Blockade of LH and FSH secretion by LH-releasing hormone, by the LH-releasing hormone analogue, buserelin, and by combined treatment with LH-releasing hormone and oestradiol benzoate

ABSTRACT The LH and FSH release-stimulating (experiment 1) and -blocking (experiment 2) effects of LH-releasing hormone (LHRH) and of the LHRH analogue d-Ser(But)6-des-Gly10-LHRH-ethylamide (buserelin), as well as the effect of combined treatment with LH RH and oestradiol benzoate (OB; experiment 3) on the 'supra-maximally' LHRH-stimulated release of LH and FSH were studied in rats ovariectomized for 2 weeks. Pretreatment with LHRH (250 or 500 ng/h) or buserelin (250 ng/h) for 6 days was effected by means of subcutaneously implanted Alzet osmotic minipumps; control rats received a 'sham pump', i.e. a piece of silicone elastomer with the dimensions of a minipump. Oestradiol benzoate (3 μg/injection) or solvent was injected subcutaneously 75 and 27 h before the induction of LH/FSH responses. Experiment 1 revealed that after infusion of LHRH and buserelin, both at the rate of 1 μg/h, plasma LHRH concentrations were established which were about twice as low as the plasma buserelin concentrations. This might suggest that buserelin has a longer half-life than LHRH. As an LH and FSH release-stimulating substance, however, it appeared that buserelin was about as effective as LHRH. Experiment 2, however, suggested that as an LH/FSH release-blocking agent buserelin was much more effective than LHRH. In addition, after buserelin pretreatment the pituitary glands contained much less LH and FSH than after LHRH pretreatment at both dose levels used. However, this may also (at least partly) be due to the fact that buserelin has a longer half-life so that after infusion of buserelin and LHRH at the same rate the plasma concentrations of buserelin are higher than those of LHRH; after buserelin infusion the pituitary gland is therefore stimulated at a higher intensity. Experiment 3 showed that in OB-injected, sham-implanted rats the LHRH-stimulated secretion of LH and FSH was significantly higher than in the oil-injected, sham-implanted rats. In the LHRH-pretreated rats (LHRH: 250 ng/h for 6 days), however, the already depressed LHRH-stimulated secretion of LH and FSH was still further depressed by OB treatment. These latter results suggest that the increase of the pituitary LHRH responsiveness during exposure to oestrogen requires a reduction of the LHRH stimulation, which is normally caused by the negative feedback of oestrogen on the hypothalamus. J. Endocr. (1984) 103, 301–309

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LUTEINIZING HORMONE RELEASING HORMONE-INDUCED RELEASE OF LUTEINIZING HORMONE FROM PITUITARY EXPLANTS OF COWS KILLED BEFORE OR AFTER OESTRADIOL TREATMENT

Journal of Endocrinology ◽

10.1677/joe.0.0880017 ◽

1981 ◽

Vol 88 (1) ◽

pp. 17-25 ◽

Cited By ~ 9

Author(s):

E. M. CONVEY ◽

J. S. KESNER ◽

V. PADMANABHAN ◽

T. D. CARRUTHERS ◽

T. W. BECK

Keyword(s):

