Precocious ovulation induced by human chorionic gonadotrophin in the immature female rat: comparison of follicle growth induced by treatment with human chorionic gonadotrophin and by electrical stimulation of the hypothalamus

1985 ◽  
Vol 106 (1) ◽  
pp. 61-66 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
P. Osman
Keyword(s):  
Electrical Stimulation ◽  
Ovarian Follicle ◽  
Treated Group ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Female Rats ◽  
Female Rat ◽  
Follicle Growth ◽  
Immature Female ◽  
Stimulation Of

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

FOLLICLE STIMULATING HORMONE-LIKE ACTIVITY IN HUMAN CHORIONIC GONADOTROPHIN PREPARATIONS

1969 ◽  
Vol 60 (1) ◽  
pp. 137-156 ◽  
Author(s):  
C. Robyn ◽  
P. Petrusz ◽  
E. Diczfalusy
Keyword(s):  
Follicle Stimulating Hormone ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Female Rats ◽  
Immature Female ◽  
Ovarian Weight ◽  
Wide Range ◽  
Immature Rats ◽  
Stimulation Of ◽  
Stimulating Hormone

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.

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
Keyword(s):  
Single Injection ◽  
Direct Action ◽  
Follicular Development ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Female Rats ◽  
Uterine Weight ◽  
Control Value ◽  
Orally Active ◽  
Stimulation Of

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.

ANTERIOR PITUITARY SENSITIVITY IN IMMATURE FEMALE RATS STIMULATED WITH GONADOTROPHIN RELEASING HORMONE IN VIVO: EFFECT OF PRIMING WITH OESTROGEN, PREGNANT MARE SERUM GONADOTROPHIN OR BRAIN LESION

1977 ◽  
Vol 74 (1) ◽  
pp. 99-109 ◽  
Author(s):  
D. DE ZIEGLER ◽  
M. WILKINSON ◽  
DANIELLE CASSARD ◽  
K. B. RUF
Keyword(s):  
Brain Lesion ◽  
Treated Group ◽  
Female Rats ◽  
Similar Degree ◽  
Female Rat ◽  
Immature Female ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Pregnant Mare Serum Gonadotrophin

An investigation of pituitary sensitivity, assessed in terms of increments in plasma LH and FSH concentrations, to stimulation with one or two injections of gonadotrophin releasing hormone (GnRH) was carried out on 26-day-old immature female rats which had received one of the following priming treatments: 10 μg oestradiol benzoate (OB) as a single injection on day 23 or day 25, or on both days; 10 i.u. pregnant mare serum gonadotrophin (PMSG) on day 24; an electrochemical brain lesion placed in the mediobasal hypothalamus on day 23; control animals received either vehicle alone or a sham lesion. Pituitary sensitivity assessed at 10.00 h on day 26, after one or two injections of GnRH (100 ng/100 g body weight, s.c.), was enhanced to a similar degree in the three groups treated with OB in terms of LH (P < 0-01). The FSH response also increased after OB treatment but was not statistically significant. In contrast, 48 h after the injection of PMSG (i.e. when the rats were in a 'pro-oestrous-like' condition) pituitary sensitivity in terms of both LH and FSH dropped sharply (P < 0·001). In lesioned animals, pituitary sensitivity to one injection of GnRH was unchanged. A second GnRH injection administered after a 60 min interval induced a slightly larger LH response in control animals. In contrast, the ratio of the second response to the first increased in animals treated with PMSG, despite the state of overall decrease in sensitivity, being 4·5:1 in PMSG-treated rats versus 1·4:1 in controls. In a second set of experiments, we investigated the variation of pituitary sensitivity in conjunction with an experimentally induced gonadotrophin surge. In animals treated with OB on day 23 and with 1 mg progesterone at 12·00 h on day 26, pituitary sensitivity was increased at both 14.00 and 17.00 h as compared with that in the day 23 OB-treated group at 10.00 h. The PMSG-treated animals maintained their state of decreased responsiveness at 14.00 h, but exhibited increased pituitary sensitivity at the time of the gonadotrophin surge (17.00 h). These results show that OB increases pituitary sensitivity to GnRH in 26-day-old female rats and that the induction of a gonadotrophin surge further increases this sensitivity. In contrast, PMSG-treated rats displayed a state of decreased responsiveness 48 and 52 h, but not 55 h, after the injection. Pituitary sensitivity on the second day after PMSG treatment thus clearly differs from that observed during pro-oestrus in the adult cyclic female rat.

