr. (1986) 110, 19–26

Effect of the body condition of ewes on the secretion of LH and FSH and the pituitary response to gonadotrophin-releasing hormone

1989 ◽  
Vol 120 (3) ◽  
pp. 497-502 ◽  
Author(s):  
S. M. Rhind ◽  
S. McMillen ◽  
W. A. C. McKelvey ◽  
F. F. Rodriguez-Herrejon ◽  
A. S. McNeilly
Keyword(s):  
Body Condition ◽  
Luteal Phase ◽  
Body Condition Score ◽  
Pulse Amplitude ◽  
Ovarian Hormones ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
High Body ◽  
Condition Score ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The effects of body fat content (body condition) of ewes on hypothalamic activity and gonadotrophin-releasing hormone (GnRH) secretion and on pituitary sensitivity to GnRH were investigated using Scottish Blackface ewes. Two groups of 12 ewes were fed so that they achieved either a high body condition score (2·98, s.e.m. = 0·046; approximately 27% of empty body weight as fat) or a low body condition score (1·94, s.e.m. = 0·031; approximately 19% of empty body weight as fat) by 4 weeks before the period of study. Thereafter, they were differentially fed so that the difference in mean condition score was maintained. Oestrus was synchronized, and on day 11 of the subsequent cycle half of the ewes of each group were ovariectomized. On day 12, the remaining ewes were injected (i.m.) with 100 μg prostaglandin F2α analogue and ovariectomized 30 h later. Numbers of large ovarian follicles and corpora lutea present at ovariectomy were recorded. Blood samples were collected at 15-min intervals for 12 h on day 10 of the cycle (luteal phase) and at 10-min intervals from 24 to 30 h after prostaglandin injection (follicular phase). At days 2 and 7 after ovariectomy, samples were collected at 15-min intervals for 8 h and ewes were then injected with 10 μg GnRH and samples were collected for a further 3 h. Samples were assayed for LH and FSH. Ewes in high body condition had more more large follicles than ewes in low body condition during the luteal phase (15·3 vs 6·5; P < 0·05) and follicular phase (11·5 vs 7·0; NS) and a slightly higher mean ovulation rate (1·50 vs 1·20; NS). However, during the luteal and follicular phases of the cycle before ovariectomy there was no effect of condition score on mean LH or FSH concentrations or mean LH pulse frequency or pulse amplitude. Two days after ovariectomy, ewes of high body condition had a higher mean LH pulse frequency than ewes of low body condition (P < 0·05) and higher mean FSH concentrations (P < 0·05). Mean LH concentration and pulse amplitude were not affected. LH and FSH profiles were not affected by body condition on day 7. GnRH-induced increases in LH and FSH concentrations on days 2 and 7 were not affected by body condition. At day 7, but not day 2, ewes ovariectomized during the luteal phase of the cycle had a significantly (P < 0·05) greater GnRH-induced LH release compared with ewes ovariectomized during the follicular phase. It is concluded that body condition directly affects hypothalamic activity and GnRH secretion, but not pituitary sensitivity to GnRH, and that effects on reproductive performance are also mediated through changes in ovarian hormones or in hypothalamo-pituitary sensitivity to ovarian hormones. Journal of Endocrinology (1989) 120, 497–502

Effect of pulsatile infusion of gonadotrophin-releasing hormone on plasma oestradiol-17β concentrations and follicular development during naturally and artificially maintained high levels of plasma progesterone in heifers

1987 ◽  
Vol 112 (1) ◽  
pp. 77-85 ◽  
Author(s):  
R. G. Glencross
Keyword(s):  
Luteal Phase ◽  
Indirect Evidence ◽  
Follicular Development ◽  
Pulse Frequency ◽  
Oestrous Cycle ◽  
Plasma Progesterone ◽  
Releasing Hormone ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Plasma Oestradiol

ABSTRACT To stimulate a follicular-phase pattern of pulsatile LH release, gonadotrophin-releasing hormone (GnRH; 5 μg) was infused (i.v.) hourly into heifers for periods of 5–11 days during the luteal phase of the oestrous cycle, and also when plasma progesterone levels were increased artificially by means of a progesterone-releasing intravaginal device. Plasma oestradiol-17β concentrations increased from basal (EEE 2·5 pmol/l) to preovulatory peak levels (20–30 pmol/l) during the first 3 days of GnRH treatment. They were maintained at these values before returning to basal levels within 24 h of cessation of infusion. This response occurred regardless of the source of progesterone (endogenous or administered). Follicular development was observed by ovarian palpation (per rectum) in some heifers at the time of maximum secretion of oestradiol-17β. There was no detectable cervical mucus secretion or oestrous behaviour during these periods of high oestradiol-17β levels and ovulation did not occur. Treatment with GnRH did not affect plasma progesterone concentrations or oestrous cycle length. The study shows that oestradiol-17β secretion and follicular development (and the accompanying oestrus and ovulation) are suppressed during the luteal phase of the cycle by high concentrations of plasma progesterone, and provides strong indirect evidence that such inhibition is associated with a reduction in the pulse frequency of LH release. J. Endocr. (1987) 112, 77–85

