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T R Koiter

Publications and source records attributed to T R Koiter.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effect of in vivo pre-treatment with oestradiol and either GnRH, GnRH agonistic analog or GnRH antagonistic analog on GnRH-stimulated secretion of LH in vitro.

In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH. This augmenting effect of oestradiol became smaller with increasing rates of in vivo administration of GnRH or AG, but not with ANT. With respect to both depletion of the LH stores and suppression of the augmenting effect of oestradiol, AG ist about 20 times as potent as GnRH.

Animals↗
PubMed1991

Effects of luteolysis during late pregnancy on pituitary responsiveness to gonadotrophin-releasing hormone in the rat.

We investigated whether the increase in the gonadotrophin response to gonadotrophin-releasing hormone (GnRH) during the last days of pregnancy and the occurrence of parturition on day 22 of pregnancy in rats are due to the increase in the plasma concentrations of oestradiol-17 beta after luteolysis, which occurs around day 20. In a first series of experiments we studied the effects of s.c. implantation of two capsules containing oestradiol on basal and GnRH-stimulated secretion of LH and FSH before and after luteolysis. Before luteolysis, ovariectomy increased basal LH and FSH; oestradiol treatment prevented this increase partly (FSH) or completely (LH). Ovariectomy also lowered the LH response to the infusion of GnRH (100 ng/h). Oestradiol treatment on the other hand, increased the LH and FSH responses of both intact and ovariectomized rats above the level in intact non-treated control rats. After luteolysis, ovariectomy increased basal FSH only. Treatment with oestradiol did not prevent the increase in basal FSH and ovariectomy diminished the LH response to GnRH infusion. Oestradiol treatment maintained the LH response in ovariectomized rats at the control level and increased the FSH responses of both intact and ovariectomized rats to a higher level than in control rats. Furthermore, the LH and FSH responses of the oestradiol-treated groups of intact and ovariectomized rats were higher after luteolysis than before. In a second series of experiments two capsules containing progesterone were s.c. implanted before or after luteolysis. Progesterone treatment suppressed the plasma concentration of oestradiol and the gonadotrophin responses to infusion of GnRH on the expected day of parturition in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Differential effect of estrogen on pituitary responsiveness to GnRH in women with different forms of hypothalamic amenorrhea.

The effect of treatment with estradiol valerate (6 days, 2-6 mg/day) on basal levels of LH and FSH and on response of LH and FSH levels to GnRH challenge (2 X 25 micrograms GnRH, iv) were investigated in women with "hypothalamic amenorrhea", but without other endocrine disorders. Three groups were studied: 11 women with primary amenorrhea, 10 women exhibiting secondary amenorrhea related with weight loss, and 7 women with normal weight and with amenorrhea persisting after a period of severe weight loss. Before treatment with estradiol valerate the estradiol concentrations in all women were at the lower limit of the follicular phase of a normal ovulatory cycle. In addition, there were no differences between the groups in basal LH and FSH levels and in responses to GnRH challenges. Treatment with estradiol valerate suppressed the basal levels of FSH but not of LH in all women. Estradiol did not affect the response to GnRH challenge in women with primary amenorrhea, weakly augmented the response in women with secondary amenorrhea associated with weight loss, and strongly increased the response in secondary amenorrheic women who had regained normal weight. The results are interpreted in the light of the well-established fact that estrogen augments the gonadotropin response only if the pituitary gland is not exposed to high concentrations of GnRH. It is hypothesized that the differential response to GnRH of the present patients after estrogen treatment reflects differences in GnRH exposure of the pituitary gland, with patients with primary amenorrhea having the highest level of GnRH exposure.

Adult↗
PubMed1989

Glucose and insulin responses during mixed meals or infusion of glucose in pregnant and lactating rats.

We studied the glucose tolerance in freely moving rats throughout pregnancy and lactation and during the first week after weaning. Dioestrous virgin rats served as controls. Basal glucose and insulin levels were determined after a 2-hr fasting period. Subsequently, the changes of the insulin and the glucose levels were determined during ingestion of a mixed ad lib meal or a 2 g mixed test meal, or during infusion of glucose (7.4 mg/min for 20 min) into the vena cava. Basal glucose levels were high during early pregnancy, low during late pregnancy, and in the normal range throughout lactation and after weaning. Basal insulin levels were decreased at the end of lactation. The results of the ad lib meal and test meal experiments were essentially the same. Glucose tolerance during meals was somewhat decreased early in pregnancy. The corresponding insulin responses greatly increased during the last week of pregnancy. Glucose tolerance during IV infusion of glucose was normal during pregnancy, but increased during lactation. Insulin responses to the infusion were increased during pregnancy and decreased during lactation. We concluded that glucose tolerance is hardly affected by pregnancy and even increases in the course of lactation. This is effected by an increased responsiveness of the B-cells to glucose during late pregnancy and by an increased turnover of glucose during lactation. We discuss to what extent the actions of progesterone, placental lactogen and prolactin may explain these adaptions of maternal metabolism.

