RETARDATION OF FIRST OVULATION IN PUBERTAL RATS AFTER TREATMENT WITH 5α-ANDROSTANE-3α,17β-DIOL OR ITS 3β-EPIMER

1982 ◽  
Vol 92 (1) ◽  
pp. 31-35 ◽  
Author(s):  
P. KRAMER ◽  
H. M. A. MEIJS-ROELOFS

The effect was studied of five daily injections of 50 μg of either 5α-androstane-3α,17β-diol (3α-androstanediol) or its 3β-epimer (3β-androstanediol), starting on day 22 of life, on sexual maturation in female rats. No difference was found in the age and body weight at first oestrus between oil-treated rats and rats treated with either 3α- or 3β-androstanediol. The only difference observed between these groups consisted of the occurrence of a 'pinhole' vaginal opening a few days before oestrus in 50% of the steroid-treated rats; in oil-treated rats immediate full vaginal opening and first oestrus coincided in ten out of 12 rats. Different effects were obtained when the higher dose of 100 μg daily was used; effects were dissimilar in rats treated with 3α- and 3β-androstanediol. If administration of the higher dose of 3β-androstanediol was started on day 22 and continued until the day of full vaginal opening and first oestrus, a significant delay of this first oestrus, preceded by a few days of a 'pinhole' type of vaginal opening, was observed. After administration of the higher dose of 3α-androstanediol a 'pinhole' type of vaginal opening, accompanied by dioestrous-like vaginal smears, was also found, but oestrus did not occur during the period when injections were given. After the injections were stopped on day 45, first oestrus developed within 6 days in all rats. The previous findings of others that administration of 3β-androstanediol to the immature female rat may induce precocious puberty (i.e. precocious vaginal opening and first ovulation) were not confirmed in the present study. Our results indicate that high doses of free 3α-androstanediol, and to a lesser degree 3β-androstanediol, may even delay first ovulation in the rat. A possible interference of 3α-androstanediol with the triggering of the first ovulatory gonadotrophin peaks is discussed.

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.


1960 ◽  
Vol XXXIII (IV) ◽  
pp. 569-576 ◽  
Author(s):  
Ronald J. Gellert ◽  
William F. Ganong

ABSTRACT Eight female rats with electrolytic lesions involving the arcuate nucleus in the posterior tuberal region of the hypothalamus matured significantly earlier than unoperated controls. Lesions placed in the anterior hypothalamus, mammillary body, hippocampus, cortex and thalamus of immature female rats had no effect on the age at which vaginal opening and first oestrus occurred.


1976 ◽  
Vol 71 (3) ◽  
pp. 299-304 ◽  
Author(s):  
RIVKA RAVID ◽  
BENJAMIN ECKSTEIN

SUMMARY The conjugation of 5α-androstane-3α,17β-diol (3α-A) and its 3β epimer (3β-A) was determined in the peripheral blood of immature female rats. About two thirds of these steroids were present in blood as sulphates and one third as glucuronides; no free steroids were detected. Administration of 3β-A sulphate (25 μg/100 g body weight/day) and of 3α-A sulphate (50 μg/100 g/day) from day 21 of life until the day of vaginal opening, advanced the day of the first ovulation. Administration of the 3β-A sulphate did not induce precocious vaginal opening whereas the free alcohol was active in this respect. Implantation of 3β-A sulphate, but not of the 3α epimer, into the basal medial hypothalamus resulted in the death of all animals within 24 h.


2010 ◽  
Vol 22 (1) ◽  
pp. 279
Author(s):  
S. H. Hyun ◽  
E. B. Jeung

In this study, to examine the estrogenic activity effects of parabens on hormonal responsiveness and on change in the morphology of reproductive target tissues during a critical development stage in female rats, analyses for parabens including methyl-, ethyl-, propyl-, isopropyl-, butyl-, and isobutylparaben were performed in an immature female Sprague-Dawley rat model. Two hundred female immature rats (n = 10/group) were orally treated with these parabens from postnatal day 21 to 40 in a dose-dependent manner based on our previous study [62.5, 250, and 1000 mg/kg of body weight (BW) per day]. 17α-ethinylestradiol (EE;1 mg/kg of BWper day) was used as a positive control and corn oil as a vehicle.A high doseofmethyl- and isopropylparaben (1000 mg/kg of BW per day) resulted in a significant delay in the date of vaginal opening and a decrease in length of the estrous cycle (P < 0.05). In measurements of organ weight and body weight, we observed significant weight changes in ovaries, adrenal glands, thyroid glands, liver, and kidneys(P < 0.05); conversely, body weight was not altered following paraben treatment. In all groups exposedto paraben treatment, histological analysis of the ovaries from the immature rats revealed interstitial cell disorders, a lack of corpora lutea, an increase in the number of cystic follicles, and thinning of the follicular epithelium, which occurred in a dose-dependent manner. In addition, morphological studies of the uterus revealed the myometrial dysplasia suchas myometrial hyperplasia inthe high-doseofpropyl- and isopropylparaben (1000 mg/kgof BWper day) group and in all dose of butyl- and isobutylparabens groups. We also observed a significant decrease in serum estradiol and T4 concentrations in methyl-, ethyl-, propyl-, isopropyl-, and isobutylparaben-treated groups (P < 0.01 and 0.05).A receptor-binding assay indicated that the relative binding affini- ties of parabens to estrogen receptors occurred in the order: isobutylparaben > butylparaben > isopropylparaben = propylparaben > ethylparaben. These values were much less than the binding affinity for 17?-estradiol. Taken together, long-term exposure to parabens, which show less estrogenic activity than EEl, can produce suppressive effects on hormonal responsiveness and can disrupt the morphology of reproductive target tissues during this critical stage of development in immature female rats.


