Effects of modifying gonadotrophin-releasing hormone input before and after the oestrogen-induced LH surge in ovariectomized ewes with hypothalamo-pituitary disconnection

1990 ◽  
Vol 127 (2) ◽  
pp. 223-233 ◽  
Author(s):  
D. J. Phillips ◽  
J. T. Cummins ◽  
I. J. Clarke
Keyword(s):  
Continuous Infusion ◽  
Positive Feedback ◽  
Pulse Amplitude ◽  
Secretory Component ◽  
Similar Response ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Before And After ◽  
Gonadotrophin Releasing Hormone ◽  
Sufficient Magnitude

ABSTRACT The patterns of gonadotrophin-releasing hormone (GnRH) input to the pituitary gland that affect the expression of a positive-feedback event by oestrogen on LH secretion were investigated in ovariectomized ewes with hypothalamo-pituitary disconnection (HPD). In experiment 1, ovariectomized HPD ewes were given hourly i.v. pulses of 250 ng GnRH and an i.m. injection of 50 μg oestradiol benzoate (OB). The ewes were given a bolus pulse of 2·25 μg GnRH 16 h after injection of OB, followed by half-hourly pulses of 250 ng GnRH for 14 h (treatment A). The LH surge response was significantly (P <0·05) greater in these ewes compared with that in ewes given a continuous infusion of GnRH (250 ng/h) after the OB injection, followed by a continuous infusion of 500 ng GnRH/h after the bolus pulse of GnRH (treatment B). When no GnRH was administered after the OB injection, except for the bolus pulse of GnRH (treatment C), the surge response was significantly (P <0·05) reduced compared with that in treatment A, and was reduced compared with treatment B. These data suggest that GnRH pulses are important in the generation of the OB-induced LH surge, but that a baseline secretory component can prime the pituitary to some extent. experiment 2, a doubling of the continuous infusion dose of GnRH used in treatment B to 500 ng/h before the bolus pulse of GnRH and to 1 μg/h afterwards (treatment D) gave a similar response compared with treatment A, suggesting that if the baseline input of GnRH is of sufficient magnitude, it can overcome the lack of pulsatile input. In experiment 3, halving the GnRH pulse amplitude used in treatment A from 250 to 125 ng (treatment E) did not reduce the LH surge response, implying that when the GnRH input is in a pulsatile mode, the amplitude of GnRH pulses is less important than the pulsatile nature per se. In experiment 4, removal of GnRH input after the bolus pulse of GnRH (treatment F) significantly (P <0·05) reduced the surge response compared with when pulses were maintained (treatment A), indicating that GnRH input is still required once the LH surge has been initiated. Collectively, these experiments show that several forms of GnRH delivery, both pulsatile and baseline, can result in the full expression of a positive-feedback response in ovariectomized ewes treated with oestrogen. Journal of Endocrinology (1990) 127, 223–233

The oestrogen-induced surge of LH requires a 'signal' pattern of gonadotrophin-releasing hormone input to the pituitary gland in the ewe

1989 ◽  
Vol 122 (1) ◽  
pp. 127-134 ◽  
Author(s):  
I. J. Clarke ◽  
J. T. Cummins ◽  
M. Jenkin ◽  
D. J. Phillips
Keyword(s):  
Pituitary Gland ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Gnrh Secretion ◽  
Signal Pattern ◽  
Oestradiol Benzoate ◽  
Gonadotrophin Releasing Hormone ◽  
Baseline Values