Animals↗
PubMed1989

Interdependence of oestradiol and 5 alpha-dihydrotestosterone in modulating LH and FSH secretion in rats.

The effects of oestradiol, 5 alpha-dihydrotestosterone (DHT) and oestradiol plus DHT on pituitary responsiveness to LHRH were studied. Rats ovariectomized for 2 weeks were infused s.c. (by osmotic minipump) with LHRH at 250 ng/h for 6 days. Control rats received a sham s.c. pump. On day 3, silicone elastomer implants containing oestradiol or DHT were implanted s.c. and on day 6 the effects of these in-vivo treatments on pituitary LH and FSH content and on in-vitro (perifusion) LH and FSH secretion following maximal LHRH stimulation (1 microgram/ml perifusion medium) were assessed. Luteinizing hormone-releasing hormone alone decreased pituitary LH/FSH content and, in response to acute LHRH challenge in vitro, the absolute rate of LH/FSH release, but not LH/FSH release expressed as a fraction of pituitary content. Oestradiol alone increased pituitary LH/FSH content and LHRH-induced LH/FSH release in vitro, both absolutely and as a fraction of pituitary LH/FSH. Oestradiol exacerbated the decrease in pituitary LH/FSH caused by LHRH pretreatment in vivo, and decreased the absolute rate of LHRH-stimulated LH/FSH release in vitro, but increased this rate when it was expressed as a fraction of pituitary LH/FSH. In both LHRH-treated and control rats, DHT increased pituitary LH/FSH content, did not change the absolute rate of LH/FSH release in response to acute LHRH challenge in vitro, but decreased the rate of LH/FSH release expressed as a fraction of pituitary LH/FSH content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Experimental endotoxemia in pregnancy: in situ glomerular microthrombus formation associated with impaired glomerular adenosine diphosphatase activity.

The mechanism of increased sensitivity for endotoxin in pregnancy as reflected by the formation of microthrombi in renal glomeruli is unknown. It has been shown that reduced glomerular diphosphatase (ADPase) activity in the rat kidney greatly increases the intraglomerular thrombotic tendency. We now studied experimental intraglomerular thrombosis ex vivo in association with glomerular ADPase activity in pregnant and nonpregnant control rats after infusion of either endotoxin or saline solution. Each animal (Wistar rat) was equipped with a permanent vena jugularis catheter and received either endotoxin (1.0 micrograms/kg body weight) (n = 6) or saline solution (n = 5) 7 days before being killed; nonpregnant rats were also treated with endotoxin (n = 5) or saline solution (n = 4). On day 21, before the animals were to be killed, they were anesthetized and their left kidneys were perfused with adenosine diphosphate solution (10 micrograms/ml) and platelet-rich plasma (1 x 10(9) cells/ml). Perfused kidneys were processed for light microscopy, electron microscopy, enzyme cytochemistry at the ultrastructural level, and immunohistology. The results showed decreased ADPase activity exclusively in the glomerular basement membrane of kidneys of pregnant rats treated with endotoxin in contrast to the findings in control rats. In addition, exclusively in the group of endotoxin-treated pregnant rats, significantly increased intraglomerular platelet aggregation could be detected after alternate perfusion ex vivo. We suggest that, in the present model, enhanced susceptibility of glomerular ADPase for endotoxin is due to pregnancy-associated factors that have yet to be identified. This increased susceptibility may promote in situ formation of intraglomerular microthrombi.

Animals↗
PubMed1988

Suppression by LH-releasing hormone (LHRH) of the augmenting effect of estradiol on the secretion of LH and FSH by the rat pituitary gland.

Estradiol sensitizes the pituitary gland for the gonadotropin-releasing activity of LHRH. LHRH desensitizes the pituitary gland and does so in a dose-dependent manner. Moreover, LHRH dose-dependently suppresses the sensitizing effect of EB. In rats with an LHRH concentration in the plasma of about 90 pg/ml, the sensitizing effect of estradiol is absent.

