On the dynamics between gonadotrophin surge-inhibiting factor and gonadotrophin releasing hormone (GnRH): role of self-priming and desensitization in the luteinizing hormone response to GnRH after follicle stimulating hormone treatment

The effects were studied of follicle stimulating hormone (FSH)-induced production of gonadotrophin surge-inhibiting factor (GnSIF) on three phases of the pituitary responsiveness to gonadotrophin releasing hormone (GnRH): the unprimed, primed and desensitized phases. Rats were injected with FSH on two occasions during the oestrous cycle. Spontaneous luteinizing hormone (LH) surges were measured as well as GnRH-induced LH surges on the day of pro-oestrus during infusions with 100-4000 pmol GnRH/rat/10 h, in phenobarbital blocked rats. The spontaneous LH surges were attenuated or completely inhibited by the FSH treatment. FSH suppresses and prolongs the unprimed LH response and delays GnRH self-priming, especially during infusions with low concentrations of GnRH. This treatment does not affect the total LH response (area under curve) to the highest concentrations of GnRH and after ovariectomy. On the other hand, this response is suppressed during infusions with the lower concentrations of GnRH. Hence, FSH, via GnSIF, delays maximal priming of the LH response to GnRH, whereas the suppression of LH release is a consequence of the GnRH-induced progressed state of desensitization. The inconsistent effects of FSH on the mid-cycle LH surges are explained as a result of the interaction between the relative strengths of GnRH and GnSIF.     

Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF)

Although most studies have indicated that Ber-EP4 immunostaining can assist in differentiating epithelial pleural mesotheliomas from adenocarcinomas that metastasize to the pleura, the percentage of positive cases has varied greatly among different studies. Authors of a recent publication concluded that Ber-EP4 has no diagnostic utility in separating these conditions. To determine whether Ber-EP4 has any value in distinguishing mesothelioma from adenocarcinoma, 70 formalin-fixed epithelial pleural mesotheliomas, 20 pulmonary adenocarcinomas, 59 nonpulmonary adenocarcinomas, 4 squamous cell carcinomas of the lung, 6 transitional cell carcinomas, and 31 adenocarcinomas of unknown origin that metastasized to the pleura were stained with this antibody. Reactivity was observed in 18 (26%) of 70 mesotheliomas and in all 20 (100%) of the pulmonary adenocarcinomas, in 55 (93%) of the 59 nonpulmonary adenocarcinomas, in 4 (100%) of 4 squamous cell carcinomas of the lung, in 4 (67%) of 6 transitional cell carcinomas, and in 26 (84%) of 31 adenocarcinomas of unknown origin that metastasized to the pleura. The staining in the mesotheliomas was focal and restricted to a limited number of cells, in contrast with staining in the pulmonary adenocarcinomas in which it was invariably diffuse. The extent of the staining in the nonpulmonary adenocarcinomas and the metastatic adenocarcinomas of unknown origin was less consistent--negative or focal in some cases and diffuse in others. Therefore, while Ber-EP4 seems to be helpful in separating epithelial pleural mesotheliomas from lung adenocarcinomas, its value in distinguishing mesotheliomas from other tumors metastatic to the pleura is more limited and depends largely on the site of origin of the metastatic tumor.     

Changes in gonadotrophin response to gonadotrophin releasing hormone in normal women following bilateral ovariectomy