Initial ovulation rate and follicle population after injection of inhibin-neutralizing antiserum in the late-prepubertal rat

1991 ◽  
Vol 130 (2) ◽  
pp. 289-296 ◽  
Author(s):  
H. J. Sander ◽  
H. M. A. Meijs-Roelofs ◽  
E. C. M. van Leeuwen ◽  
P. Kramer ◽  
W. A. van Cappellen
Keyword(s):  
Neutralizing Antibodies ◽  
Ovulation Rate ◽  
Female Rats ◽  
Corpora Lutea ◽  
Female Rat ◽  
Follicle Growth ◽  
Immune Control ◽  
Immature Female ◽  
Antral Follicles ◽  
Control Serum

ABSTRACT In late-prepubertal female rats passive immunoneutralization of endogenous inhibin was achieved by injection of inhibin antiserum. Effects on follicle population, timing of sexual maturation, ovulation rate at first and second oestrus and serum FSH levels were studied. Rats were injected with antiserum, (non-immune) control serum from castrated sheep (castrated serum) or their IgG fractions, or with saline on day 33 or 3 or 2 days (days −3/−2) before the expected day of first ovulation, day 38·5±0·2 (n = 70). Blood was collected from different subgroups at 8, 24 and 48 h, and at first and second oestrus after injection. At necropsy, ovaries were histologically prepared for differential counting of follicles (48 h and first oestrus) and counting of corpora lutea (CL; first and second oestrus) as an index of ovulation rate. Results from rats injected with either serum or its IgG fraction were not different, as was the case when rats were injected with either castrated serum or saline. Thus, results from groups treated with antiserum and antiserum IgG were combined and labelled 'antiserum', and the castrated serum, castrated serum IgG and saline-treated groups were combined and labelled 'control'. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by 43% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin. After antiserum injection on day 33, more healthy antral follicles (vol. > 100 × 105 μm3, diameter > 260 μm) were present in the ovaries at 48 h (70·6 vs 54·4; P < 0·05) and at first oestrus (73·1 vs 50·8; P < 0·05) if first oestrus was reached within 5 days, but numbers were not different if first oestrus was more than 5 days after injection (52·6 vs 50·8). The number of CL after injection of antiserum on day 33 was increased at first oestrus compared with control (13·4±0·5, n = 30, vs 10·0±0·2, n = 40; P<0·001), an effect that was even more clearly present in antiserum-injected rats ovulating within 5 days (14·4±0·7, n = 20; P < 0·001). Rats injected with antiserum at days −3/−2 showed a doubling of ovulation rate at first oestrus when compared with control animals (21·5±0·8, n = 12, vs 10·5±0·2, n = 15; P < 0·001). No differences in the number of CL was seen at second oestrus. Age and body weight on the day of first ovulation were not influenced by antiserum treatment. Serum FSH was significantly (P < 0·01) increased at 8 h after antiserum injection on either day 33 or on days −3/−2 to a level of 250 and 800% of control levels respectively. Thus, injection with inhibin–neutralizing antiserum into prepubertal female rats resulted, through an increase in serum FSH concentration 8 h after injection, in the growth of additional numbers of healthy antral follicles. Supranormal ovulation rate occurred if antiserum injections were given within the last 5 days before first ovulation, with a maximal ovulation rate after injection on days −3/−2. The data support the view that, in the immature female rat during the last 5 days before the day of first ovulation, inhibin is (through its regulation of serum FSH levels) progressively involved in the control of follicle growth and ovulation rate. Journal of Endocrinology (1991) 130, 289–296

COMPARISON OF FOLLICLE-STIMULATING HORMONE AND LUTEINIZING HORMONE SECRETION AFTER ELECTRICAL STIMULATION OF THE PREOPTIC PART OF THE HYPOTHALAMUS IN FEMALE RATS ANAESTHETIZED WITH ETHYL CARBAMATE OR SODIUM PENTOBARBITONE

1978 ◽  
Vol 78 (1) ◽  
pp. 151-152 ◽  
Author(s):  
R. G. DYER ◽  
M. B. TER HAAR ◽  
LINDA C. MAYES
Keyword(s):  
Electrical Stimulation ◽  
Luteinizing Hormone ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Control Process ◽  
Female Rats ◽  
Female Rat ◽  
Luteinizing Hormone Secretion ◽  
Stimulation Of ◽  
Stimulating Hormone