Animals↗
PubMed1988

Commercially available analogues of GnRH and LH secretion.

Six agonistic derivatives of GnRH, four of which have already been evaluated in clinical trials, were compared with GnRH itself in an in vitro test system (incubation of rat pituitary glands). It was investigated 1) how the release of LH was affected when the pituitary glands were incubated in the presence of these analogues or GnRH, and 2) how the release of LH continued after removal of the analogues or GnRH from the medium. It was also investigated how an in vivo pretreatment for 6 days with several doses of 5 of these analogues or GnRH affects 3) the plasma concentration of LH, 4) the pituitary content of LH, and, in vitro, 5) the autonomous and 6) agonist-stimulated secretion of LH. Each of the analogues showed for each of the six investigated parameters a 10- to 100-fold higher potency than GnRH itself. Between the six analogues there were only minor differences. It is discussed how the six investigated parameters may be the expression of one single property of all these analogues, namely a long retention in the pituitary gland with a strong binding to the GnRH receptor.

Animals↗
PubMed1988

Effect of estradiol on the secretion of LH in the GnRH-pretreated rat after treatment with the GnRH-antagonist, Org 30093.

LH responses induced in the long-term ovariectomized rat by GnRH or GnRH agonistic analogue are augmented by E2. The augmentation by E2 does not occur during, but after termination of GnRH pretreatment. In this study it was investigated whether the augmenting effect of E2 develops also in the GnRH-pretreated rat when the animals were treated with GnRH antagonistic analogue. Two weeks after ovariectomy rats were treated for 10 days with 250 ng GnRH/h (GnRH-rats), released by sc implanted osmotic minipumps. Control rats received a Silastic 'sham pump'. Rats were simultaneously treated with solvent (oil) or estradiol benzoate (EB, 3 micrograms, sc). Each group of rats was divided into two subgroups, one receiving solvent, the other the GnRH antagonist, Org 30093 (ANT, 100 micrograms/injection) on 3 consecutive days. In Experiment 1, the pituitary LH content and the LH secretion following stimulation with the agonistic GnRH analogue buserelin, were measured, in Experiment 2, the plasma concentrations of LH before and after cessation of ANT treatment. The effects of treatment with GnRH, EB and ANT were studied on the basis of 1) the height of the maximal LH response and 2) the half-maximally effective dose (ED50) of buserelin. Experiment 1 revealed that GnRH depleted the pituitary gland to about 42% of its original LH content. In EB-treated GnRH-rats the depletion was even stronger (to 14%). After ANT treatment, the pituitary glands of the GnRH-rats were (partly) repleted (oil: to 65%; EB: to 31%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Decidua and the control of corpus luteum function, follicular development and pituitary LHRH-responsiveness in pseudopregnant and pregnant rats.

The mid-pregnancy rescue of corpora lutea can be mimicked in the pseudopregnant rat by induction of decidual tissue in the uterus: in such rats, around day 10, there is neither luteolysis, nor resumption of follicle-development or increase of the pituitary responsiveness to LHRH. The results suggest that the mid-pregnancy rescue of corpora lutea is caused by a maternal factor.

20-alpha-Dihydroprogesterone↗
PubMed1987

Suppression by LRH of the stimulatory effect of oestradiol on the secretion of LH by the rat pituitary gland.

Ovariectomized rats were infused with varying doses of luteinizing hormone-releasing-hormone (LRH). Some of the rats were also treated with oestradiol benzoate (EB). The effects of these pre-treatments on the in vitro release of luteinizing hormone (LH) were studied. The following parameters of in vitro LH release were measured: the autonomous secretion rate; the secretion rate following maximum stimulation with LRH, and the total quantity of LH released during the 6-hour experiment. The in vivo pre-treatments with LRH and EB dose-dependently decreased the pituitary LH content as well as all three of the above parameters of in vitro LH secretion. There was a linear relationship between the pituitary LH content and the three parameters of in vitro LH release. These parameters were therefore expressed as percentage of the pituitary LH content to give the relative LH secretion rates. The three parameters were thereby corrected for LRH/EB-induced changes in the pituitary LH content. In this way we obtained information on the effects of LRH and EB on the state of the LH release mechanisms of the gonadotropes. EB potentiated the LRH-induced depletion of the pituitary LH stores at all in vivo LRH infusion rates. The effect of EB on the quantity of LH released during perifusion in vitro, however, varied with the previous LRH infusion rates. After LRH infusion rates lower than about 120 ng/h (which establishes plasma concentrations of about 70 ng/l) EB enhanced the stimulated quantity of LH released. After higher rates of LRH infusion, EB lowered the amount of LH released.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Minor interference of low-dose pulses of GnRH with the positive effect of oestradiol on the pituitary gland.