OBJECTIVE: Pituitary responsiveness to GnRH varies throughout the normal menstrual cycle. We have investigated whether there are differences in the ovarian mechanisms which regulate gonadotrophin secretion between the follicular and the luteal phase of the cycle. DESIGN: Normally ovulating women were studied during the first week following hysterectomy plus bilateral ovariectomy performed either in the mid- to late follicular phase (follicle size 16 mm) or in the early to midluteal phase (5 days post LH peak). The response of LH to a single dose of 10 micrograms GnRH was investigated 2 hours before the operation and every 12 hours after the operation until postoperative day 4 and every 24 hours until day 8. PATIENTS: Fourteen normally cycling premenopausal women with normal FSH (< 10 IU/l). Seven women were ovariectomized in the follicular and 7 in the luteal phase. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in FSH (delta FSH) and LH (delta LH) at 30 minutes above the basal value. RESULTS: Basal levels of FSH and LH before the operation were significantly lower in the luteal than the follicular phase (P < 0.05), while those of oestradiol (E2) were similar. Also, similar were delta LH and delta FSH values. Serum progesterone and immunoreactive inhibin (Ir-inhibin) concentrations before the operation were higher in the luteal than the follicular phase (P < 0.05). Following the operation, serum E2, progesterone and Ir-inhibin values declined dramatically, while basal FSH and LH as well as delta FSH values showed a gradual and significant increase. The percentage increase in FSH and LH values (mean +/- SEM) on day 8 after the operation was similar in the follicular (453 +/- 99% and 118 +/- 35% respectively) and the luteal phase (480 +/- 71% and 192 +/- 45% respectively). In contrast to delta FSH, delta LH values after a temporal increase 12 hours from the operation, remained stable in the follicular phase and declined significantly in the luteal phase up to day 4. CONCLUSIONS: Basal gonadotrophin secretion during the normal menstrual cycle is predominantly under a negative ovarian effect. It is suggested that in contrast to FSH, the secretion of LH in response to GnRH is controlled by different ovarian mechanisms during the two phases of the menstrual cycle.     

Effect of acute corticotropin releasing factor on pituitary-adrenocortical responsiveness in elderly women and men

Aging is related to critical changes of the hypothalamo-pituitary-adrenal function. A decline in serum DHEA levels has been demonstrated in healthy elderly subjects, while ACTH and cortisol concentrations remain at normal values. The purpose of the present study was to investigate the effect of aging on pituitary-adrenal responsiveness to hCRF in subjects of both sexes. A group of 12 physically and mentally healthy elderly subjects and a group of 12 young controls of both sexes have been selected. Blood samples were collected before and after i.v. bolus injection of hCRF; ACTH, cortisol and DHEA levels were then determined by RIA. Basal ACTH and cortisol levels did not result statistically different between controls and elderly subjects, while DHEA showed a clear and significant age-related decrease (p < 0.01). Following the hCRF injection, the responses of ACTH, cortisol and DHEA in aged subjects were higher than in young controls; ACTH (p < 0.03) and cortisol (p < 0.01) were higher in aged women than in men. The present study demonstrated that aging is associated with an increased responsiveness of ACTH, cortisol and DHEA to exogenous hCRF supply. A hyperactivation of the pituitary-adrenal secretory activity may explain the age-related of the same axis. Gender probably has a significant influence on basal and stimulated hormonal secretion. In conclusion, hCRF test may become a useful clinical tool in establishing a neuroendocrine correlation with central disturbances associated to aging.     

Sterilization during puerperium (author's transl)

Sterilization of the woman during puerperium is performed immediately following delivery via a periumbilical incision during a caesaren section isthmica intraperitonealis via laparoscopy or 3--5 days following delivery by pelviscopy. The surgical procedure currently in use for ligating or severing the fallopian tubes is accompanied by extensive loss of blood. This procedure should, therefore, be replaced by the coagulation method which is safer and does not contribute to the formation of adhesions. If the abdomen has been dissected, either high frequency current or the Endo-coagulation procedure may be used to produce the destructive heat necessary to coagulate the fallopian tubes. If the abdomen has not been opened and the coagulation of the fallopian tubes must be performed via pelviscopy, the Endo-coagulation method should be used instead of the high frequency current procedure which cannot be absolutely controlled by the surgeon. The Endo-coagulation procedure works at or about the temperature of boiling water. The failure rate for this procedure is about 2--3 %0.     

