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

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.

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 (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.


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.


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.


1978 ◽  
Vol 89 (3) ◽  
pp. 492-505 ◽  
Author(s):  
D. M. Robertson ◽  
H. Suginami ◽  
H. Hernandez Montes ◽  
C. P. Puri ◽  
S. K. Choi ◽  
...  

ABSTRACT The presence of an hCG-like material in urinary and pituitary extracts and plasma obtained from non-pregnant subjects was investigated. Two assay methods were used to detect this material following fractionation of pituitary and urinary extracts by gel filtration (Ultrogel AcA 54) and/or isoelectrofocusing: a) a radioimmunoassay employing an antiserum raised against a specific sequence of the carboxy terminal region (residues 115– 145) of the β-subunit of hCG, and b) an in vitro bioassay method which measures both hLH and hCG activities. The fractionation procedures employed provide a satisfactory separation of highly purified hCG and hLH preparations. In the pituitary and urinary extracts hCGβ-peptide-like immunoactive (PIA) material was found consistently, which co-eluted with iodinated hCG following gel filtration and possessed pI values similar to those of hCG when subjected to isoelectrofocusing. The PIA material also exhibited in vitro biological activity similar to that shown by hLH and hCG. Detectable levels of immunoactive material were also found in plasma; however, the plasma levels of this PIA material were not influenced by classical endocrine measures such as the stimulation or inhibition of gonadotrophin secretion. The low levels of this material in plasma precluded its further characterization by gel filtration or electrofocusing. Whereas the present data and those reported by other investigators seem to suggest the presence of some hCG-like material in urinary and pituitary extracts and possibly in plasma of non-pregnant subjects, it is emphasized that the available evidence is not sufficiently conclusive to exclude other interpretations as to the nature of this material.


1999 ◽  
Vol 163 (2) ◽  
pp. 255-260 ◽  
Author(s):  
L Hinojosa ◽  
R Chavira ◽  
R Dominguez ◽  
P Rosas

The effects of thymulin administration beginning on days 19 or 24 of age on spontaneous puberty and gonadotrophin-induced ovulation were analysed in female normal and hypothymic mice. In normal and hypothymic mice, the daily administration of thymulin at 24 days of age resulted in a delay in the age of vaginal opening, with an increase in serum progesterone levels. Normal mice treated with 200 ng thymulin beginning on day 19 of age and injected with pregnant mare serum gonadotrophin (PMSG) 24 h later had an increase in ovulation rate, number of ova shed and weight of the ovaries. None of the hypothymic mice treated with thymulin on day 19 and PMSG on day 20 ovulated. PMSG treatment on day 25 induced ovulation in hypothymic mice. When these animals were injected previously with 200 ng thymulin, the number of ova shed by ovulating animals was lower than in PMSG-treated animals. Administration of thymulin and sequential injection of PMSG and human chorionic gonadotrophin 54 h later resulted in an increase in ovulatory response in comparison with those receiving only PMSG. The results suggest that thymulin plays a role in the regulation of spontaneous puberty through its effects on adrenal and ovarian endocrine functions. The increase in the ovarian PMSG response-treated animals, previously given thymulin, showed that this thymic hormone participates in the regulation of gonadotrophin secretion mechanisms and seems to be dose- and age-dependent. In hypothymic mice, neuroendocrine mechanisms regulating puberty are different from those of normal mice.


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.


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