In the ovariectomized rat we investigated the effects of prolonged treatment with oestradiol and 'physiological' pulses of exogenous GnRH on the GnRH-responsiveness of the pituitary gland. Rats were for 20 h pre-treated with either GnRH (3-ng pulses of 3 min duration every 20 min) or saline and for 19 h with either oestradiolbenzoate (OB; 3 micrograms/sc injection) or oil. Then LH and FSH responses were evoked by continuous test infusions of GnRH at the rates of either 60, 100, 150 or 1000 ng/h, lasting 10 h. It appeared that, irrespective of pre-treatment with either GnRH or saline, OB caused an increase of the maximal LH and FSH responses (that is the responses to the maximal stimulus of 1000 ng GnRH/h), and an increase of the GnRH-sensitivity of the pituitary gland, as far as the FSH secretion is concerned. GnRH pulses caused, irrespective of pre-treatment with OB or oil, a decrease of the GnRH-sensitivity of the pituitary gland, as well as a decrease of the maximal FSH response and of the pituitary FSH content. It was concluded that low-dose pulses of exogenous GnRH desensitize the pituitary gland and deplete the pituitary FSH stores, but do not change the positive effect of oestradiol on the maximal gonadotropin response.

Animals↗
PubMed1987

Pituitary responsiveness to LHRH during pregnancy in the rat: effect of progesterone.

The LH and FSH responses to a standard infusion of LHRH were studied on days 8, 12, 15, 17, 19, 21 and 22 after conception as well as on day 23, i.e. after parturition. Groups of rats were also killed on days 8, 15, 19, 22 and 23 and on the day of pro-oestrus of the 4-day cycle for the assay of progesterone, 20 alpha-dihydroprogesterone (DHP), oestradiol-17 beta, LH and FSH. Finally, the post-partum surges of LH and FSH were compared with those at pro-oestrus in 4-day cyclic rats. The LH and FSH responses to LHRH were relatively low on days 8 and 12, twice as high on days 15, 17 and 19, had increased further on day 21 and reached maximal values on day 22. The gonadotrophin responses were low on day 23. The post-partum surges of LH and FSH were much higher than the pro-oestrous surges. Pituitary contents of LH and FSH were higher than on pro-oestrus of the 4-day cycle. On day 23, however, the pituitary contents had declined by 60-80%. No apparent relationship was found between plasma concentrations of LH and FSH and LHRH responsiveness during pregnancy. Concentrations of oestradiol-17 beta on day 22 were higher than on all other days of pregnancy, but lower than on pro-oestrus of the 4-day cycle. Concentrations of progesterone were high until day 19 and low on days 22 and 23; the concentration of DHP was low until day 19 and very high on days 22 and 23.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Plasma gonadotrophin concentrations, pituitary gonadotrophin content and pituitary responsiveness to LHRH in rats treated with LHRH and oestradiol benzoate.

Suppression of gonadotrophin secretion during prolonged treatment with a high dose of LHRH was studied. Long-term ovariectomized rats were infused for 6 days with various doses of LHRH (25, 50, 100, 250 or 500 ng/h) with or without simultaneous treatment with oestradiol benzoate (OB; 3 micrograms/s.c. injection); a further group was treated with OB only. The effects of these treatments were studied on plasma concentrations of LH and FSH, the pituitary content of LH and FSH and on LH and FSH secretion in vitro (perifusion) in the unstimulated state and following maximal LHRH stimulation (1 microgram LHRH/ml perifusion medium). Administration of LHRH caused a dose-dependent reduction in plasma concentrations of LH and FSH and depleted the pituitary LH/FSH stores. Treatment with OB lowered the plasma concentration of LH to about 30% and that of FSH to about 65% of the control values. Administration of OB plus a low dose of LHRH (25 or 50 ng/h) markedly stimulated the secretion of LH but not of FSH, so that the plasma concentrations of LH were fully restored to the control value. With higher rates of LHRH infusion, OB caused no enhancement of the plasma concentrations of LH and FSH. The experiments in vitro revealed a sensitizing, i.e. stimulatory effect, of OB on LHRH-stimulated LH and FSH secretion. However, the higher the rate of infusion of LHRH the smaller the sensitizing effect. Interpolation from dose-response curves showed that an LHRH infusion rate of about 150 ng/h (which would establish a plasma concentration of LHRH of about 68 pmol/l) would have no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The prolonged action of the LHRH agonist buserelin (HOE 766) may be due to prolonged binding to the LHRH receptor.

