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T R Koiter

Publications and source records attributed to T R Koiter.

At least 55 records · Page 3Linked to original sources

Clomiphene citrate can mimic the augmentative (positive) but not the depressing (negative) effect of estradiol on the LHRH-stimulated release of LH and FSH by the pituitary gland of the long-term ovariectomized rat.

In the long-term ovariectomized rat, both estradiol benzoate (EB) and clomiphene citrate enhance the release of LH induced by luteinizing hormone-releasing hormone (LHRH). EB also enhances the release of FSH. In rats pretreated with LHRH, EB strongly depresses the LHRH-induced LH/FSH release, but clomiphene enhances this release, regardless of the presence of EB.

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Progesterone and the control of functional luteolysis, of secretion of prolactin and of pituitary LHRH responsiveness. A study with pseudopregnant rats kept in alternating and constant lighting conditions.

The effect of exogenous progesterone (P) on the corpus luteum function (in terms of the secretion of P and 20-alpha-dihydroprogesterone (DHP), on the secretion of prolactin (Prl) and on the pituitary responsiveness to LHRH was studied in pseudopregnant (PSP) rats kept in alternating and constant lighting conditions (LD-PSP and LL-PSP rats, respectively). Rats were rendered pseudopregnant by appropriately timed stimulation of the cervix uteri (LL rats first received an ovulatory dose of hCG). LH responses were induced by constant rate infusion of LHRH (104 ng/h for 21 h). P was delivered by subcutaneously inserted Silastic implants; control rats received sham implants. In both LD-and LL-PSP rats the plasma P and DHP levels were high on day 8 of PSP. On day 12, however, the plasma P levels had fallen but the DHP levels had risen, demonstrating that between days 8 and 12 functional luteolysis had occurred and that neither the production of P and DHP, nor the timing of luteolysis are under the control of the lighting conditions. On day 12 of PSP the pituitary responsiveness to LHRH was much higher than on day 8. Moreover, on days 8/9 of PSP peaks of Prl were seen in all rats, but on days 11/12 such peaks were largely absent. In LD-PSP rats 'nocturnal' Prl peaks were seen on days 8/9 in all 9 experimental animals, but 'diurnal' peaks were seen in only 4 of these animals. Also, the diurnal peaks were on average much lower than the nocturnal peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

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The depressing (negative) effect of oestradiol benzoate on the in vitro secretion of LH and FSH by the pituitary gland of the LRH-pretreated long-term ovariectomized rat changes into the augmentative (positive) effect after discontinuation of the LRH-pretreatment.

The effect of pretreatment in vivo with oestradiol benzoate on in vitro secretion of LH and FSH was studied in long-term ovariectomized (OVX) rats both at the end of a 5-day continuous in vivo pretreatment with LRH and 4-days after cessation of such LRH pretreatment. Rats were on day 0 sc implanted with osmotic minipumps which released LRH at the rate of 250 ng/h. Control rats were implanted with a piece of silicone elastomer with the dimensions of a minipump. On days 2 and 4 the rats were injected with either 3 micrograms EB or with oil. On day 5 part of the rats were decapitated and the in vitro autonomous (i.e. non-LRH-stimulated) and 'supra-maximally' LRH-stimulated release of LH and FSH was studied using a perifusion system. From other rats the minipumps were removed on day 5 and perifusion was performed on day 9. On the 5th day of the in vivo LRH pretreatment the pituitary LH/FSH stores were partially depleted; the pituitaries of the EB-treated rats more so than those of the oil-injected rats. EB alone had no significant effect on the content of the pituitary LH- and FSH stores. On day 9, i.e. 4 days after removal of the minipumps, the pituitary LH and FSH contents had increased in both the oil- and the EB injected rats, but had not yet recovered to control values. In rats not subjected to the 5-days pretreatment with LRH EB had a positive effect on the supra-maximally LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. EB had no effect on the non-stimulated secretion of FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

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Comparison between the biological effects of LH-RH and buserelin on the induction of LH release from hemi-pituitary glands of female rats in vitro.