Regulation of hippocampal gonadotropin releasing hormone (GnRH) receptor mRNA and GnRH-stimulated inositol phosphate production by gonadal steroid hormones

Cooperation in the action of agonists suggests that there are multiple binding sites on 5-hydroxytryptamine3 (5-HT3) receptors. The purpose of this study was to characterize these binding sites and their interactions on both native and cloned 5-HT3 receptors. The affinities of competitive 5-HT3 receptor antagonists were similar regardless of whether the receptors were labeled with [3H]RS-42358, [3H]granisetron, or 1-(m-[3H]chlorophenyl)biguanide ([3H]mCPG). By contrast, the affinities of the agonists 5-HT, mCPG, and phenylbiguanide were approximately 10-fold higher when the receptors were labeled with [3H]mCPG. The dissociation of [3H]mCPG, [3H]RS-42358, and [3H]RS-25259, but not [3H]granisetron, from both cloned and native 5-HT3 receptors was markedly slower in the presence of 5-HT or 2-methyl-5-HT than in the presence of antagonists such as RS-42358. This suggests that the binding of these agonists to unoccupied sites on the receptor can increase the receptor's affinity for prebound ligands and thereby slow their dissociation. These data support previous indications of positive cooperation among multiple binding sites on both native and cloned 5-HT3 receptors, and they extend this idea by demonstrating that agonists can modify the interaction of some, but not all, antagonists with the receptor.     

Gonadotropin response to synthetic gonadotropin hormone-releasing hormone (GnRH) in chronic schizophrenia

GnRH stimulation tests were performed in 15 adult male chronic hebephrenic schizophrenics and 15 oligophrenic controls, matched for age and length of hospitalization. GnRH was given at doses of 50, 100 and 150 gamma to five subjects of each type, and FSH and LH levels in the blood were assayed at 0, 10, 20, 30, 60, and 90 minutes. The tests were performed twice in schizophrenics off therapy and after 10, 20 and 30 days of chlorpromazine therapy (4 mg/kg body weight/day, per os). The controls were not given chlorpromazine and were tested only twice. Schizophrenics showed relative increases in both FSH and LH which were greater than those of the controls, and the response persisted longer. Chlorpromazine had no effect on the test.     

Pretreatment with somatostatin analog SMS 201-995 potentiates growth hormone (GH) responsiveness to GH-releasing factor in short children

Previous studies in children have shown inconsistent, poorly reproducible GH responses to exogenous GH-releasing factor (GRF), with wide individual variability. In the present study, we tested the hypothesis that prior administration of the long-acting somatostatin analog, SMS 201-995 (SMS), will enhance GH responsiveness to a subsequent GRF challenge. Two study protocols were employed in 37 children with short stature [M = 31, F = 6, ages 11.8 +/- 1.6 yr (mean +/- SEM), height -2.25 +/- 0.55 SDS (SD scores)]. In both studies, each subject served as his/her own control. In the first study, which was designed to determine optimal SMS dose and regimen, SMS, in doses ranging from 0.8-2.2 micrograms/kg sc, was randomly administered or omitted at 0800 h after an overnight fast, and a GRF bolus (50 micrograms, iv) was given 4 h later. In the second study, we employed a protocol identical to study 1 except for the use of standard doses of SMS (1 microgram/kg, sc) and GRF (1 microgram/kg, iv) and an additional 1-h delay of the GRF injection. Plasma GH levels were measured every 20 min from 0800 h until 2 h after the GRF injection in both studies. In study 1 (n = 12; M = 10, F = 2), SMS significantly suppressed spontaneous GH secretion (expressed as the mean +/- SEM GH AUC during the 4-h SMS-GRF interval, AUC 1:2.2 +/- 0.4 vs. 6.2 +/- 0.9 micrograms/L.h; P < 0.001), GH responsiveness to GRF (GH AUC during the 2 h after the GRF injection, AUC 2: 41.5 +/- 7.8 vs. 85.0 +/- 13.5 micrograms/L.h; P < 0.001), and the GH peak response (17.4 +/- 3.1 vs. 36.0 +/- 6.2 micrograms/L; P < 0.001), compared to control tests. In contrast, in study 2 (n = 25; M = 21, F = 4), whereas spontaneous GH secretion was still suppressed during the 5-h SMS-GRF interval (AUC 1:3.8 +/- 0.4 vs. 7.4 +/- 1.1 micrograms/L.h; P < 0.001), both the GH peak response (56.7 +/- 5.5 vs. 30.5 +/- 3.0 micrograms/L; P < 0.0001) and the GH AUC (AUC 2: 103.7 +/- 10.3 vs. 77.5 +/- 6.8 micrograms/L.h; P < 0.05) after GRF administration were significantly augmented by pretreatment with SMS, compared to control tests. Taken together, these results indicate that a priming SMS dose of 1 microgram/kg has a significant permissive effect on GH responsiveness to exogenous GRF administered 5 h later.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of gonadotrophin releasing hormone and follicle stimulating hormone in conjunction with pregnant mare serum gonadotrophin on the superovulatory response in crossbred sheep in India