Luteinizing Hormone ◽

Pituitary Gland ◽

Lh Surge ◽

Releasing Hormone ◽

Oestradiol Treatment ◽

Readily Releasable Pool ◽

Serum Lh ◽

Pituitary Glands ◽

Lh Rh ◽

Lh Releasing Hormone

In ovariectomized heifers, oestradiol decreases concentrations of LH in serum for approximately 12 h after which LH is released in a surge comparable in size and duration to the preovulatory surge. Using this model, we measured LH release induced by LH releasing hormone (LH-RH) from pituitary explants taken from ovariectomized heifers before or after an oestradiol-induced LH surge. These changes were related to changes in LH concentrations in serum and pituitary glands and hypothalamic LH-RH content. Twenty Holstein heifers were randomly assigned to one of four treatment groups to be killed 0, 6, 12, or 24 h after the injection of 500 μg oestradiol-17β. Jugular blood was collected at −2, −1 and 0 h then at intervals of 2 h until slaughter. Pituitary glands were collected and ≃2 mm3 explants were exposed to 4 ng LH-RH/ml medium for 30 min (superfusion) or 4 ng LH-RH/ml medium for 2 h in Erlenmeyer flasks. Levels of LH were measured in the medium. Hypothalami, collected at autopsy, were assayed for LH-RH content. To determine pituitary LH content, an additional 15 ovariectomized heifers were killed, five each at 0, 12 and 24 h after the injection of 500 μg oestradiol. In both groups of heifers, oestradiol reduced serum LH concentrations to ≃ 1 ng/ml, a level which persisted for 12 h, when LH was released in a surge. Pituitary sensitivity to LH-RH was increased at 6 and 12 h after the injection of oestradiol, but was markedly decreased at 24 h, i.e. after the LH surge. Despite this twofold increase in capacity of the pituitary gland to release LH in response to LH-RH, pituitary LH content did not change during 12 h after oestradiol treatment. However, LH content decreased after the LH surge and this decrease was associated with a decrease in pituitary responsiveness to LH-RH. Hypothalamic LH-RH content was not altered by these treatments. We have interpreted our results as evidence that oestradiol exerts a positive feedback effect on the pituitary gland of ovariectomized heifers such that pituitary sensitivity to LH-RH is increased twofold by the time the LH surge is initiated. In addition, oestradiol causes a transitory inhibition of LH-RH release as shown by the fact that serum LH concentrations remained low during the interval from injection of oestradiol until the beginning of the LH surge despite the fact that pituitary sensitivity to LH-RH is increased at this time. Depletion of a readily releasable pool of pituitary LH may be the mechanism by which the LH surge is terminated.

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DISSOCIATION IN THE REGULATION OF LUTEINIZING HORMONE AND FOLLICLE-STIMULATING HORMONE IN A HYPERPROLACTINAEMIC RAT MODEL: INTERRELATIONSHIPS BETWEEN GONADOTROPHIN AND PROLACTIN CONTROL

Journal of Endocrinology ◽

10.1677/joe.0.0900041 ◽

1981 ◽

Vol 90 (1) ◽

pp. 41-51 ◽

Cited By ~ 39

Author(s):

J. A. F. TRESGUERRES ◽

A. I. ESQUIFINO

Keyword(s):

Positive Feedback ◽

Follicle Stimulating Hormone ◽

Female Rats ◽

Male And Female ◽

Male And Female Rats ◽

Oestradiol Benzoate ◽

Female Wistar Rats ◽

Pituitary Glands ◽

Lh Rh ◽

Lh Releasing Hormone

Male and female Wistar rats were made hyperprolactinaemic by grafting two pituitary glands of litter-mate donors under the kidney capsule at 30 days of age. Other animals were sham-operated at the same age to serve as controls. Plasma levels of prolactin, LH and FSH were measured by double-antibody radioimmunoassay. Basal preoperative prolactin levels of ∼ 10 ng/ml increased after the transplantation in both male and female rats, reaching values of ∼ 180 ng/ml. Levels of LH were significantly reduced in these hyperprolactinaemic rats, whereas an increase in FSH values was seen. After administration of LH releasing hormone (LH-RH) a reduced LH response was seen but there was no response of FSH to LH-RH or even a decrease in FSH values. Prolactin levels were also reduced by LH-RH injection. Although an increase in prolactin levels was observed in control animals after a challenge with oestradiol benzoate, reduced increments were seen in experimental animals. The positive feedback effect of oestradiol benzoate on LH in females was reduced in pituitary-grafted rats but a potentiation of the FSH positive feedback could be clearly detected. This study suggests a dissociation of LH and FSH regulation in hyperprolactinaemia.

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DEPENDENCE ON PROTEIN SYNTHESIS OF THE N6-MONOBUTYRYL CYCLIC AMP PLUS THEOPHYLLINE MEDIATED RELEASE OF LUTEINIZING HORMONE INDUCED BY LUTEINIZING HORMONE RELEASING HORMONE FROM RAT PITUITARY GLANDS IN VITRO

Journal of Endocrinology ◽

10.1677/joe.0.0880329 ◽

1981 ◽

Vol 88 (3) ◽

pp. 329-338 ◽

Cited By ~ 10

Author(s):

J. DE KONING ◽

J. A. M. J. VAN DIETEN ◽

A. M. I. TIJSSEN ◽

G. P. VAN REES

Keyword(s):

