Inhibition of first ovulation: administration of an LHRH antagonist to immature female rats

1987 ◽  
Vol 112 (3) ◽  
pp. 407-415 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
W. A. van Cappellen ◽  
G. A. Schuiling

ABSTRACT Subcutaneous injections of an LHRH antagonist (ALHRH; Org.30093) were administered to immature female rats. Neither a single high dose (50 μg) nor repeated daily doses of 5–30 μg ALHRH/day, administered between 28 and 38 days of age, influenced the age and body weight at the time of vaginal opening or first ovulation. If repeated daily doses of 2 × 10 μg ALHRH were given from 32 to 42 or from 37 to 47 days of age, first ovulation was delayed by 3·0 and 6·3 days respectively. Administration of 10 μg ALHRH at 09.00 h and again at 17.00 h on the day of first pro-oestrus was found to be sufficient to block the expected first ovulation in 36 out of 38 rats. This effect could be repeated by administering the same doses of ALHRH at pro-oestrus and again on the next day: ovulation was blocked in eight out of eight rats. A single dose of 10 μg ALHRH, administered on the morning of pro-oestrus, blocked ovulation in five out of twelve rats. Both the preovulatory LH and FSH surge, as measured at 16.00 h on pro-oestrus, were found to be inhibited by ALHRH treatment. On the day after pro-oestrus no recruitment of new small antral follicles had occurred in rats with ovulatory blockade. Delayed ovulation took place 2–5 days after ALHRH injection at pro-oestrus; until 3 days after injection rats were able to ovulate their original preovulatory follicles, thereafter newly developed follicles ovulated and large ovarian cysts were found in the ovaries, next to fresh corpora lutea. Chronic administration of two injections daily of 10 μg ALHRH from 34 days of age until the morning of first pro-oestrus had marginal effects on the timing of first pro-oestrus and on follicle dynamics. It was concluded that with the ALHRH compound used, and in chronic as well as in acute experiments, first ovulation could only be delayed by its administration on the day of first pro-oestrus and that the effect was due to acute inhibition of the preovulatory gonadotrophin surge. J. Endocr. (1987) 112, 407–415

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

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


1982 ◽  
Vol 100 (1) ◽  
pp. 105-108 ◽  
Author(s):  
Günter Emons ◽  
Peter Ball

Abstract. This study was designed to test the ability of 2- and 4-hydroxyoestrogens to induce ovulations and the formation of corpora lutea in immature female rats. To this end 25 day old animals received a single injection of different doses of either 4-hydroxyoestradiol-dibenzoate (10, 25, 50 μg) or 2-hydroxyoestradiol-dibenzoate (25, 250 μg) or oestradiol-benzoate (10, 25, 50 μg). On day 31 the ovaries were checked for corpora lutea. 4-Hydroxyoestradiol-dibenzoate and oestradiol-benzoate in doses of 50 or 25 μg significantly increased the number of animals with corpora lutea whereas animals treated with 10 μg of either steroid did not differ significantly from the respective vehicle groups. 2-Hydroxyoestradioldibenzoate, even at the high dose of 250 μg did not show a significant effect. This is the first demonstration that a catecholoestrogen 4-hydroxyoestradiol - can induce ovulation. As its potency in doing so is similar to that of oestradiol and as 4-hydroxyoestradiol can be formed in neuroendocrine tissues from primary oestrogens, we conclude that this catecholoestrogen might play a role in the regulation of ovulation.


Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4226-4237 ◽  
Author(s):  
Verónica Outeiriño-Iglesias ◽  
Marina Romaní-Pérez ◽  
Lucas C. González-Matías ◽  
Eva Vigo ◽  
Federico Mallo