Effect of level of food intake of ewes on the secretion of LH and FSH and on the pituitary response to gonadotrophin-releasing hormone in ovariectomized ewes

1989 ◽  
Vol 121 (2) ◽  
pp. 325-330 ◽  
Author(s):  
S. M. Rhind ◽  
G. B. Martin ◽  
S. McMillen ◽  
C. G. Tsonis ◽  
A. S. McNeilly
Keyword(s):  
Food Intake ◽  
Luteal Phase ◽  
Bolus Injection ◽  
Daily Intake ◽  
Follicular Phase ◽  
Plasma Prolactin ◽  
High Intake ◽  
Releasing Hormone ◽  
Pituitary Glands ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The effect of level of food intake on LH and FSH profiles and pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) was investigated in two groups of 12 ovariectomized ewes. Ewes with a high intake (group H) had a mean daily intake (± s.e.m.) of 1·99 ± 0·075 kg dry matter (DM)/head per day while ewes with a moderate intake (group M) consumed a mean of 1·02 ± 0·021 kg DM/head per day. Ovaries were surgically removed from six ewes of each group on day 11 of the luteal phase and from the remainder 30 h after an injection of 100 μg prostaglandin analogue given on day 11 to induce luteolysis. During both the luteal phase and the follicular phase, mean LH and FSH concentrations and LH pulse frequencies and amplitudes were unaffected by the level of intake but mean plasma prolactin concentrations were higher (P < 0·05) in group H than in group M ewes in the follicular phase. Mean LH and FSH concentrations at day 2 after ovariectomy were unaffected by treatment while mean prolactin concentrations were higher (P < 0·05) in group H than in group M ewes. At day 7 after ovariectomy, mean LH and FSH concentrations were lower (P < 0·05) in group H than in group M ewes although mean LH pulse frequencies and pulse amplitudes were not significantly affected by the level of intake at either time. The level of food intake and the stage of the oestrous cycle at the time of ovariectomy did not affect the amount of LH released in response to a bolus injection of GnRH (10 μg, i.v.) but the FSH response was significantly (P < 0·05) greater in group M than in group H ewes. It is concluded that the pituitary glands of ovariectomized ewes with moderate levels of intake are more responsive to GnRH than those of ewes with a high intake and that hypothalamic activity and GnRH secretion are not affected by the level of food intake. Journal of Endocrinology (1989) 121, 325–330

Plasma LH concentrations in the ewe in response to repeated injections of low doses of gonadotrophin releasing hormone during the follicular phase of the oestrous cycle

1984 ◽  
Vol 101 (3) ◽  
pp. 365-370 ◽  
Author(s):  
B. J. McLeod ◽  
W. Haresign
Keyword(s):  
Follicular Phase ◽  
Oestrous Cycle ◽  
Low Doses ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Subsequent Cycle ◽  
Small Doses ◽  
Prostaglandin F ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

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

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

Seasonal and steroid-dependent effects on the modulation of LH secretion in the ewe by intracerebroventricularly administered β-endorphin or naloxone

1989 ◽  
Vol 122 (2) ◽  
pp. 509-517 ◽  
Author(s):  
R. J. E. Horton ◽  
H. Francis ◽  
I. J. Clarke
Keyword(s):  
Breeding Season ◽  
Luteal Phase ◽  
Pulse Frequency ◽  
Opioid Peptide ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Opioid Antagonist ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Lh Secretion