Protein Synthesis ◽

Luteinizing Hormone ◽

Cyclic Amp ◽

Female Rats ◽

Releasing Hormone ◽

Pituitary Tissue ◽

Pituitary Glands ◽

Lh Release ◽

Lh Rh ◽

Lh Releasing Hormone

The involvement of cyclic AMP in the action of LH releasing hormone (LH-RH) on LH secretion was studied by incubating pituitary glands from adult female rats on day 2 of dioestrus with 1 mm-N6-monobutyryl cyclic AMP (mbcAMP) and 10 mm-theophylline for periods of up to 10 h. This treatment induced a pattern of LH release similar to that observed in the presence of a low concentration of LH-RH (0·1 ng LH-RH/ml), i.e. an initial 4 h period during which the release of LH was minimal was followed subsequently by an increased rate of release. In this system inhibition of protein synthesis by cycloheximide (25 μg/ml) did not impair the initial response of the pituitary tissue but the increase in the rate of LH release during the second phase of the response was blocked. Preincubation with mbcAMP and theophylline increased the responsiveness of the pituitary tissue to LH-RH. This action could be prevented by including cycloheximide during the preincubation period, whereas addition of this drug during the incubation with LH-RH no longer impaired the increased responsiveness. The size of the sensitizing action of mbcAMP and theophylline mediated through the induction of protein synthesis was comparable with that of a high concentration of LH-RH. From the absence of a significant change in total LH during the preincubation period, it was concluded that the increased responsiveness was not the result of newly synthesized LH. The present results suggest a role or roles for cyclic AMP in the secretion of LH induced by LH-RH. Besides an effect on the formation of a factor related to the synthesis of protein, other than LH which has a permissive role in the acute release of LH, cyclic AMP might also be concerned in the secretion process through a pathway which does not involve synthesis of protein.

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Priming effect of luteinizing hormone releasing hormone in the hypogonadal mouse

Journal of Endocrinology ◽

10.1677/joe.0.0940283 ◽

1982 ◽

Vol 94 (2) ◽

pp. 283-287 ◽

Cited By ~ 16

Author(s):

G. Fink ◽

W. J. Sheward ◽

H. M. Charlton

Keyword(s):

Luteinizing Hormone ◽

Pituitary Gland ◽

Priming Effect ◽

Plasma Concentrations ◽

Luteinizing Hormone Releasing Hormone ◽

Releasing Hormone ◽

Lh Rh ◽

Lh Releasing Hormone

We have investigated the LH response to LH releasing hormone (LH-RH) in female hypogonadal (hpg) mice in which the hypothalamus contains no LH-RH and the pituitary gland contains significantly less LH than in normal mice. Both the releasing action and the priming effect of LH-RH were not significantly different in hpg compared with normal mice. Raised plasma concentrations of oestradiol-17β reduced pituitary responsiveness to LH-RH in normal but not in hpg mice. These results show that in the mouse neither longterm exposure to normal levels of LH-RH nor a normal pituitary content of LH are necessary for either the releasing or the priming action of LH-RH.

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IMMATURE RAT PITUITARY GLANDS IN VITRO: AGE- AND SEX-RELATED CHANGES IN LUTEINIZING HORMONE RELEASING HORMONE-STIMULATED GONADOTROPHIN RELEASE

Journal of Endocrinology ◽

10.1677/joe.0.0730309 ◽

1977 ◽

Vol 73 (2) ◽

pp. 309-319 ◽

Cited By ~ 12

Author(s):

J. DULLAART

Keyword(s):

Male Rats ◽

Steady Increase ◽

Releasing Hormone ◽

Rat Pituitary ◽

Pituitary Glands ◽

Lh Release ◽

The One ◽

Lh Rh ◽

Lh Releasing Hormone

SUMMARY Pituitary glands from immature female and male rats aged between 5 and 30 days were incubated in vitro and the effect of LH releasing hormone (RH) on the release of LH and FSH was studied. Pituitary gonadotrophin contents were also measured. Gonadotrophin release showed changes with age as well as sex differences: after LH-RH stimulation the female pattern of release of LH and FSH (expressed per mg pituitary tissue) showed a peak at day 15; the male pattern of LH release was characterized by a steady increase with age, whereas FSH release stayed more or less constant from day 10 onwards. In both sexes the LH:FSH ratio increased with age, both in pituitary gonadotrophin content and in the mixture of gonadotrophins released. It is discussed, that the prepubertal development of pituitary gonadotrophic function might be determined on the one hand by rather autonomous growth processes (more or less similar in female and male hypophyses) and on the other hand by modulating influences of sex steroid hormones, which are different in female and male animals.