Hemi-pituitary glands of ovariectomized rats were superfused for 4 h with either LHRH or the analog buserelin (HOE 766) at several concentrations, and thereafter with medium only for another 1.5 h. In a further experiment glands were exposed for 2.5 h to LHRH or buserelin at a single concentration (5 ng/ml) and subsequently for another 2.5 h to either the same agonist (LHRH or buserelin) alone (5 ng/ml), the agonist plus an LHRH-antagonist (ORG 30093, 1000 ng/ml), the LHRH- antagonist alone, or medium alone. LHRH and buserelin stimulated gonadotropin release equally well. After cessation of this stimulation, the gonadotropin release by the buserelin-treated pituitary glands and the glands, treated with the highest dose of LHRH (1000 ng/ml), continued, while the release by the glands, treated with the lower doses of LHRH, declined. The LHRH-antagonist completely blocked the release of LH, stimulated by buserelin or LHRH, as well as the prolonged activation of the release, caused by buserelin pre-treatment. In a superfusion experiment with pituitary cell aggregates of 14-day-old intact female rats, buserelin stimulated the release of LH much more effectively than LHRH itself. Moreover, the release caused by buserelin declined more slowly after cessation of the stimulation. Finally, in a pituitary cell monolayer culture the Kd's of LHRH, buserelin and the antagonist were determined as 4.7 X 10(-9) M, 2.4 X 10(-10) M and 4.6 X 10(-9) respectively. It was concluded that the estimates of the potencies of LHRH and buserelin depend on the choice of the test-system. It is suggested that the long duration of action of buserelin is at least partly due to prolonged binding to the LHRH-receptor.

Animals↗
PubMed1986

Comparison of the time courses of luteinizing hormone (LH) secretion rates during continuous stimulation by LH-releasing hormone (LH-RH) in vivo and in vitro.

The patterns of LH secretion during constant stimulation of the pituitary glands of estradiol-treated ovariectomized rats with a maximally stimulating amount of LH-RH in vivo and in vitro correspond with each other qualitatively and quantitatively. In vitro the changes with time of the LH secretion rate are somewhat retarded, especially the occurrence of desensitization.

Animals↗
PubMed1986

Effect of clomiphene citrate on the in vitro release of LH and FSH by the pituitary gland of the long-term ovariectomized rat pretreated with LRH or with LRH and oestradiol benzoate.

The effect of a combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and either oestradiol benzoate (OB), clomiphene (-citrate) or OB plus clomiphene on the autonomous and the supramaximally LRH-stimulated in vitro secretion of LH and FSH by pituitary glands of long-term ovariectomized (OVX) rats was studied using a hemipituitary perifusion system. The concentration of LRH in the perifusion medium was 1 microgram/ml. Pre-treatment with LRH during 5 days was effected by means of sc implanted Alzet osmotic minipumps; control rats received a piece of silastic with the dimensions of a minipump. OB, 3 micrograms/injection, clomiphene 100 micrograms/injection or solvent were given on days 2 and 4 (day of perifusion: day 5). In rats not pre-treated with LRH neither OB, nor clomiphene changed the content of the pituitary gonadotropin stores. There was only a small but significant positive effect of the combined treatment with OB and clomiphene on the pituitary FSH content. LRH (partly) depleted the gonadotropin stores. This effect of LRH was potentiated by OB, but not by clomiphene. Clomiphene prevented the depletion-potentiating effect of OB. OB raised the LRH-stimulated secretion of LH and FSH as well as the autonomous secretion of LH. Clomiphene raised the LRH-stimulated (not the autonomous) secretion of LH and FSH. OB plus clomiphene had the same effect as OB alone. Clomiphene also raised the LRH-stimulated secretion of LH and FSH after pre-treatment with LRH, but OB did not do so: LRH prevented the stimulatory effect of OB but not of clomiphene. OB plus clomiphene had the same effect as OB alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