A.R.C. Institute of Animal Physiology, Babraham, Cambridge, CB2 4AT (Received 17 January 1978) For over 30 years, the method by which the brain regulates the secretion of gonadotrophic hormones has been studied by electrical stimulation of those parts of the central nervous system thought to be implicated in the control process. Much of the work has been performed on the female rat. In this species, anaesthetic doses of sodium pentobarbitone, administered immediately before the pro-oestrous 'critical period', block the preovulatory surge of luteinizing hormone (LH) for 24 h. The same treatment also reduces the early phase of the pro-oestrous secretion of follicle-stimulating hormone (FSH; Daane & Parlow, 1971). Electrical stimulation of the preoptic part of the hypothalamus can overcome this blocking effect and analysis of the optimum parameters required to restore normal secretion of gonadotrophins may give some insight into the endogenous process (e.g. Everett, 1965; Fink & Aiyer, 1974;

IMMUNOREACTIVE LUTEINIZING HORMONE RELEASING FACTOR IN PITUITARY STALK BLOOD FROM FEMALE RATS: SEX STEROID MODULATION OF RESPONSE TO ELECTRICAL STIMULATION OF PREOPTIC AREA OR MEDIAN EMINENCE

1976 ◽  
Vol 70 (3) ◽  
pp. 501-511 ◽  
Author(s):  
NANCY M. SHERWOOD ◽  
SHARON A. CHIAPPA ◽  
G. FINK
Keyword(s):  
Electrical Stimulation ◽  
Median Eminence ◽  
Preoptic Area ◽  
Neural Mechanism ◽  
Female Rats ◽  
Pituitary Stalk ◽  
Facilitatory Effect ◽  
Sex Steroid ◽  
Female Rat ◽  
Stimulation Of

SUMMARY The effects of sex steroid hormones on the responsiveness of the neural mechanism responsible for the secretion of LH-RF have been examined in the female rat. Responsiveness was determined at pro-oestrus by measuring the increments in immunoreactive LH-RF of pituitary stalk blood produced by electrical stimulation of the medial preoptic area or median eminence. Ovariectomy on the morning of dioestrus reduced the LH-RF response to preoptic stimulation while oestradiol benzoate (OB) or testosterone propionate (TP) administered immediately after ovariectomy significantly augmented the response. The facilitatory effect of TP was possibly due to its conversion to an aromatized derivative since 5α-dihydrotestosterone monobenzoate was ineffective. Progesterone did not facilitate preoptic responsiveness, and, when administered to animals ovariectomized at 12.00 h of pro-oestrus, reduced the LH-RF response at 18.00 h the same day. Stimulation of the median eminence produced a significantly greater increment in LH-RF than stimulation of the preoptic area. The facilitatory action of OB on the LH-RF response was less marked for median eminence compared with preoptic stimulation. The administration of ICI 46474 at 17.00 h of dioestrus did not reduce preoptic responsiveness on the morning of the next day, suggesting that this compound does not act as an 'antioestrogen' at the level of the preoptic area.

THE EFFECT OF CHLORMADINONE ON THE RESPONSE OF THE OVARIES AND UTERUS OF THE IMMATURE RAT TO GONADOTROPHIC STIMULATION

1964 ◽  
Vol 30 (2) ◽  
pp. 235-245 ◽  
Author(s):  
M. J. K. HARPER
Keyword(s):  
Ovarian Response ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Female Rats ◽  
Corpora Lutea ◽  
Immature Female ◽  
Immature Rat ◽  
Orally Active ◽  
Pregnant Mare Serum Gonadotrophin ◽  
Intact Rats

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.

OVULATION INDUCED BY PREGNANT MARE SERUM GONADOTROPHIN IN THE IMMATURE RAT TREATED NEONATALLY WITH A LOW OR A HIGH DOSE OF ANDROGEN

1972 ◽  
Vol 55 (3) ◽  
pp. 533-541 ◽  
Author(s):  
J. Th. J. UILENBROEK ◽  
J. J. van der WERFF ten BOSCH
Keyword(s):  
Testosterone Propionate ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Female Rats ◽  
High Dose ◽  
Immature Female ◽  
Immature Rat ◽  
Progesterone Treatment ◽  
Combined Administration ◽  
Pregnant Mare Serum Gonadotrophin

