EFFECT OF THE URINARY INHIBITOR ON THE UTERINE WEIGHT RESPONSE TO GONADOTROPHINS

1968 ◽  
Vol 59 (3) ◽  
pp. 417-425 ◽  
Author(s):  
L. J. Hipkin

ABSTRACT A boiled kaolin acetone extract of urine inhibited the activity of small doses of chorionic gonadotrophin (HCG), pregnant mares' serum gonadotrophin (PMS) and urinary pituitary gonadotrophin in the immature mouse uterus assay. Bigger doses of these gonadotrophins were not affected. The gonadotrophin inhibitory material (GIM) did not affect the uterine weight response to pituitary follicle-stimulating hormone (FSH) or oestrone. It was noted that the gonadotrophin inhibitory effects of GIM were very similar to the reports of inhibition of gonadotrophins in hypophysectomised animals. It was therefore postulated that GIM inhibits the endogenous gonadotrophin secretion which is necessary for the activity of certain gonadotrophins at low doses. In support of this hypothesis it was found that HCG was not inhibited by GIM if the animals were also given FSH. The conclusion that GIM acts by inhibiting endogenous gonadotrophin is contrary to the normally accepted view that GIM inhibits exogenous HCG or luteinising hormone directly.

1970 ◽  
Vol 64 (3) ◽  
pp. 421-430
Author(s):  
L. J. Hipkin

ABSTRACT A urinary extract (GIM), which previously had been shown to inhibit small doses of human chorionic gonadotrophin (HCG) in the mouse uterus assay, was tested in the rat. In this species, GIM caused an increase in the basal uterine weight and potentiated the response to 0.1 IU HCG. Similar results, and in addition augmentation of the activity of 0.2 IU HCG, were obtained in rats injected with carbon tetrachloride or starved. GIM inhibited the activity of 0.8 IU and 1.6 IU HCG. This was thought to result from the difference in mean final body weight between the GIM and the control groups. The results support the hypothesis that GIM causes a non-specific stress reaction. In rats the effect of this is to increase endogenous gonadotrophin secretion. This contrasts with the results previously reported for mice, which suggest that stress suppresses endogenous follicle-stimulating hormone release.


1970 ◽  
Vol 64 (1) ◽  
pp. 95-102
Author(s):  
L. J. Hipkin

ABSTRACT The activity of human chorionic gonadotrophin (HCG) in the mouse uterus assay depends on the secretion of endogenous gonadotrophin. This source of gonadotrophin is suppressed when the animals are starved or injected with toxic substances, and the response to HCG is therefore inhibited. There is good evidence that this is the mode of action of the urinary gonadotrophin inhibitor (GIM). Since it has been claimed that stress-induced inhibition of gonadotrophin secretion is related to alterations in adrenocortical function, the present investigation is concerned with the response to HCG in animals with experimental hyper- and hypoadrenocorticalism. ACTH gel (300 mU) and a depot form of synthetic ACTH (15 μg) augmented the uterine weight response to HCG (0.5 IU). Normal responses were obtained in animals treated with HCG and either cortisol (300 μg), corticosterone (300 μg) or dehydroepiandrosterone (300 μg). Bilateral adrenalectomy produced similar effects to those previously described for GIM and stressful stimuli, namely, inhibition of HCG activity but no impairment of the responses to follicle-stimulating hormone (FSH), HCG given with FSH, or oestrone. It was thought that these results were produced by the metabolic and traumatic effects of the operation rather than by increased secretion of ACTH per se. Cortisol, corticosterone and ACTH gel did not influence the effect of GIM on HCG activity in the mouse uterus assay. The results suggest that suppression of endogenous gonadotrophin secretion following acute stress is not secondary to increased secretion of ACTH or hyperfunction of the adrenal cortex.


1974 ◽  
Vol 75 (1) ◽  
pp. 141-147 ◽  
Author(s):  
L. J. Hipkin

ABSTRACT Dehydroepiandrosterone (DHA) augments the activity of human chorionic gonadotrophin (HCG) in the rat by increasing endogenous pituitary gonadotrophin secretion. The following experiments were undertaken to investigate the mechanism underlying this effect. Androstenedione (40 μg), dihydrotestosterone (200 μg) and testosterone (200 μg) augmented the rat uterine weight response to 0.5 IU of HCG. At these doses, the steroids did not affect basal uterine weight although this was increased when 1 mg of a steroid was injected. Androsterone (1 mg), 17α-hydroxypregnenolone (1 mg) and progesterone (200 μg) neither augmented HCG activity nor increased basal uterine weight. Ovarian weight differences were not significant in any of the experiments. Androstenedione, DHA, dihydrotestosterone and testosterone (200 μg dose level) did not significantly affect the uterine weight of castrated animals, and responses to 0.04 μg of oestradiol were not potentiated. The results with androstenedione, dihydrotestosterone and testosterone are identical to those obtained with DHA and suggest that these steroids may also increase pituitary gonadotrophin secretion.


1970 ◽  
Vol 65 (3) ◽  
pp. 552-564
Author(s):  
L. J. Hipkin

ABSTRACT Boiled urinary extracts, which had inhibited the activity of human chorionic gonadotrophin (HCG) in the mouse uterus assay, potentiated the effects of HCG and follicle-stimulating hormone (FSH) in the ovarian ascorbic acid depletion and rat ovarian augmentation assays respectively. This treatment inhibited responses to FSH when the ovarian augmentation assay was conducted in hypophysectomised animals. A toxic urinary extract did not affect the activity of HCG in the ventral prostate weight assay in either intact or hypophysectomised rats. Reasons for the different effects of boiled urinary extracts in these assays are discussed.