ABSTRACT Two experiments were conducted with ovariectomized and hypothalamo-pituitary disconnected (HPD) ewes to ascertain the pattern of inputs, to the pituitary gland, of gonadotrophin-releasing hormone (GnRH) necessary for the full expression of an oestrogen-induced LH surge. The standard GnRH replacement to these sheep was to give pulses of 250 ng (i.v.) every 2 h; at the onset of experimentation, pulses were given hourly. In experiment 1, groups of sheep (n = 7) were given an i.m. injection of 50 μg oestradiol benzoate, and after 10 h the GnRH pulse frequency or pulse amplitude was doubled. Monitoring of plasma LH concentrations showed that a doubling of pulse frequency produced a marked increase in baseline values, whereas a doubling of amplitude had little effect on the LH response. In a second experiment, ovariectomized HPD sheep that had received hourly pulses of GnRH for 16 h after an i.m. injection of oil or 50 μg oestradiol benzoate were given either a 'bolus' (2·25 μg GnRH) or a 'volley' (500 ng GnRH pulses 10 min apart for 30 min, plus a 500 ng pulse 15 min later). Both groups then received GnRH pulses (250 ng) every 30 min for the next 13 h. Oestrogen enhanced the LH responses to the GnRH treatments, and the amount of LH released was similar in ovariectomized HPD ewes given oestrogen plus bolus or volley GnRH treatments and ovariectomized hypothalamopituitary intact ewes given oestrogen. These results suggest that the oestrogen-induced LH surge is initiated by a 'signal' pattern of GnRH secretion from the hypothalamus. Journal of Endocrinology (1989) 122, 127–134

Biphasic response in the secretion of gonadotrophin-releasing hormone in ovariectomized ewes injected with oestradiol

1989 ◽  
Vol 123 (3) ◽  
pp. 375-382 ◽  
Author(s):  
A. Caraty ◽  
A. Locatelli ◽  
G. B. Martin
Keyword(s):  
Negative Feedback ◽  
Positive Feedback ◽  
Sampling Period ◽  
Pulse Amplitude ◽  
Portal Blood ◽  
Blood Collection ◽  
Biphasic Response ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

ABSTRACT In ovariectomized ewes, an injection of oestrogen initially inhibits the tonic secretion of LH, and then induces a large release of LH similar to the preovulatory surge in intact ewes. The pattern of hypothalamic secretion of gonadotrophin-releasing hormone (GnRH) into the pituitary portal blood during this biphasic response to oestrogen was investigated in conscious, unrestrained, ovariectomized adult Ile-de-France ewes during the breeding season. The ewes were ovariectomized and implanted with cannulae for portal blood collection on the same day. Seven days later, portal and peripheral blood samples were collected simultaneously every 5 min for 25 h. The ewes were injected with oestradiol-17β (25 μg i.v. and 25 μg i.m.) 6·25 h after the start of sampling. GnRH and LH were measured by radioimmunoassay in portal and jugular plasma samples respectively. A clear pulsatile pattern of LH secretion was observed before the oestradiol injection in all ewes, followed by the typical biphasic decrease (negative feedback) and increase (positive feedback) in mean concentrations. The sampling period was divided, for analysis, into pretreatment, negative feedback and positive feedback phases. Before injection with oestradiol, the GnRH pulses were clearly defined in portal blood and always synchronized with LH pulses in the peripheral circulation. The frequency was 5·9 ± 0·6 pulses/6 h (mean ± s.e.m.), and the amplitude was 31·6±7·6 pmol/l. During negative feedback, both the frequency (4·2 ± 0·5 pulses/6 h, P<0·01) and amplitude (15·2 ± 4·6 pmol/l, P<0·05) of the GnRH pulses decreased. During positive feedback, there was a large surge in the concentration of GnRH, due primarily to an increase in pulse frequency (11·0±1·3 pulses/6 h, P<0·01). A change in pulse amplitude was not detected, but there was a large increase in the basal level of GnRH (P<0·05). As a consequence of the changes in frequency and amplitude of the pulses, the mean levels of GnRH before injection with oestradiol (5·3 ± 1·0 pmol/l) differed (P<0·05) from those during negative (3·8±0·5 pmol/l) and positive (18·9±4·7 pmol/l) feedback phases. These results show that the biphasic pattern of LH secretion induced by oestrogen injection in short-term ovariectomized ewes is caused by parallel changes in the secretion of GnRH as well as changes in pituitary responsiveness to GnRH. An abrupt increase in the frequency of GnRH pulses appears to be a key component of the positive feedback mechanism which elicits the oestradiol-induced surges of both GnRH and LH. Journal of Endocrinology (1989) 123, 375–382

Influence of the characteristics of pulses of gonadotrophin releasing hormone on the dynamics of luteinizing hormone release from perifused sheep pituitary cells