Control of estrous cycle and reproductive capacity involves a large number of central and peripheral factors, integrating numerous nutritional and metabolic signals. Here we show that glucagon-like peptide-1 (GLP-1), a peptide with anorexigenic and insulinotropic actions, and the GLP-1 receptor agonist Exendin-4 (Ex4) exert a regulatory influence on the gonadal axis, in both adult and prepubertal female rats. In adult rats, Glp-1 receptor expression varies during the estrous cycle at the hypothalamus, pituitary, and ovary. Furthermore, acute treatment with GLP-1 in the morning proestrus doubled the amplitude of the preovulatory LH surge, as well as influencing estradiol and progesterone levels along the estrous cycle. These changes provoked an important increase in the number of Graafian follicles and corpora lutea, as well as in the litter size. Conversely, Ex4 diminished the levels of LH, later producing a partial blockade at the preovulatory surge, yet not affecting either the number of mature follicles or corpora lutea. Chronic administration of low doses of GLP-1 to prepubertal rats synchronized vaginal opening and increased LH levels on the 35th day of life, yet at these doses it did not modify their body weight, food intake, or ovarian and uterine weight. By contrast, chronic exposure to Ex4 produced a significant reduction in ovarian and uterine weight, and serum LH, and the animals treated chronically with Ex4 showed no vaginal opening in the period studied. Overall, our results demonstrate that GLP-1 and Ex4 act on the gonadal axis, involving the hypothalamic kisspeptin system, to influence reproductive efficiency in female rats.


Zygote ◽  
2021 ◽  
pp. 1-7
Author(s):  
Stéphanie Ouabo Meguem ◽  
Landry Lienou Lienou ◽  
Marie Stéphanie Chekem Goka ◽  
Richard Simo Tagne ◽  
Didiane Mefokou Yemele ◽  
...  

Summary Dicliptera verticillata is a medicinal plant traditionally used in western Cameroon to cure female infertility. This experiment was designed to assess the effects of the aqueous extract of Dicliptera verticillata (AEDv) on fertility and gestation in female rats. Oral increasing doses of AEDv were administered to immature female rats over 20 d. After this time, some animals were mated with fertile males and some fertility parameters were assayed; the other animals were euthanized for preliminary toxicity parameters analysis. The effects of AEDv on the different stages of gestation were assayed on selected animals previously controlled for estrous cycle regularity and mated. AEDv led to an increase in serum, uterine and ovarian proteins as well as in ovarian and uterine weights (P < 0.05) in immature female rats. Hepatic proteins significantly decreased (P < 0.01) in high dose-treated animals (50 and 100 mg/kg) compared with controls. The number of implantation sites and the fertility rate were significantly lower (P < 0.05), while the antifertility activity increased significantly (P < 0.05) in treated rats compared with controls. When administered from the 1st to the 5th day of pregnancy, AEDv led to a decrease of more than 60% in the implantation rate in high dose-treated rats (50, 100, and 400 mg/kg). From the 6th to the 9th day, the implantation, gestation rates and the number of fetuses decreased significantly in all treated groups. From the 11th to the 20th day, a 50% resorption and decrease in gestation rate were reported in 50 mg/kg dose-treated animals. AEDv possesses weak contraceptive and abortifacient effects during pregnancy.


1971 ◽  
Vol 50 (4) ◽  
pp. 679-683 ◽  
Author(s):  
R. COLLU ◽  
F. FRASCHINI ◽  
L. MARTINI

SUMMARY Melatonin and 5-methoxytryptophol, the two methoxyindoles of pineal origin, were injected into a lateral ventricle of the brain of immature female rats. Treatment was started on the 25th day of age and terminated when the vagina opened. The injection of both methoxyindoles resulted in a statistically significant delay in vaginal opening. Since previous experiments had shown that melatonin specifically inhibits secretion of luteinizing hormone and that 5-methoxytryptophol specifically blocks release of follicle-stimulating hormone, the present results support the hypothesis that the onset of sexual maturation needs a balanced secretion of both gonadotrophins.


