AUGMENTATION BY CHLORMADINONE OF THE UTERINE WEIGHT RESPONSE TO HUMAN CHORIONIC GONADOTROPHIN IN INTACT IMMATURE RATS

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 60 (1) ◽  
pp. 137-156 ◽  
Author(s):  
C. Robyn ◽  
P. Petrusz ◽  
E. Diczfalusy

ABSTRACT The follicle stimulating hormone (FSH)-like activity of human chorionic gonadotrophin (HCG) preparations was assayed by the method based on the ovarian weight augmentation in intact immature rats. The potencies ranged from 4.8 to 7.4 IU equivalents of FSH per mg. The FSH-like potency of the Second International Standard Preparation of HCG was 8.5 IU per vial. However, when in intact immature rats the ovarian weight response to HCG preparations was compared at a wide range of doses (40 to 51 200 IU) to that obtained with a human menopausal gonadotrophin (HMG) preparation (0.5 to 128 IU of FSH) in the presence of 40 IU of HCG, significant differences were found. The assays conducted in hypophysectomised immature female rats were invalid, because of lack of parallelism. Antisera were prepared by immunising rabbits with HCG and human hypophysial gonadotrophin (HHG) preparations and the antigonadotrophin profiles (HCG-, FSH- and FSH-like neutralising potencies) of these antisera were established by the use of statistically valid bioassay procedures. The anti-HCG and anti-HHG sera neutralised the FSH activity of HMG preparations as well as the FSH-like activity of HCG preparations. However, 3 to 175 times more antiserum was required to neutralise the equivalent of 1.0 IU of FSH-like activity present in HCG than expected on the basis of the anti-FSH potency of the antisera. On the other hand, there was a high degree of correlation between the neutralising potencies of the antisera when tested against the FSH-like activity and the HCG activity of various HCG preparations. When the FSH-like activity of an HCG preparation was quantitatively neutralised with an anti-HCG serum, some 30 per cent of the HCG activity remained unneutralised, as evidenced by repeated bioassays. Although at least 2000 IU of this »FSH-free« HCG was administered to groups of intact as well as hypophysectomised immature female rats, this high dose of HCG did not induce an increase in ovarian weight beyond that elicited by 40 IU of untreated HCG. Histological examination of the ovaries indicated lack of follicle stimulation in the hypophysectomised, but not in the intact immature animals. There was an excessive stimulation of the interstitial cells in both types of animals. The data indicate that the FSH-like activity of HCG preparations is neither due to a contamination by FSH of pituitary origin, nor is it an evenly distributed intrinsic property of the HCG molecules. It is also concluded that the gonadotrophic activity of biologically pure HCG in immature hypophysectomised female rats consists of a specific stimulation of the interstitial cell apparatus. Such HCG preparations do not induce any follicle stimulation, not even when administered in excessive doses.


1964 ◽  
Vol 30 (2) ◽  
pp. 235-245 ◽  
Author(s):  
M. J. K. HARPER

SUMMARY The effects of chlormadinone (6-chloro-Δ6-17α-acetoxyprogesterone), an orally active progestational agent without significant oestrogenic activity, on the response of the ovaries of intact and hypophysectomized immature female rats to exogenous gonadotrophin have been examined. Administration of the steroid whether starting on the same day as, or 4 days before treatment with gonadotrophin, did not depress the ovarian response in intact rats. In hypophysectomized animals, pretreated with the progestagen, the ovarian response to gonadotrophin was depressed. In intact rats, treatment with the steroid and pregnant mare serum gonadotrophin (PMSG) resulted in ovulation, whereas in similar animals given PMSG alone no corpora lutea were found. Corpora lutea were seen in all groups given PMSG and human chorionic gonadotrophin (HCG) but ovulation occurred earlier when, in addition, treatment with the steroid was included. In only one experiment with intact rats did administration of the steroid alone cause a significant increase in uterine weight compared with controls. In neither experiment on hypophysectomized animals did such an increase occur, and significant decreases were recorded.