1983 ◽  
Vol 98 (3) ◽  
pp. 411-421 ◽  
Author(s):  
R. P. McIntosh ◽  
J. E. A. McIntosh
Keyword(s):  
Luteinizing Hormone ◽  
Anterior Pituitary ◽  
Pulse Width ◽  
Pulse Amplitude ◽  
Threshold Value ◽  
Pituitary Cells ◽  
Hormone Release ◽  
Releasing Hormone ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

The effects were studied of varying the frequency, width and amplitude of pulses of gonadotrophin releasing hormone (GnRH) on the release of LH from anterior pituitary cells. Dispersed sheep cells supported in Sephadex were perifused with medium for 10 h and stimulated with different constant pulse patterns of GnRH. The timing of release of LH was measured by radioimmunoassay of the effluent fractions. Pulses of GnRH ranging in duration from 2 min every 8 min to 16 min every 128 min, and in concentration from 1·7 pmol/l to 250 nmol/l were applied to the cells, as well as continuous stimulation. Comparisons of differences between LH release patterns among samples of the same preparation of cells were used to demonstrate the effects of different GnRH stimulatory regimes. It was concluded that (1) the frequency of GnRH stimulation was important to the nature of LH release (periods shorter than about 16 min between pulses reduced LH output and caused faster desensitization of response), (2) the pulse width of GnRH input was important (the rising edge of the pulse produced greater LH output per unit of GnRH input than did continued application of GnRH within a pulse and wider pulses combined with shorter periods reduced LH output) and (3) over a threshold value of 5–10 nmol GnRH/1 pulse amplitude had little further influence on LH output or rate of desensitization in dispersed cells. These findings reinforce the hypothesis that the rising edge of the GnRH pulse is the major stimulant to LH release.

Secretion rates and short-term patterns of gonadotrophin-releasing hormone, FSH and LH in the normal stallion in the breeding season

1988 ◽  
Vol 117 (2) ◽  
pp. 197-206 ◽  
Author(s):  
C. H. G. Irvine ◽  
S. L. Alexander
Keyword(s):  
Breeding Season ◽  
Venous Blood ◽  
Pulse Amplitude ◽  
Interpulse Interval ◽  
Statistical Testing ◽  
Pulse Interval ◽  
Apparent Difference ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

ABSTRACT Pituitary venous blood was collected by a painless non-surgical cannulation method from five ambulatory stallions at 5-min intervals for 5–6 h during the breeding season. In four adult stallions, statistical analysis showed that pulses of gonadotrophin-releasing hormone (GnRH) and LH were coincident (P <0·01), as were pulses of FSH and LH (P <0·05). Furthermore, the patterns of changes in concentration of FSH and LH were highly correlated in each of the four stallions. However, seemingly ineffective pulses of GnRH were also observed, with 28% of GnRH pulses failing to induce a significant gonadotrophin pulse. In the four adult stallions the amplitude of pituitary venous gonadotrophin pulses varied markedly but no correlation with GnRH pulse amplitude was observed. Peak secretion of FSH, but not LH, during pulses was correlated with the length of the interpulse interval. Consequently, the ratio of FSH to LH during peaks was least (P <0·02) when the interpulse interval was 30 min or less. Thus, differential FSH and LH secretion was achieved within a constant steroid milieu. Two stallions had regular contact with oestrous mares, and in these horses the secretion of GnRH and gonadotrophins occurred almost continuously with rapid, rhythmic pulses superimposed upon a tonic background. Mean (± s.d.) interval between GnRH pulses was 31·4 ± 9·8 min and 27·7 ± 10·1 min. This secretory pattern was not observed in the two stallions which had infrequent contact with oestrous mares, although the small numbers precluded statistical testing of this apparent difference. No GnRH pulses were observed in one of these stallions, while in the other mean (± s.d.) GnRH pulse interval was 45·0 ± 48·7 min, the large variance being partly due to rapid pulses during a period in which the stallion teased mares. The fifth stallion was pubertal, and GnRH and LH secretion occurred in 15 and 0% of samples respectively, while low levels of FSH secretion were observed in 37% of samples and jugular testosterone levels were immeasurably low. We conclude that there is a statistically significant synchrony between pulses of GnRH, LH and FSH in the pituitary venous blood of stallions. Furthermore, decreasing intervals between gonadotrophin pulses result in a significant reduction in secretion of FSH but not LH. J. Endocr. (1988) 117, 197–206