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EFFECT OF 20α-HYDROXYY-4-PREGNEN-3-ONE ON LUTEINIZING HORMONE SECRETION IN THE FEMALE RABBIT

Acta Endocrinologica ◽

10.1530/acta.0.0840045 ◽

1977 ◽

Vol 84 (1) ◽

pp. 45-50 ◽

Cited By ~ 2

Author(s):

E. V. YoungLai

Keyword(s):

Luteinizing Hormone ◽

Hormone Secretion ◽

Luteinizing Hormone Secretion ◽

Releasing Hormone ◽

Female Rabbit ◽

Oestradiol Benzoate ◽

Lh Rh ◽

Lh Releasing Hormone ◽

Lh Secretion

ABSTRACT Experiments were performed in the rabbit to determine whether 20α-hydroxy-4-pregnen-3-one (20-OHP) can maintain luteinizing hormone (LH) secretion after injections of LH-releasing hormone (LH-RH). Female rabbits were castrated at least 2 weeks prior to investigation. On the day before LH-RH injection they were cannulated and a dose of oestradiol benzoate (OeB), 100 μg/kg, given intramuscularly. LH-RH, 500 ng/kg, was injected as a bolus via the cannula and 20-OHP, 100 μg/kg and 2.5 mg/kg, injected intramuscularly immediately after. Blood was withdrawn at intervals for up to 5½ h after LH-RH injection. LH secretion dropped to pre-stimulation levels within 3 h after LH-RH alone or in combination with 20-OHP. Administration of LH-RH to oestrogen primed intact females also gave a peak of LH which returned to pre-stimulation levels within 3 h. However, mating seemed to maintain LH levels for a greater period of time.

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USE OF A PULSED INFUSION OF LUTEINIZING HORMONE RELEASING HORMONE TO MIMIC SEASONALLY INDUCED ENDOCRINE CHANGES IN THE RAM

Journal of Endocrinology ◽

10.1677/joe.0.0830251 ◽

1979 ◽

Vol 83 (2) ◽

pp. 251-260 ◽

Cited By ~ 18

Author(s):

G. A. LINCOLN

Keyword(s):

Plasma Concentrations ◽

Prolonged Treatment ◽

Mating Season ◽

Releasing Hormone ◽

Natural Lighting ◽

Sexual Skin ◽

Gonadotrophin Secretion ◽

The Individual ◽

Lh Rh ◽

Lh Releasing Hormone

Adult Soay rams were housed indoors under natural lighting during the spring non-mating season when gonadotrophin secretion was low. Four animals received small doses (100 ng or 500 ng) of synthetic LH releasing hormone (LH-RH) infused into the jugular vein by a mechanical device for 60 s every 2 h for 33–57 days: two other rams acted as controls. The prolonged treatment with LH-RH resulted in growth of the testes and the development of the sexual skin flush; these effects were lost when treatment stopped. The plasma concentrations of LH, FSH and testosterone were low at the beginning; each short infusion of LH-RH resulted in a transitory increase in the level of LH and testosterone while the concentration of FSH was only marginally affected. After prolonged treatment with 500 ng pulses of LH-RH the plasma concentrations of all three hormones were permanently raised. The response to the individual injections of LH-RH was also modified, the peak in LH being reduced in amplitude but more prolonged while the FSH and testosterone responses were both enhanced. When the pulsed infusion was stopped the concentration of LH and testosterone declined rapidly while the decline in FSH levels took many days. These endocrine changes induced by the pulsed infusion are comparable to those that occur naturally in the ram during testicular redevelopment before the mating season.

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EFFECT OF CORTISOL OR ADRENOCORTICOTROPHIN ON RELEASE OF LUTEINIZING HORMONE INDUCED BY LUTEINIZING HORMONE RELEASING HORMONE IN THE DAIRY HEIFER

Journal of Endocrinology ◽

10.1677/joe.0.0920141 ◽

1982 ◽

Vol 92 (1) ◽

pp. 141-146 ◽

Cited By ~ 26

Author(s):

R. L. MATTERI ◽

G. P. MOBERG

Keyword(s):

Luteinizing Hormone ◽

Luteinizing Hormone Releasing Hormone ◽

Releasing Hormone ◽

Dairy Heifers ◽

Significant Difference ◽

Significant Depression ◽

Lh Rh ◽

Lh Releasing Hormone ◽

And Control ◽

Slight Depression

During treatment with cortisol or ACTH, dairy heifers were given two doses of LH releasing hormone (LH-RH) spaced 1·5 h apart. Serum concentrations of cortisol and LH were monitored during each treatment. Treatment with both ACTH and cortisol raised plasma cortisol levels above the respective saline controls (P<0·001). Neither treatment affected basal LH concentrations. A slight depression in LH response was seen in the cortisol-treated animals after the first LH-RH injection, as shown by a statistically significant depression at three of the sample times. There was no significant difference between treated and control LH values after the second LH-RH administration. Treatment with ACTH resulted in significantly reduced LH values at all sample times after both injections of LH-RH.

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