The effectiveness of triple-marker testing as screening for Down syndrome needs to be evaluated by means of formal meta-analytic techniques. We did a MEDLINE search to identify studies evaluating the detection of Down syndrome by use of the triple-marker test. Reference lists of articles were also checked. Papers published in either English, French, or German from 1966 to November 1996 were eligible for this review. Twenty cohort studies were identified. Results of sensitivities and false-positive rates from different subgroups of the study sample were compared by using summary receiver-operating characteristic curve analysis. Medians of sensitivities and false-positive rates were also estimated. A total of 194,326 patients were included. In women of all ages, the medians for sensitivities were 67, 71, and 73 percent when the cutoffs used were 1:190-200, 1:250-295, and 1:350-380, respectively. The median false-positive rates fluctuated between 4 and 8 percent. For women at or above 35 years old, the medians of sensitivity and false-positive rate were 89 and 25 percent, respectively, when the chosen cutoff was 1:190-200. In patients below 35 years old, the median sensitivity was 57 percent if the cutoff used was 1:250-295. Summary receiver-operating characteristic curves showed that 1:190 was the best cutoff for predicting Down syndrome. The triple-marker testing is an effective screening method of detecting Down syndrome pregnancies. It is less effective in younger than in older age groups and may be offered as an alternative to amniocentesis to pregnant women over 35.     

Impairment of growth hormone responsiveness to growth hormone releasing hormone and pyridostigmine in patients affected by Prader-Labhardt-Willi syndrome

In order to evaluate the impairment of GH response in patients affected by Prader-Labhardt-Willi (PLW) syndrome, in 18 patients we studied GH response to clonidine and to GHRH + pyridostigmine, a cholinergic drug which enhances GHRH induced GH responsiveness in obese patients. After clonidine GH response was abnormal in 14/18 subjects (mean GH peak: 4.1 +/- 1.3 micrograms/l; area under curve: 208.1 +/- 74.2 micrograms/l.h) while all but 5 patients showed an inadequate GH response to GHRH + pyridostigmine (mean GH peak: 13.4 +/- 2.5 micrograms/l; area under curve: 903.4 +/- 171.0 micrograms/l.h). However, in the three patients with low adiposity index, GH response to GHRH + pyridostigmine was significantly higher than that observed in fatter subjects. In addition, GH response to GHRH + pyridostigmine was negatively correlated to age and adiposity index. In conclusion, our data are consistent with the hypothesis of the existence of a complex derangement of GH neuroendocrine regulation in these subjects.     