1970 ◽  
Vol 65 (3) ◽  
pp. 459-465
Author(s):  
E. T. Bell ◽  
D. W. Christie

ABSTRACT The technique of Casellato et al. (1967) for the bioassay of follicle-stimulating hormone (FSH) involving the reduction of 2,3,5-triphenyltetrazolium chloride in the vagina of the immature mouse following the administration of FSH and human chorionic gonadotrophin (HCG) has been studied. In initial experiments it was found that FSH administration did not cause a consistent increase in tetrazolium reduction. Accordingly, modifications to the method involving the dosage of HCG, the time of tetrazolium injection and the time of autopsy after tetrazolium administration have been studied. It was concluded that in the mouse colony employed the tetrazolium assay could not be established.


1955 ◽  
Vol 13 (1) ◽  
pp. 59-64 ◽  
Author(s):  
P. S. BROWN

SUMMARY Two convenient bioassays of urinary gonadotrophins, using immature mice, are described. The first is based upon the initial doubling of uterine weight. The second, using the ovarian weight response, attempts to increase specificity to follicle stimulating hormone by priming with human chorionic gonadotrophin. The usefulness of both methods is discussed, and the influence of non-specific impurities during the assay of urinary extracts is stressed.


1966 ◽  
Vol 34 (1) ◽  
pp. 41-50 ◽  
Author(s):  
D. R. LANG ◽  
D. R. LAMOND

SUMMARY Deprivation of food for 24–48 hr. before the injection of gonadotrophin into mice reduced mean uterine weights and the slopes of the dose-response lines; the effect was greater with human chorionic gonadotrophin (HCG) than with pregnant mare serum gonadotrophin. Age and time of weaning relative to the injection of gonadotrophin, and the number of experimental mice per cage, also affected the uterine weight response. Age and weight influenced the number of ovulations after injections of HCG. Fasting for 48 hr. before the priming injection reduced numbers of ovulations as compared with a restricted diet or fasting for 48 hr. after priming. The time of day of the priming and ovulatory injections influenced the number of ovulations, injections in the afternoon resulting in more ova than injections in the morning.


1971 ◽  
Vol 67 (3) ◽  
pp. 463-469 ◽  
Author(s):  
L. J. Hipkin

ABSTRACT The activity of human chorionic gonadotrophin (HCG) in the mouse uterus assay is augmented by the daily injection of corticotrophin (ACTH). This phenomenon has been further investigated in the rat. Synthetic ACTH (75μg) and dehydroepiandrosterone (1.0 mg) augmented responses to 0.1 IU, 0.2 IU and 0.4 IU HCG in the rat uterus assay. The basal uterine weight was also elevated by the treatment. This effect could not be demonstrated in castrated or hypophysectomised animals, and in the latter the response to HCG was not augmented. Cortisone and corticosterone did not affect HCG assay. Cortisone administration did not suppress the augmenting effect of either carbon tetrachloride or urine extract administration on HCG activity. Mean uterine weights from bilaterally adrenalectomised rats were significantly higher than those from intact or sham operated animals. The results are discussed with reference to the augmentation of HCG activity produced by non-specific stressful procedures.


1957 ◽  
Vol 16 (1) ◽  
pp. 86-97 ◽  
Author(s):  
P. J. CLARINGBOLD ◽  
D. R. LAMOND

SUMMARY The assay of gonadotrophic preparations by means of the uterine weight of the immature mouse has been studied using a preparation of chorionic gonadotrophin. An optimum biological assay, with a linear segment of the log dose-log response line covering a twenty-fold dose range is obtained if the following conditions are fulfilled: (i) The total dose is administered 44 hr prior to killing. (ii) Mice of similar body weight and age are used immediately after weaning. (iii) Responses are corrected by covariance for variation in body weight. Significant secular variation in both position and slope of the dose-response line occurs. It is stressed that adoption of factorial methods of experimentation considerably facilitates the development of a biological assay technique.


1962 ◽  
Vol 24 (2) ◽  
pp. 153-158 ◽  
Author(s):  
H. SCHMIDT-ELMENDORFF ◽  
J. A. LORAINE ◽  
E. T. BELL

SUMMARY The luteinizing hormone (LH), follicle-stimulating hormone (FSH) and 'total gonadotrophic' activities of various hormones have been studied following incubation with 6 m urea at 40° c for 24 hr. LH activity was estimated by the ovarian ascorbic acid depletion test in rats, FSH activity by the augmentation test in mice, and 'total gonadotrophic' activity by the mouse uterus test. Following incubation with 6 m urea the LH activities of NIH—LH, NIH—FSH, human chorionic gonadotrophin and Pergonal were almost completely destroyed, while the LH activity of pregnant mares' serum gonadotrophin (PMSG) was reduced to a smaller extent. The FSH activity of NIH—FSH was little affected by this form of treatment, but in the case of Pergonal a considerable reduction of FSH activity occurred. The 'total gonadotrophic' activity of NIH—FSH, PMSG and Pergonal was reduced after incubation with 6 m urea, the degree of inactivation being greatest in the case of Pergonal. After control incubations with water no appreciable loss of biological activity was observed with any hormone other than Pergonal.


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