SUMMARY Ovulation-inducing effects of pregnant mare serum gonadotrophin (PMSG) were studied in immature female rats treated on day 5 (day 1 = day of birth) with oil or with 5 or 1250 μg testosterone propionate (TP). The response of rats treated with 1250 μg TP was negligible regardless of the age of the animals and of the dose of PMSG. The response of rats treated with 5 μg TP to PMSG alone was low (36% of rats, with 2·6 ova/ovulating rat), but could be improved by progesterone administration 2 days after PMSG injection (91% of rats, with 14·5 ova/ovulating rat). At every age and dose of PMSG tested the response of animals treated with 5 μg TP to combined PMSG and progesterone treatment was less than that of control animals. It is concluded that neonatal TP treatment diminishes the release of endogenous ovulating hormone subsequent to PMSG injection. This effect is dependent on the dose of TP used, but already demonstrable in animals treated with 5 μg TP on day 5, which would have been cyclic and fertile after puberty. Only for the animals treated with 1250 μg TP could a decreased sensitivity of the ovaries to combined administration of PMSG and human chorionic gonadotrophin be demonstrated.

UPTAKE OF LABELLED HUMAN CHORIONIC GONADOTROPHIN IN THE BRAIN OF THE ADULT FEMALE RAT

1972 ◽  
Vol 71 (2) ◽  
pp. 245-254 ◽  
Author(s):  
Tsutomu Yaginuma
Keyword(s):  
Cerebral Cortex ◽  
Adult Female ◽  
Median Eminence ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Female Rats ◽  
Current Evidence ◽  
Female Rat ◽  
The Brain ◽  
Brain Tissues

ABSTRACT 125I, 125I-bovine serum albumin (BSA) and 125I-human chorionic gonadotrophin (HCG) were injected intravenously into adult female rats, and the radioactivity in the brain tissues was determined at 1, 2.5 and 4 h. Two and a half and 4 h after the injection of 125I-HCG, the radioactivity in the median eminence was significantly higher than in other tissues investigated, i. e. the anterior, middle and posterior hypothalamus, amygdala and cerebral cortex. Among the latter tissues no differences were found at any time. The radioactivity ratio of the median eminence to the cerebral cortex or plasma after the injection of 125I-HCG increased with time and at 4 h was significantly higher than after the injection of 125I-BSA. Following the administration of 1251 or 125I-BSA, no differences were found in radioactivity among the brain tissues at any time. A considerably higher uptake of radioactivity was observed in the ovary of the same animals 2.5 and 4 h after the injection of 125I-HCG, as compared to that after the injection of 125I or 125I-BSA. This may indicate that labelled HCG well retains its biologocal activity. Most of the radioactive materials taken up in the tissues following the injection of 125I-HCG was shown immunologically to be HCG. These results may indicate that the median eminence has a characteristic ability to take up and retain HCG. This is consistent with current evidence for the internal or short feedback of gonadotrophin to the median eminence.

EFFECT OF ELECTRICAL STIMULATION OF THE HYPOTHALAMUS ON GONADOTROPHIN RELEASE AND THE ONSET OF PUBERTY

1972 ◽  
Vol 54 (2) ◽  
pp. 277-284 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS
Keyword(s):  
Electrical Stimulation ◽  
Precocious Puberty ◽  
Arcuate Nucleus ◽  
Follicle Stimulating Hormone ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Immature Female ◽  
Ovarian Weight ◽  
Stimulation Of ◽  
Stimulating Hormone

SUMMARY Electrical stimulation of the hypothalamus with biphasic pulses was performed in immature female rats. When performed at 27 days of age or later, electrical stimulation in the arcuate nucleus region advanced puberty in all animals, as did stimulation of the anterior hypothalamus at 29 days of age or later. Stimulation in younger rats did not uniformly advance puberty. The responsiveness to electrical stimulation thus seems to develop a few days earlier in the arcuate nucleus region than in the anterior hypothalamus. In a second experiment the possible involvement of follicle-stimulating hormone (FSH) in the advancement of puberty was investigated: the simplified augmented ovarian weight assay for endogenous FSH was performed in rats stimulated in the arcuate nucleus region as well as in controls. A marked increase in ovarian weight, indicating increased FSH levels, was demonstrated in all animals stimulated on day 27 or later; at earlier ages only a percentage of the stimulated animals responded. This percentage paralleled the percentage of animals that showed advancement of puberty. It is concluded that electrical stimulation in both the arcuate nucleus region and the anterior hypothalamus advances the onset of puberty. It is suggested that electrical stimulation causes increased plasma FSH levels and, in consequence, precocious puberty.

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