Stress-induced sleep deprivation modifies corticotropin releasing factor (CRF) levels and CRF binding in rat brain and pituitary

OBJECTIVE: Mast cells are suggested to play an essential role during development of varices in the lower limbs. EXPERIMENTAL DESIGN: Investigation of the ultrastructure of mast cells in varicose lesions. SETTING: Saga Medical School, Yamamoto Surgical Hospital. PATIENTS: Eighteen varicose veins of 17 patients and 9 normal saphenous veins of 9 patients were examined. Patients who had undergone sclerotherapy for varices were excluded. INTERVENTIONS: Radical stripping surgery was performed on all varicose veins. MEASURES: Ultrastructural observations. RESULTS: In normal saphenous veins, mast cells usually singly embedded in dense collagen bundles as resident cells. They have characteristic crystalline granules of storage type. In varicose veins, mast cells show different features such as an increase of altered granules of discharging type, degranulation and intimate relationship with fibroblasts and lymphocytes. CONCLUSIONS: The observations suggest the presence of mast cell-mediated mechanism by releasing some mediators in the development of varices.     

Gonadotropin-releasing hormone (GnRH) in ancient teleosts, the bonytongue fishes: putative origin of salmon GnRH

PURPOSE: To measure the compressive forces of the haptics of 28 intraocular lens (IOL) models for different modes of compression and compare the results of two types of measurements. SETTING: Department of Ophthalmology, Central Hospital of Central Finland, Jyv?skyl?, Finland. METHODS: The haptics of 28 types of IOLs were compressed to a diameter of 9.0 mm between curved anvils. The compression forces in the plane of compression (i.e., in the plane of the optics) were measured at 0.5 mm intervals. During compression, the optics and the haptics were free to rotate with respect to the anvils. The results were compared with those of earlier measurements in which the optics were held fixed during compression. Perpendicular forces were measured at 0.4 mm intervals. RESULTS: The measured forces in the plane of the optics varied between 114 and 659 mg at a diameter of 10.0 mm and 192 and 1047 mg at a diameter of 9.0 mm. When compressed to 10.0 mm in diameter, the forces were 1 to 75% lower than when lens rotation was not possible. The forces perpendicular to the optic varied between 0 and 96 mg at a 10.0 mm diameter and correlated with the forces in the plane of the optic. CONCLUSION: The compression forces of the lens haptics were generally lower when the lenses were allowed to rotate during compression. The orders of stiffness of the haptics in these two measurements were similar. The perpendicular forces were generally small and correlated significantly with the forces measured in the plane of the optic.     

Regulation of gonadotropin-releasing hormone (GnRH) receptor gene expression in sheep: interaction of GnRH and estradiol

GnRH and estradiol are important regulators of GnRH receptors. When delivered to the anterior pituitary gland continuously, GnRH decreases numbers of GnRH receptors on gonadotropes. Treatment with estradiol consistently increases numbers of GnRH receptors. Because estradiol acts via intracellular receptors while GnRH exerts its effects through a membrane receptor, it is likely that these hormones influence GnRH receptor expression via different mechanisms. In this experiment, we tested two hypotheses: 1) continuous infusion of GnRH will decrease expression of the GnRH receptor gene; and 2) estradiol will override the negative effects of continuous infusion of GnRH on GnRH receptor expression. Ovariectomized ewes were administered either GnRH (10 microg/h, n = 10) or saline (n = 10) continuously for 136 h. At 124 h, 5 ewes in each group were administered estradiol (25 microg i.m.) and anterior pituitary glands were collected 12 h later. Treatment with GnRH caused an abrupt increase in circulating concentrations of LH, and the maximal mean concentration was observed 4 h after the start of GnRH infusion. Following this increase, concentrations of LH in GnRH-treated ewes declined and were similar to those in saline-treated ewes from 8 h to 124 h. After injection of estradiol at 124 h, circulating concentrations of LH increased in both GnRH- and saline-treated ewes. However, this response occurred within 6 h in ewes treated with GnRH compared with 9 h in ewes treated with saline (P < 0.05). Compared with saline-treated controls, treatment with GnRH decreased mean steady-state amount of GnRH receptor messenger RNA (mRNA) (P < 0.01) and concentration of GnRH receptors (P < 0.05). Treatment with estradiol caused an increase in concentrations of GnRH receptor mRNA (P < 0.05) and GnRH receptors (P < 0.01). Amounts of GnRH receptor mRNA and numbers of GnRH receptors in ewes treated with both GnRH and estradiol were not different from those in the control group but were higher (P < 0.002) relative to ewes treated with GnRH alone. Treatment with GnRH and estradiol also influenced the expression of genes encoding the LHbeta and FSHbeta subunits. Compared with saline-treated controls, treatment with GnRH reduced steady-state amounts of mRNA encoding LHbeta subunit (P < 0.005) and FSHbeta subunit (P < 0.05). Treatment with estradiol caused a decrease in concentrations of FSHbeta subunit mRNA (P < 0.01) but did not affect amounts of LHbeta subunit mRNA. The combined treatment of GnRH and estradiol reduced concentrations of mRNA encoding LHbeta subunit (P < 0.01) and FSHbeta subunit (P < 0.005). From these data we conclude that 1) reduced numbers of GnRH receptors during continuous infusion of GnRH are mediated in part by decreased expression of the GnRH receptor gene; and 2) estradiol is able to override the negative effect of GnRH by stimulating an increase in GnRH receptor gene expression and GnRH receptor concentrations. Therefore, although the gonadotrope becomes refractory to GnRH during homologous desensitization, this desensitization does not affect the cell's ability to respond to estradiol.     