ABSTRACT The natural opioid ligand, β-endorphin, and the opioid antagonist, naloxone, were administered intracerebroventricularly (i.c.v.) to evaluate effects on LH secretion in ovariectomized ewes and in ovariectomized ewes treated with oestradiol-17β plus progesterone either during the breeding season or the anoestrous season. Ovary-intact ewes were also studied during the follicular phase of the oestrous cycle. Jugular blood samples were taken at 10-min intervals for 8 h and either saline (20–50 μl), 100 μg naloxone or 10 μg β-endorphin were injected i.c.v. after 4 h. In addition, luteal phase ewes were injected i.c.v. with 25 μg β-endorphin(1–27), a purported endogenous opioid antagonist. In ovariectomized ewes, irrespective of season, saline and naloxone did not affect LH secretion, but β-endorphin decreased the plasma LH concentrations, by reducing LH pulse frequency. The effect of β-endorphin was blocked by administering naloxone 30 min beforehand. Treating ovariectomized ewes with oestradiol-17β plus progesterone during the breeding season reduced plasma LH concentrations from 6–8 μg/l to less than 1 μg/l. In these ewes, saline did not alter LH secretion, but naloxone increased LH pulse frequency and the plasma concentrations of LH within 15–20 min. During anoestrus, the combination of oestradiol-17β plus progesterone to ovariectomized ewes reduced the plasma LH concentrations from 3–5 μg/l to undetectable levels, and neither saline nor naloxone affected LH secretion. During the follicular phase of the oestrous cycle, naloxone enhanced LH pulse frequency, which resulted in increased plasma LH concentrations; saline had no effect. In these sheep, β-endorphin decreased LH pulse frequency and the mean concentrations of LH, and this effect was prevented by the previous administration of naloxone. The i.c.v. administration of β-endorphin(1–27) to luteal phase ewes did not affect LH secretion. These data demonstrate the ability of a naturally occurring opioid peptide to inhibit LH secretion in ewes during the breeding and non-breeding seasons, irrespective of the gonadal steroid background. In contrast, whilst the gonadal steroids suppress LH secretion in ovariectomized ewes during both seasons, they only appear to activate endogenous opioid peptide (EOP)-mediated inhibition of LH secretion during the breeding season. Furthermore, these data support the notion that LH secretion in ovariectomized ewes is not normally under the control of EOP, so that naloxone has no effect. Journal of Endocrinology (1989) 122, 509–517

Varying the patterns and concentrations of gonadotrophin-releasing hormone stimulation does not alter the ratio of LH and FSH released from perifused sheep pituitary cells

1986 ◽  
Vol 109 (2) ◽  
pp. 155-161 ◽  
Author(s):  
J. E. A. McIntosh ◽  
R. P. McIntosh
Keyword(s):  
Dose Response ◽  
Dose Interval ◽  
Follicular Phase ◽  
Pituitary Cells ◽  
Ovulatory Cycle ◽  
Short Term ◽  
Releasing Hormone ◽  
Dissociated Cells ◽  
Gonadotrophin Releasing Hormone

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

HYPOTHALAMIC, PITUITARY AND TESTICULAR FUNCTION DURING SEXUAL MATURATION OF THE MALE RAT

1977 ◽  
Vol 72 (1) ◽  
pp. 17-26 ◽  
Author(s):  
A. H. PAYNE ◽  
R. P. KELCH ◽  
E. P. MURONO ◽  
J. T. KERLAN
Keyword(s):  
Dehydrogenase Activity ◽  
Sexual Maturation ◽  
Hydroxysteroid Dehydrogenase ◽  
Male Rat ◽  
Releasing Hormone ◽  
Isomerase Activity ◽  
Serum Lh ◽  
Rate Of Increase ◽  
Gonadotrophin Releasing Hormone

SUMMARY Hypothalamic content of gonadotrophin-releasing hormone (GnRH), serum LH and FSH, capacity of the testis to synthesize testosterone in vitro, and testicular 5-ene-3β-hydroxysteroid dehydrogenase-isomerase and 17β-hydroxysteroid dehydrogenase were measured in groups of rats at approximately 5 day intervals from birth to day 64 and at days 74 and 89. The capacity of the testes to synthesize testosterone in vitro was measured in the presence of a saturating dose of rat LH. Gonadotrophin-releasing hormone increased steadily from 0·17 ng per hypothalamus at birth to a maximum of 7 ng at day 52 and then remained constant. LH concentrations were highly variable and often exceeded adult values between days 10 and 32. After day 32 a steady rise was observed which reached adult values between days 37 and 42. FSH concentrations markedly increased from 255 ng/ml observed at birth and day 10 to a peak value of 1000 ng/ml at day 32. Subsequently there was a steady decline in FSH values until day 74 when the concentration returned to values found at birth. 5-ene-3β-Hydroxysteroid dehydrogenase-isomerase activity exhibited a rapid increase between days 12 and 19 followed by an even greater rate of increase between days 19 and 32 when adult levels were attained. 17β-Hydroxysteroid dehydrogenase activity was very low between birth and day 22. Enzyme activity began to increase at day 22 with a rapid increase in activity observed between days 37 and 58. The increase in capacity to synthesize testosterone closely followed the increase in 17β-hydroxysteroid dehydrogenase activity. The study demonstrates that during sexual maturation in the male rat, changes in serum LH and FSH do not reflect changes in hypothalamic GnRH. The appearance of Leydig cells as monitored by 5-ene-3β-hydroxysteroid dehydrogenase-isomerase activity precedes by approximately 20 days the increase in testicular capacity to synthesize testosterone in vitro. The latter coincides with the increase in 17β-hydroxysteroid dehydrogenase activity. These results suggest that 17β-hydroxysteroid dehydrogenase is a limiting factor in the ability of the testis to respond to LH stimulation.

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