The biological effects of LH-RH and the agonist [D-Ser(But)6-des Gly10]-LH-RH(1-9)-ethylamide (buserelin) were compared during 8 h of incubation with female rat hemi-pituitary glands. Similar dose-response relationships were found for LH-RH and buserelin as concerns the release of luteinizing hormone (LH) by pituitary glands from intact and ovariectomized rats. Also the LH secretion patterns from glands of intact rats were similar: an initial low response was followed by a fast increase (priming effect) after which the response declined again (desensitization). In a subsequent experiment pituitary glands from ovariectomized rats were first exposed to LH-RH or buserelin for 4 h and then further incubated in medium only. After discontinuation of the stimuli the rate of LH release decreased in all cases, but this decrease was significantly greater when the glands had been exposed to LH-RH. Short-term (1/2, 1 or 2 h) exposures to LH-RH or buserelin followed by an intervening period (1 1/2, 1 or 0 h, respectively) of incubation in medium only resulted in an almost similar, significant increase in the subsequent protein synthesis-independent LH response to LH-RH (priming effect). Only preincubation with LH-RH for 2 h was significantly more effective. The results demonstrate equal intrinsic activities for LH-RH and buserelin. Differences in the biopotencies for LH-RH and buserelin in vivo and in vitro may occur only after discontinuation of the external stimuli.

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A comparison of the LH-releasing activities of LH-RH and its agonistic analogue buserelin in the ovariectomized rat.

LH-RH and the potent agonistic analogue (D-Ser(But)6-des-Gly10)-LH-RH(1-9)-ethylamide (HOE-766 or buserelin) were at several doses either infused or injected intravenously in 5-weeks-ovariectomized rats, which had been treated with either 3 micrograms estradiol-benzoate (EB) or with oil, 24 h previously. Blood samples for assay of LH were taken during the subsequent 24 h. Pituitary glands were removed at the end of the experiments. Buserelin, when infused, was slightly more effective than LH-RH on releasing LH. When injected, however, buserelin was at the higher dose ranges increasingly more effective as an LH-releasing agent than LH-RH. EB-treatment increased the LH response of the pituitary gland to both peptides in an identical way. It was concluded that buserelin derives its high potency not from its intrinsic LH-releasing activity, which is only slightly greater than that of LH-RH, but from a longer duration of action.

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Prolonged combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and oestradiol benzoate causes long-lasting suppression of the autonomous and the LRH-stimulated secretion of luteinizing hormone and follicle stimulating hormone. An in vitro study.

The effect of a combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and oestradiol benzoate (EB) on the autonomous and the 'supra-maximally' LRH-stimulated in vitro release of LH and FSH by pituitary glands of 2 weeks ovariectomized (OVX) rats was studied using a perifusion system. The concentration of LRH in the perifusion medium was 1 microgram/ml. Pre-treatment with LRH during 6 days was effected by means of sc implanted Alzet osmotic minipumps (MP). Control rats received a piece of silastic with the dimensions of a minipump ('sham-pump'; Sh-P). EB, 3 micrograms/injection or solvent (arachis oil) was sc injected on days-3 and -1 (day of perifusion: day 0). Of the pituitary glands of EB-injected, Sh-P-implanted rats both the autonomous and the LRH-stimulated secretion of LH and the LRH-stimulated secretion of FSH were significantly higher than those of the oil-injected, Sh-P-implanted rats without EB administration. Pretreatment with LRH for 6 days had a suppressing effect on the autonomous and the LRH-induced depletion of the pituitary LH and FSH stores. In combination with EB, the suppressing effect of LRH pre-treatment on the LRH-stimulated secretion of LH and FSH was still greater: the pituitary gland appeared to be fixed in a relatively unresponsive state with very low autonomous LH and FSH secretion. It is discussed that increase of pituitary LRH-responsiveness due to EB demands withdrawal of the pituitary gland from the influence of LRH, an effect which is in vivo achieved by the negative feedback of oestrogen on the hypothalamus.

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Desensitization of the pituitary gland induced in vivo by luteinizing hormone-releasing hormone (LRH) or by the LRH-analogue buserelin does not affect the autonomous secretion of luteinizing hormone and follicle stimulating hormone as observed in vitro.