Gonadal hormones and gonadotropin-releasing hormone (GnRH) alter messenger ribonucleic acid levels for GnRH receptors in sheep

GnRH regulates the synthesis and secretion of pituitary gonadotropins. The number of receptors for GnRH (GnRH-rec) can vary from 500 to 15,000-20,000/gonadotrope in ovine pituitary cultures after treatment with physiologically relevant combinations of gonadal hormones. This large range suggests that regulation of GnRH-rec expression may be an important control point in GnRH action at the pituitary level. Reported here are the changes in GnRH-rec mRNA associated with pituitary treatments (48 h) of 17 beta-estradiol (E), progesterone (P), and an enriched preparation of porcine follicular inhibin (IN). Northern blot analysis was used to detect 3 species of GnRH-rec mRNA in primary ovine pituitary culture [5.5 kilobases (kb; 32%), 3.6 kb (51%), and 1.4 kb (17%)]; all were changed in parallel by E, P, and IN. GnRH-rec mRNAs were increased 190% over control levels after treatment with either E or IN, and 400% with E and IN combined; when E and IN were added along with P, the increase was only 50% (P caused an 87% inhibition of E plus IN induction). The addition of P in the absence of any other treatment reduced levels of GnRH-rec mRNA by 50%. Studies were also conducted with GnRH agonists (GnRH-A) due to their widespread clinical use for down-regulating reproductive function in men and women. The addition of GnRH-A to cultures was as effective as P in blocking E plus IN induction of GnRH-rec mRNA. In vivo studies in wethers showed that 7 days of chronic treatment with GnRH-A decreased all sizes of ovine GnRH-rec mRNA by 84-89%. These data indicate that E, P, and IN change GnRH-rec levels at least in part by changing levels of GnRH-rec mRNAs. They also show that GnRH-A can almost entirely block E plus IN induction of GnRH-rec mRNA in vitro and decrease levels of GnRH-rec mRNA in vivo in wethers.     

Ileus due to appendicitis in the puerperium

A report is given in a case of appendicitis after delivery in childbed. This was the third case of appendicitis within 17 657 deliveries in the gestation of the district hospital in Sangerhausen in the period from 1960 to 1975. The chronic relapsed appendicitis produced a paralytic Ileus. By using correspondent measures (infusional therapy, appendectomy, adhesion solutions) the patient could be cured without any complications. The patient feeled a Douglas-touch of pain that extended especially to the right. This was the only symptom that was noticed by the patient besides the Ileus that had been clinical well defined and secured with the help of x-ray photo.     

