THE EFFECT OF CORTICOTROPHIN ON THE RAT UTERINE WEIGHT RESPONSE TO HUMAN CHORIONIC GONADOTROPHIN

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.

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.


1965 ◽  
Vol 33 (3) ◽  
pp. 447-454
Author(s):  
M. J. K. HARPER

SUMMARY Administration of chlormadinone, an orally active progestational agent without significant oestrogenic activity, to intact immature female rats did not affect either ovarian or uterine weight significantly compared with controls. A single injection of human chorionic gonadotrophin (HCG) caused a 73 % increase in uterine weight in 24 hr. over the control value. This dose significantly increased ovarian weight and although it caused some stimulation of follicular development, ovulation during this time did not occur. When animals were treated with chlormadinone for 8 days, and received HCG on the 8th day, uterine weight was 170% greater than in the controls and 56% greater than with HCG alone. The uterine weight produced was similar to that found in animals treated with mestranol, a potent oestrogen, and HCG. In ovariectomized animals HCG did not affect uterine weight, while the small increase produced by chlormadinone was unaltered when HCG also was given. Mechanisms are discussed by which this augmentation of the uterine response to HCG might be produced. It seems most likely that chlormadinone administration causes storage of endogenous gonadotrophin in the pituitary, and that the exogenous gonadotrophin acts as the 'trigger' for the release of stored hormone, probably by a direct action on the hypothalamus.


1969 ◽  
Vol 61 (1) ◽  
pp. 89-95
Author(s):  
Rudi Borth ◽  
Annette Menzi

ABSTRACT In a study designed as a factorial experiment, the biological activity of standard solutions of human chorionic gonadotrophin in distilled water (A), saline (B), 1 % bovine serum albumin (C), 0.5 % gelatin (D), and borate buffer of pH 9 (E) was investigated under four different conditions of freezing and thawing, using the following three methods of bioassay: ovarian ascorbic acid depletion in rats (OAAD), uterine weight in mice (UW), and ovarian hyperaemia in rats (OH). Repeated freezing and thawing and prolonged storage at -15°C did not affect the potency in any test. In the OAAD test, the potency was increased 4–5fold by D, and 2–3fold by C. In the OH test, E augmented the potency 2–3fold. These findings are of interest in the practice of bioassay, in studying mechanisms of response, and regarding administration for therapeutic purposes. Diluents which possess augmenting properties could be used to improve the sensitivity of a bioassay if standard and unknowns showed the same degree of augmentation.


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.


1961 ◽  
Vol 21 (4) ◽  
pp. 459-467 ◽  
Author(s):  
R. B. DONNELLY ◽  
G. M. STONE

SUMMARY The method of assay for gonadotrophin developed by Claringbold & Lamond (1957) has been found satisfactory and suitable for a wide range of management conditions and strains of mice. It has been confirmed that this method gives similar slopes for human chorionic gonadotrophin and pregnant mares' serum and it has been found, in addition, that these slopes do not differ from strain to strain. An explanation is offered of the contrary results of Brown, Cunningham & Finegan (1959) and some comments are made on the design and analysis of assays, particularly the selection of dose ranges. It is considered that the uterine weight assay offers no evidence for the existence of two separate gonadotrophic principles.


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.


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