Feedback effects of gonadal steroids and pituitary LH-releasing hormone receptors in the streptozotocin-induced diabetic rat

1986 ◽  
Vol 111 (4) ◽  
pp. 467-473 ◽  
Author(s):  
P. A. Bowton ◽  
K. R. Bryant ◽  
S. A. Whitehead
Keyword(s):  
Positive Feedback ◽  
Hormone Receptors ◽  
Gonadal Steroids ◽  
Diabetic Rat ◽  
High Dose ◽  
Feedback Effects ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Long Acting ◽  
Lh Releasing Hormone

Abstract. The effects of streptozotocin (STZ)-induced diabetes mellitus on the positive feedback action of steroids on luteinizing hormone (LH) secretion have been investigated in the oestrogen-primed ovariectomized rat. Rats treated with 40 mg/kg STZ 2 weeks before experimentation showed an attenuated LH surge in response to progesterone, an effect only partially restored by insulin replacement. When the same dose of the drug was injected just 24 h before the progesterone treatment it had no effect on the LH surge, while a high dose of 80 mg/kg STZ completely abolished the positive feedback action of the steroid. Insulin treatment did not reverse this effect. In parallel the effects of 2-week and 24-h diabetes on pituitary LH-releasing hormone (LRH) receptors were studied. Pituitary binding of a long acting LRH analogue was reduced in the 2-week diabetic animals, although a more dramatic reduction was observed in the rats treated with the high dose of STZ 24 h before testing. The results suggest that diabetes impairs the positive feedback effects of gonadal steroids resulting in a reduced release of LRH. However, the impairment is unlikely to be caused simply by hyperglycaemia but by non-specific toxic side effects of STZ and/or other metabolic changes associated with diabetes.

Gonadotrophin-releasing hormone secretion (GnRH) in anoestrous ewes and the induction of GnRH surges by oestrogen

1988 ◽  
Vol 117 (3) ◽  
pp. 355-360 ◽  
Author(s):  
I. J. Clarke
Keyword(s):  
Hormone Secretion ◽  
Sampling Period ◽  
Pulse Frequency ◽  
Marked Rise ◽  
Oestrogen Treatment ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Gnrh Secretion ◽  
Gonadotrophin Releasing Hormone ◽  
Large Pulse

ABSTRACT Anoestrous ewes were studied to determine the pattern of secretion of gonadotrophin-releasing hormone (GnRH) in the resting state and following a single i.m. injection of 50 μg oestradiol benzoate. In three out of four untreated ewes, two or three GnRH pulses were observed over a 6-h sampling period. In the fourth sheep the GnRH pulse frequency was higher (six pulses/6 h), but GnRH pulse amplitudes were lower. Following oestrogen treatment, GnRH pulses continued until the occurrence of an LH surge 12 h later. In five out of six sheep sampled during the oestrogen-induced LH surge a marked rise in GnRH secretion was seen. In the sixth ewe a large pulse of GnRH was seen at the start of the LH surge followed by increased GnRH secretion. It is concluded that GnRH pulse frequency is lower, generally, during anoestrus than during the mating season, and that oestrogen treatment of anoestrous ewes causes a surge in GnRH secretion unlike that seen in similarly treated ovariectomized ewes or the natural cyclic preovulatory changes in GnRH secretion. J. Endocr. (1988) 117, 355–360

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.