1965 ◽  
Vol 33 (1) ◽  
pp. 13-23 ◽  
Author(s):  
G. S. GREENWALD

SUMMARY A single injection of 0·25 mg. stilboestrol or 5 mg. progesterone at metoestrus (day 1) affected follicular development in the hamster ovary in different ways. Stilboestrol induced widespread follicular atresia but apparently did not interfere with the release of ovulating hormone at the end of the oestrous cycle. The atresia produced by stilboestrol appears to be mediated by changes in the levels of circulating gonadotrophin rather than by a direct effect on the ovary. This was demonstrated by injecting pregnant mare serum on day 1 of the cycle followed by stilboestrol treatment at various times thereafter. Under these circumstances the ovulation rate was only reduced below control values when stilboestrol was injected on day 1. Progesterone given on day 1 of the cycle did not interfere with the maturation of healthy Graafian follicles but acted on the terminal stages of follicular growth by blocking ovulation. After a single injection of progesterone, the life span of antral follicles was prolonged to 8–9 days. The ovulation-inhibiting effects of progesterone given on day 1 of the cycle were overcome by the injection of human chorionic gonadotrophin on day 4. Thus, progesterone blocked ovulation indirectly by preventing release of ovulating hormone from the anterior pituitary. The effects of shifting the single injection of stilboestrol or progesterone to the other days of the oestrous cycle are also considered.


1985 ◽  
Vol 106 (1) ◽  
pp. 61-66 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
P. Osman

ABSTRACT Precocious first ovulation, preceded by an endogenous preovulatory LH surge, could be predictably induced in immature female rats by administering repeated injections of human chorionic gonadotrophin (hCG). Administration of a dose of 0·05–0·075 i.u. hCG, four times a day from day 28 to day 31 of age resulted in a highly constant ovulatory response: at 4·0±0·0 days after the start of treatment 7·7±0·3 (n = 15) ova were found. Use of a higher dose of hCG (0·1 i.u.) resulted in lower numbers of ova (5·6±0·4, n = 7; P<0·005) whereas use of a lower dose of hCG (0·025–0·038 i.u.) resulted in a less constant timing of the induced ovulation at 5·4±0·2 days after the start of treatment (n = 7; P<0·0005). In animals treated with the dose of 0·05–0·075 i.u. hCG, a positive correlation was found between body weight at the start of treatment and the number of ova released (r = 0·75, n = 25; P<0·001). Ovarian follicle dynamics were studied on the various days of hCG treatment (dose 0·05–0·075 i.u.) and compared with the follicle changes that take place after electrical stimulation of the hypothalamus, performed on day 28, a treatment known to result in first ovulation 4–5 days later. In both groups a decrease in the number of the smallest and the middle-sized antral follicles as compared with their respective controls was seen, whereas numbers of follicles in the largest, 'ovulatable' size classes gradually increased. The pattern was more conspicuous in the hCG-treated group, presumably related to greater constancy in timing of the ovulatory response in this group. The present data support the view that endogenous changes in LH secretion during late prepuberty (which have been found to take place) play a significant role in stimulating late-prepubertal follicle growth and the ensuing first ovulation. J. Endocr. (1985) 106, 61–66


1966 ◽  
Vol 51 (2) ◽  
pp. 269-280 ◽  
Author(s):  
Donald C. Johnson

ABSTRACT The gonads and accessory sex organs of hypophysectomized male or female rats were used to evaluate the gonadotrophin content of the plasma from a non-castrate parabiotic partner. Ovarian follicular development and the human chorionic gonadotrophin augmentation reaction indicated the presence of FSH in the plasma of immature males. LH was apparent by androgen production from testes in hypophysectomized male partners. The amount of LH was reduced by 2 mg progesterone or 20 μg testosterone propionate (TP) and increased by administration of hypothalamic extract daily to the intact male. Bilateral cryptorchidism also quickly elevated the plasma LH level. FSH output, as measured by follicular development in females, was not significantly affected by 50 μg TP or 2 μg oestradiol daily for 10 days. Females had little gonadotrophin in their plasma since hypophysectomized female partners showed only slight ovarian and no uterine stimulation. The increased gonadotrophins associated with unilateral compensatory hypertrophy, however, was quickly manifested in follicular hypertrophy and abundant oestrogen production in the hypophysectomized partner.