1954 ◽  
Vol 11 (4) ◽  
pp. 359-376 ◽  
Author(s):  
ANITA M. MANDL

SUMMARY The sensitivity of adrenalectomized, control-operated and unoperated rats to pregnant mare serum (PMS) and chorionic gonadotrophin (CG) has been studied. A total of 638 mature and immature female rats was used. The ovaries of adrenalectomized rats were found to contain fewer large follicles and corpora lutea than those of control-operated litter-mates, and the slight ovarian hypertrophy which occurs after surgical trauma was found to be due to an increase in the number of Graafian follicles and corpora lutea. Further experiment showed that, as judged by the weight of the ovaries, adrenalectomy reduces the ovarian reaction to injected PMS (10 i.u./day) in both adult and immature rats. Replacement therapy with DCA (1 mg/day) failed to re-establish the normal response in adults. Treatment with cortisone (1 mg/day) restored the normal reaction in both adult and immature adrenalectomized rats. Adrenalectomized adult rats responded to injected CG (10 i.u./day) as vigorously as their operated and unoperated litter-mates. On the other hand, immature adrenalectomized animals did not respond fully to CG. Treatment with cortisone again fully restored the normal reaction.


2002 ◽  
Vol 173 (2) ◽  
pp. 297-304 ◽  
Author(s):  
MJ Engelbregt ◽  
MM van Weissenbruch ◽  
C Popp-Snijders ◽  
HA Delemarre-van de Waal

In the present study we examined the consequences of intrauterine growth retardation and postnatal food restriction on the maturational process of sexual development by studying onset of first cycle. In addition, we investigated the effect of pregnant mare serum gonadotropin (PMSG) on ovarian growth and ovulation in intrauterine growth-retarded (IUGR) and postnatally food-restricted (PFR) rats. Intrauterine growth retardation was induced by uterine artery ligation on day 17 of gestation and food restriction was achieved by enlarging the litter to 20 pups per mother from day 2 after birth until weaning (day 24). In control rats, vaginal opening and the first cycle took place on the same day. In IUGR rats, uncoupling occurred between vaginal opening and the first cycle. Vaginal opening was delayed (P<0.05) and the first cycle was even further delayed (P<0.01) compared with controls. Body weight in IUGR rats was lower (P<0.05) at vaginal opening, but at first cycle and after stimulation with 50 IU PMSG in the first cycle it was similar to that in controls. In the ovaries of IUGR rats, the numbers of primordial (P<0.05), growing (P<0.01) and antral follicles (P<0.01), and the total number of follicles (P<0.01) were lower than in controls after stimulation with 50 IU PMSG at first cycle. The number of corpora lutea in the ovaries of the IUGR rats and the controls was similar and reflected superovulation. In the PFR rats, vaginal opening occurred at the same time as in control rats, but at a lower body weight (P<0.01). First cycle was much delayed (P<0.01), by which time body weight was greater (P<0.01) than that of controls at first cycle. On the basis of the differences in weight and age between PFR rats and controls at first cycle, we performed two studies. In study A, ovaries were analysed histologically 42 h after stimulation with PMSG at first cycle of control rats and age-matched PFR rats. In study B, the ovaries of PFR rats at first cycle and age-matched control rats were examined 42 h after PMSG stimulation. In the ovaries of the PFR rats in study A, a greater total number of follicles (P<0.05) was observed, represented by a greater number of primordial follicles (P<0.01) and a lower number of antral follicles (P<0.05), including corpora lutea. The number of corpora lutea in the ovaries of the PFR rats was significantly lower than that in controls (P<0.01). The total number of follicles in the ovaries of the PFR rats of study B did not differ from the age-matched controls after PMSG stimulation at first cycle, and neither did the number of the follicles in the different classes. We conclude that, in IUGR rats at first cycle, PMSG can induce multiple follicular growth and development followed by superovulation comparable to that in controls, despite a decreased total number of follicles in the ovaries. However, in PFR rats of the same age, the ovary is not capable of responding adequately to PMSG, despite a greater total number of follicles. Stimulation with PMSG at first cycle resulted in follicular growth and superovulation comparable to those in age-matched controls. Undernutrition in different critical time periods around birth in the rat leads to ovarian development in such a way that, in both groups, an increased risk of reduced reproductive capacity can be expected.