Decreased hypotensive responsiveness to nitric oxide donor S-nitroso N-acetyl-DL-penicillamine (SNAP) in spontaneously hypertensive (SHR) rats

The nosocomial infection (NI) rate in German hospitals was studied in order to create reference data for comparison in hospitals where ongoing surveillance is impossible. The study was designed as a one-day prevalence study. Patients in 72 selected hospitals (inclusion criteria: acute care hospitals with departments for general medicine, surgery, obstetrics/gynaecology) were examined by four external investigators (physicians trained and validated in the diagnosis of NI). A total of 14,996 patients were studied. The overall prevalence rate was 3.5% (CI 3.1-3.9) with a variation of 0-8.9% between hospitals. The commonest NI were: urinary tract infection (42.1%), lower respiratory tract infection (20.6%), surgical site infections (15.8%) and primary sepsis (8.3%). The highest prevalence rate (15.3%) was found in intensive care ward patients, followed by surgery (3.8%), general medicine (3.0%) and gynaecology/obstetrics (1.4%). The infection rate varied significantly with hospital size. A microbiology laboratory report was only available for 56.5% of patients thought to have an NI, and there were remarkable differences between hospitals with and without an on-site microbiology laboratory. Because of this and other methodological reasons the NI prevalence rates reported here may represent the absolute minimum of nosocomially infected patients in Germany.     

Vascular responsiveness in alloxan-induced diabetes-susceptible (ALS) and resistant (ALR) mice

Changes in reactivity of vascular smooth muscles of male alloxan-induced diabetes-susceptible (ALS) and resistant (ALR) mice aorta were investigated at 2 weeks, 1, 2 and 4 month(s) after the injection of alloxan (45 mg/kg, i.v.). The glucose levels in blood and urine of all the alloxan-treated ALS mice were markedly elevated while those in alloxan-treated ALR and non-treated ALS and ALR mice were not altered. The magnitude of high K+ (65.4 mM)-induced contractions were not affected by the treatment of alloxan. Norepinephrine-induced contractions in vascular smooth muscles of ALS mice in a diabetic state for 2 or 4 months were significantly potentiated. The contractile sensitivity to prostaglandin F2 alpha (PGF2 alpha) was increased in the 4-month-diabetic state. Responsiveness to 5-HT did not vary in the diabetic mouse. Vasorelaxation induced by nitroprusside was attenuated in 2 weeks, 2 or 4 month-diabetic ALS mice. Similarly the inhibitory effects of levcromakalim were attenuated at 2 and 4 months. The influences of diabetes on the inhibitory effects of forskolin or verapamil were very small or not detected. The effects of the vasomodulators used in this study on the vascular smooth muscles of alloxan-treated ALR mice did not differ from those of untreated ALR mice. The results from using ALS and ALR mice suggest that the vasoreactivities to some vasomodulators are changed especially in the long-term diabetic state and that when diabetes was not induced the dose of alloxan does not have any effect on vascular smooth muscle.     

Inhibition of growth and proliferation of EcRG293 cell line expressing high-affinity gonadotropin-releasing hormone (GnRH) receptor under the control of an inducible promoter by GnRH agonist (D-Lys6)GnRH and antagonist (Antide)

The mechanism by which gonadotropin-releasing hormone (GnRH) agonists and antagonists inhibit tumor cell growth and proliferation is controversial. Direct mediation of the antitumor effects through the high-affinity GnRH receptors has been questioned because of the low level of expression of receptors on the tumor cells. We have developed a human kidney embryonic cell line (EcRG293) that expresses high-affinity GnRH receptor under the control of an inducible promoter activated by muristerone A. Treatment of this cell line with either GnRH agonist (D-Lys6)GnRH or GnRH antagonist (Antide) resulted in a significant, time-dependent decrease in cell proliferation in muristerone A-induced cells but not in the uninduced cells, which do not express the GnRH receptor. These data suggest strongly that the antitumor effect of GnRH agonists and antagonist is specific, direct, and mediated through high-affinity GnRH receptors present on the cell membranes of tumor cells.