1992 ◽  
Vol 18 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Omar Caticha ◽  
Sanjeev Grover ◽  
Dennis Winge ◽  
William D. Odell

1978 ◽  
Vol 89 (1) ◽  
pp. 166-172 ◽  
Author(s):  
T. J. Weiss ◽  
D. T. Armstrong ◽  
J. E. A. McIntosh ◽  
R. F. Seamark

ABSTRACT Theca and granulosa tissues isolated from sheep ovarian follicles of different sizes were incubated in the presence of human chorionic gonadotrophin (HCG; 5 IU/ml) or follicle stimulating hormone (FSH; 5 μg NIH-FSH-S11/ml) for 40 min. Changes in the total amounts of cyclic 3′,5′-adenosine monophosphate (cAMP) were used as an index of the responsiveness of these preparations to the hormones. Thecal tissue of both large (4–6 mm in diameter) and small (1–3 mm) follicles responded similarly to gonadotrophins. Granulosa cells from small follicles failed to respond to stimulation by HCG. FSH, however, consistently increased cAMP production in comparison with controls or cells treated with HCG. Granulosa cells of large follicles responded to both HCG and FSH.


Author(s):  
N. Walker ◽  
P. J. Burnett

Puberty can be stimulated from about 160 days of age by the introduction of a mature boar usually in accomodation which is novel to the gilt. The interval between stimulation and response is not always predictable and therefore does not facilitate the synchronisation of gilt matings with the mating pattern in an established sow herd. It has been reported previously that a single injection of pregnant mares’ serum gonadotrophin (PMSG) pits human chorionic gonadotrophin (HCG)* will initiate puberty. The investigations reported here concern the use of these exogenous hormones as an additional or alternative stimulus to those described above.


1985 ◽  
Vol 38 (4) ◽  
pp. 445 ◽  
Author(s):  
Y M Hodgson ◽  
DM de Kretser

The testosterone responses to a single injection of HCG (100 i.u.) in hypophysectomized (hypox.), cryptorchid or sham-operated rats were followed over a 5-day period. In sham-operated rats, hCG induced a biphasic rise in serum testosterone, peaks being observed at 2 and 72 h. Reduced testis weights, elevated FSH and LH levels and reduced serum testosterone levels were found after 4 weeks of cryptorchidism, but hCG stimulation resulted in a normal 2 h peak in serum testosterone. However, the secondary rise at 72 h in cryptorchid rats was significantly lower than sham-operated rats.


1995 ◽  
Vol 146 (1) ◽  
pp. 169-176 ◽  
Author(s):  
H Kishi ◽  
K Taya ◽  
G Watanabe ◽  
S Sasamoto

Abstract Plasma and ovarian levels of inhibin were determined by a radioimmunoassay (RIA) at 3-h intervals throughout the 4-day oestrous cycle of hamsters. Plasma concentrations of FSH, LH, progesterone, testosterone and oestradiol-17β were also determined by RIAs. In addition, hamsters were injected at various times with human chorionic gonadotrophin (hCG) to determine the follicular development. The changes in plasma concentrations of FSH after injection of antisera to oestradiol-17β (oestradiol-AS) and inhibin (inhibin-AS) on the morning of day 2 (day 1=day of ovulation) were also determined. Plasma concentrations of inhibin showed a marked increase on the afternoon of day 1, remained at plateau levels until the morning of day 4, then increased abruptly on the afternoon of day 4 when preovulatory LH and FSH surges were initiated. A marked decrease in plasma concentrations of inhibin occurred during the process of ovulation after the preovulatory gonadotrophin surges. An inverse relationship between plasma levels of FSH and inhibin was observed when the secondary surge of FSH was in progress during the periovulatory period. Plasma concentrations of oestradiol-17β showed three increase phases and these changes differed from those of inhibin. Changes in plasma concentrations of oestradiol-17β correlated well with the maturation and regression of large antral follicles. Follicles capable of ovulating following hCG administration were first noted at 2300 h on day 1. The number of follicles capable of ovulating reached a maximum on the morning of day 3 (24·8± 0·6), and decreased by 0500 h on day 4 (15·0 ± 1·1), corresponding to the number of normal spontaneous ovulations. Plasma concentrations of FSH were dramatically increased within 6 h after inhibin-AS, though no increase in FSH levels was observed after oestradiol-AS. These findings suggest that changes in the plasma levels of inhibin during the oestrous cycle provide a precise indicator of follicular recruitment, and that the changes in plasma concentrations of oestradiol-17β are associated with follicular maturation. These findings also suggest that inhibin may play a major role in the inhibition of FSH secretion during the oestrous cycle of the hamster. Journal of Endocrinology (1995) 146, 169–176


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