1980 ◽  
Vol 85 (2) ◽  
pp. 307-315 ◽  
Author(s):  
M. S. BLANK ◽  
A. E. PANERAI ◽  
H. G. FRIESEN

The effects of subcutaneous injections of the opiate antagonist naloxone on the tonic and phasic secretion of prolactin and LH were studied in rats. During development, resting levels of prolactin in serum were decreased by naloxone (2·5 mg/kg body wt) on days 24,45 and 50 in female rats and on days 28,45 and 50 in male rats. In the adult, naloxone (2·5 mg/kg body wt) decreased basal levels of serum prolactin in male rats and levels during oestrus in female rats. In 25-day-old female rats, serum LH rose from resting levels within 7·5 min of naloxone administration (2·5 mg/kg body wt) and returned to pretreatment levels by 30 min, while prolactin fell by 7·5 min and remained low for as long as 60 min after treatment. Furthermore, a tenfold lower dose of naloxone (0·25 mg/kg body wt) did not raise basal levels of serum LH but still decreased resting levels of serum prolactin in immature female rats (24 days old). The effect of naloxone (2·5 mg/kg body wt) on phasic LH release was studied in 29-day-old immature female rats primed on day 27 with pregnant mare serum gonadotrophin (PMSG). In these PMSG-treated rats the onset of the prolactin surge was blunted by naloxone while it had no effect on phasic LH release. Naloxone (5 mg/kg body wt) also induced a rise in levels of serum LH in ovariectomized rats and, if administered with morphine, it reversed the short-term inhibition of LH secretion caused by morphine. However, naloxone was ineffective after pretreatment with oestradiol benzoate. These findings suggest that the responses of serum LH and prolactin to naloxone were dissociated and that oestrogens and opiate peptides may have interacted to regulate secretion of LH.


1981 ◽  
Vol 241 (6) ◽  
pp. E460-E464
Author(s):  
J. R. Lorenzen ◽  
J. A. Ramaley

Serum gonadotropin levels were measured 12, 24, and 48 h after gonadectomy in male and female rats (ages, 22--60 days) to assess when during development the rate of rise of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after castration approximates that seen in the gonadectomized adult. In females serum LH levels 48 h after ovariectomy were increased above sham levels only when the ovaries were removed prior to vaginal opening. Ovariectomy on the day of vaginal opening or at older ages resulted in no increase in LH levels by 48 h after surgery. Serum FSH levels at 24 and 48 h after ovariectomy declined with increasing age at the time of ovariectomy. In males serum LH levels at 48 h after castration increased with increasing age at the time of gonadectomy. Serum FSH levels at either 12, 24, or 48 h after orchidectomy did not change appreciably with age at the time of surgery. It is concluded that the acute pituitary secretion of gonadotropins after removal of testes in the immature male resembles that seen in the mature male early in the course of the development of sexual maturity. In contrast, the acute pituitary secretion of gonadotropins after removal of the ovaries in the immature female does not resemble that seen in the ovariectomized adult until she is mature and capable of ovulating. Thus, the observed delay in the rise of LH seen in ovariectomized adults may be a function of some aspect of the hormonal changes associated with the estrous cycle.


1965 ◽  
Vol 49 (2) ◽  
pp. 239-247 ◽  
Author(s):  
T. Swelheim

ABSTRACT In adult female rats an ICSH-peak in the serum was found in the afternoon of pro-oestrus (preliminary experiments). ICSH was determined by the ventral prostate assay. Comparative ICSH-determinations were carried out in the serum of adult gonadectomized male and female rats with an ovarian transplant. Gonadectomy and transplantation of an ovary into the right hind-leg had been carried out two months previously. Irrespective as to whether there were corpora lutea in the transplants of castrated males, the ICSH-level in the serum of the males did not differ from the base level in the serum of the females. The ICSH-peak in the serum of the females (afternoon of pro-oestrus) exceeded this level. The relation between the ICSH-peak in the serum and ovulation was demonstrated by the fact that there was no ICSH-peak on the day of prooestrus in spayed females with an ovarian transplant, which in previous cycles had passed through a two days' oestrus. It is suggested that the difference in behaviour between ovarian transplants in spayed females and castrated males might be an expression of the same sex difference as that which appears in response to a single high dose of oestrogen.


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