Three-weeks ovariectomized rats were sc implanted with Alzet osmotic minipumps which released either LRH or the LRH-analogue buserelin at the rate of 250 ng/h. Control rats were implanted with a silastic 'shampump'. After explantation, 6 days later, the pituitary glands of part of these rats were exposed to the maximally active LRH concentration of 1 micrograms/ml for a period of 6 h, using a perifusion system. In a second group of rats explantation and perifusion was done not directly, but 5 days after cessation of the LRH pre-treatment. After 6 days in vivo pre-treatment with LRH or with buserelin the pituitary LH and FSH stores were partially depleted, the depletion after buserelin being stronger than after LRH. The pituitary glands of the first group of rats showed rates of both maximally LRH-stimulated and unstimulated (autonomous) LH- and FSH-secretion which were strongly impaired, the impairment after buserelin being stronger than after LRH. In the group with a 5 days interval between in vivo LRH/buserelin pre-treatment and explantation the pituitary LH and FSH stores were restored to the range of pre-treatment levels. Of these pituitaries the autonomous secretion of LH and FSH as well as the maximally LRH-stimulated secretion of FSH was restored to the normal level; the maximally LRH-stimulated secretion of LH, however, remained depressed, indicating that 5 days after cessation of exposure to LRH or to buserelin, and in spite of restored pituitary LH/FSH contents, the sensitivity of the LH releasing system to LRH was still subnormal.(ABSTRACT TRUNCATED AT 250 WORDS)

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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.

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 LHRH 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 micrograms/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 microgram/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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Control of follicle-stimulating hormone secretion by steroid-free bovine follicular fluid in the ovariectomized rat.

The effects of steroid-free bovine follicular fluid (bFF) and sodium phenobarbitone on spontaneous LH releasing hormone (LHRH)-induced secretion of FSH and LH were studied in ovariectomized rats. Luteinizing hormone releasing hormone was administered by infusion to rats anaesthetized with phenobarbitone. Bovine follicular fluid reduced FSH release and synthesis. Luteinizing hormone release remained unaffected after bFF treatment. Phenobarbitone reduced both FSH and LH release. The observed suppressive effects of bFF and phenobarbitone on FSH secretion were additive, suggesting that the basal release of FSH has an LHRH-dependent and an LHRH-independent component. Furthermore, bFF did not affect pituitary responsiveness of LH secretion to LHRH and reduced the responsiveness of FSH secretion only when administered some time before the LHRH challenge. The present observations support the view that in the ovariectomized rat the pituitary gland is the only site of action of inhibin-like activity as present in bFF.

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Changes in pituitary LH content and LH secretion in the long-term ovariectomized rat during prolonged infusion of LRH.

LH secretion and the depletion of the pituitary LH stores caused by continuous infusion of LRH, were studied in the 5-weeks ovariectomized rat. After 1 day of infusion at the rate of 416 ng/h, pituitary LH content decreased to about 40% of its initial value. Upon continuation of the infusion the LH content increased slowly until, after 7 days, it increased to about 54% of the original value. The plasma LH concentrations, after having reached peak values of 7122 +/- 291 ng/ml after 2 h of infusion, declined to a plateau at about 300 ng/ml but it took 5 days to reach this value. When after either 2 or 8 days of LRH infusion at the rate of 416 ng/h the infusion was changed to a 'supramaximal' rate of 10,400 ng/h for 24 h, a transient secondary rise of LH secretion was induced. The magnitude of the secondary response, was essentially the same after 2 or 8 days of LRH infusion, but these secondary responses were significantly smaller than the LH-response during a similar LRH-infusion in previously untreated ovariectomized rats.

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Recovery of the pituitary gland from LRH-induced refractoriness to LRH in the ovariectomized rat.

Recovery of the pituitary gland from LRH-induced refractoriness to LRH was studied in 5-weeks ovariectomized rats. Rats first received over a period of 48 h an infusion of LRH at a rate of 416 ng/h. After discontinuation of this infusion pituitary LH content had decreased to about 50% of its original value and the rate of LH secretion decreased markedly. Over a period of 72 h after discontinuation of the infusion plasma LH values rose to pre-infusion values but pituitary LH content showed such a recovery only partly. In another series of experiments a second infusion of LRH was given during 24 h and again at a rate of 416 ng/h, starting 3, 12, 24 or 72 h after discontinuation of the first infusion. It induced rises of LH secretion which were smaller than those following the first infusion, indicating refractoriness of the pituitary gland to LRH. However, the LH responses became progressively larger with increasing time intervals after the end of the first infusion. This stimulation of LH release was accompanied by a further decrease of pituitary LH content which was still depressed after the first infusion. Comparison of plasma LH levels and pituitary LH content indicated that pituitary responsiveness to LRH can recover independently from pituitary LH content. It can also be concluded that the absolute value of the blood LRH concentration can not be the sole determining factor of LH secretion.

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