The significance of small pulses of gonadotrophin-releasing hormone

1987 ◽  
Vol 113 (3) ◽  
pp. 413-418 ◽  
Author(s):  
I. J. Clarke ◽  
J. T. Cummins
Keyword(s):  
Pulse Amplitude ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Series Of Experiments

ABSTRACT A series of experiments was conducted to ascertain the significance of 'small' pulses of gonadotrophin-releasing hormone (GnRH). In the first experiment, ovariectomized hypothalamo-pituitary disconnected (HPD) ewes were given 250 ng pulses of GnRH every 2 h for 1 week, 25 ng pulses every 2 h for 24 h, 25 ng pulses hourly for 24 h and then alternating hourly pulses of 25 and 250 ng. During the 25 ng pulses, LH was not detectable in plasma and FSH concentrations declined after 2 days. Following the 25 ng pulses, the resumption of 250 ng pulses led to exaggerated LH responses (mean ± s.e.m. pulse amplitude 18·7 ± 1·7 vs 10·2 ± 1·2 μg/l in the first week). In a second experiment, ovariectomized–HPD ewes were maintained on 250 ng GnRH pulses every 2 h for 1 week and were then given three 25 ng pulses mid-way between the 250 ng pulses. Samples of blood were taken over three 250 ng pulses without 25 ng insertions and over three pulses with insertions. The insertion of 25 ng GnRH pulses did not cause LH pulses in their own right and did not alter the LH responses to the 250 ng pulses. In a third experiment, 50 ng GnRH pulses were inserted between the 250 ng GnRH pulses, as in experiment 2; these 50 ng pulses caused small LH pulses and led to a reduction in the response of the LH pulse amplitude to the 250 ng pulses. The 'small' LH pulses which occurred in response to 50 ng GnRH compensated for the reduced responses to the 250 ng pulses. Hence, the integrated area under the LH curve and between successive 250 ng pulses remained the same, irrespective of the 50 ng insertions. From these data we conclude that 'small' GnRH pulses alone can sustain ongoing LH synthesis without release, leading to an accumulation of releasable LH, and that the insertion of 'small' GnRH pulses may modify the pattern of pituitary responsiveness to 'large' GnRH pulses. J. Endocr. (1987) 113, 413–418

Effect of hypothyroidism on the pituitary-gonadal axis in the adult female rat

1995 ◽  
Vol 146 (1) ◽  
pp. 87-94 ◽  
Author(s):  
J A M Mattheij ◽  
J J M Swarts ◽  
P Lokerse ◽  
J T van Kampen ◽  
D Van der Heide
Keyword(s):  
Thyroid Hormone ◽  
Adult Female ◽  
Ovulation Rate ◽  
Female Rats ◽  
Corpora Lutea ◽  
Female Rat ◽  
Plasma Progesterone ◽  
Lh Surge ◽  
Before And After ◽  
Gonadotrophin Releasing Hormone

Abstract The pituitary-ovarian axis was studied after withdrawal of thyroid hormone in 131I-radiothyroidectomized adult female rats. Oestrous cycles became prolonged and irregular within 2 weeks after the supply of thyroid hormone was stopped. If an LH surge occurred in hypothyroid rats on the day of vaginal pro-oestrus it was significantly greater in rats which had been made hypothyroid for 4–5 weeks than in controls; in hypothyroid rats with an LH surge on pro-oestrus, plasma progesterone showed a rise similar to that in controls at pro-oestrus; the ovulation rate was decreased in hypothyroid rats. About half of the rats from which blood was sampled daily in the afternoon between 7 and 18 days after tri-iodothyronine (T3) withdrawal had 1 day of pro-oestrus; on this day the LH surge was higher than in controls. On days 2 and 1 before and days 1 and 2 after this pro-oestrus, plasma progesterone was similar to that of controls on days 2 and 1 before and days 1 and 2 after pro-oestrus respectively. However, progesterone was higher in the period before and after these days. The other hypothyroid rats showed no pro-oestrus and no LH surge during this period, while their plasma progesterone levels were high on all days. On the morning of day 10 after T3 withdrawal and 5 days after the preceding pro-oestrus, most hypothyroid rats had high progesterone and low oestradiol plasma levels. In these rats, injection of gonadotrophin-releasing hormone caused a relatively small increase in LH; it did not stimulate the secretion of oestradiol or progesterone, and it did not induce ovulation. It was concluded that hypothyroidism induces major changes in the secretion of steroids by corpora lutea and growing follicles. Whether the changed steroid metabolism is the primary cause of the observed prolongation of the oestrous cycles, the increased pro-oestrous LH surge and the reduced ovulation rate remains to be investigated. Journal of Endocrinology (1995) 146, 87–94

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