1985 ◽  
Vol 104 (2) ◽  
pp. 299-307 ◽  
Author(s):  
D. J. S. Sirinathsinghji ◽  
M. Motta ◽  
L. Martini

ABSTRACT Studies were undertaken using the opiate receptor antagonist naloxone to examine the hypothesis that endogenous opiates may have a restraining effect on prepubertal gonadotrophin secretion and may be involved in the maturation of the central nervous system mechanisms regulating the onset of puberty in the female rat. Naloxone (2·5 mg/kg) administered intraperitoneally every 6 h to female rats from day 1 to day 10 of postnatal life significantly (P <0·001) advanced the age of onset of puberty assessed in terms of the day of vaginal opening and first oestrus (32·3 ± 0·2 vs 40·8 ± 0·4 days in control saline-treated animals). Animals so treated with naloxone showed significantly (P < 0·001) higher levels of FSH (761·4 ± 87·6 vs 483·8± 57·2 μg/l in control animals) and LH (562·8 ± 57·4 vs 351·3 ± 43·3 μg/l in control animals) at the first late pro-oestrus and a significantly (P < 0·001) higher number of ova released at first oestrus (12·4 ± 0·4 vs 8·1±0·3 in controls). Body weight at first oestrus was significantly (P <0·001) lower in the naloxone-treated animals, an indication that these animals were much younger. The weights (per 100 g body wt) of the ovaries and uteri at the first oestrus were significantly (P <0·01) higher in the naloxone-treated rats than in the controls. However, there were no significant differences in the weights of the adrenals and anterior pituitary glands between the two groups of animals. A study of the cyclic patterns of the neonatally naloxone-treated animals performed for 15 consecutive cycles after the first oestrus showed normal 4- or 5-day cycles similar to those occurring in the saline-treated animals. The lengths of the first and second cycles in the naloxone-treated animals were not significantly different from controls. No significant differences in body weight or in organ weights at oestrus or in the levels of LH and FSH determined during the various stages of the oestrous cycle were found between naloxone- and saline-treated animals when these parameters were examined at 3 months of age. Naloxone had no effect on onset of puberty when administered during the other stages of prepubertal life. The mechanisms by which naloxone acts specifically during the neonatal period to induce precocious puberty are at present not known but are being investigated; they may be related to naloxone-induced alterations in the inhibitory synaptic arrangements between opiatergic and gonadotrophin-releasing hormone (GnRH) neurones, with a resulting decrease in the inhibitory influence exerted by endogenous opioids on GnRH neurones during this period of intense neurological development. The results suggest that the endogenous opiate peptides could play a key role in the central mechanisms which trigger the onset of puberty in the female rat. J. Endocr. (1985) 104, 299–307


Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 1740-1750 ◽  
Author(s):  
Delphine Franssen ◽  
Arlette Gérard ◽  
Benoit Hennuy ◽  
Anne-Françoise Donneau ◽  
Jean-Pierre Bourguignon ◽  
...  

Abstract Rat sexual maturation is preceded by a reduction of the interpulse interval (IPI) of GnRH neurosecretion. This work aims at studying disruption of that neuroendocrine event in females after early exposure to a very low dose of bisphenol A (BPA), a ubiquitous endocrine disrupting chemical. Female rats were exposed to vehicle or BPA 25 ng/kg·d, 25 μg/kg·d, or 5 mg/kg·d from postnatal day (PND)1 to PND5 or PND15. Exposure to 25 ng/kg·d of BPA for 5 or 15 days was followed by a delay in developmental reduction of GnRH IPI studied ex vivo on PND20. After 15 days of exposure to that low dose of BPA, vaginal opening tended to be delayed. In contrast, exposure to BPA 5 mg/kg·d for 15 days resulted in a premature reduction in GnRH IPI and a trend toward early vaginal opening. RNA sequencing analysis on PND20 indicated that exposure to BPA resulted in opposing dose effects on the mRNA expression of hypothalamic genes involved in gamma aminobutyric acid A (GABAA) neurotransmission. The study of GnRH secretion in vitro in the presence of GABAA receptor agonist/antagonist confirmed an increased or a reduced GABAergic tone after in vivo exposure to the very low or the high dose of BPA, respectively. Overall, we show for the first time that neonatal exposure to BPA leads to opposing dose-dependent effects on the neuroendocrine control of puberty in the female rat. A very low and environmentally relevant dose of BPA delays neuroendocrine maturation related to puberty through increased inhibitory GABAergic neurotransmission.


1977 ◽  
Vol 74 (1) ◽  
pp. 11-21 ◽  
Author(s):  
M. WILKINSON ◽  
D. DE ZIEGLER ◽  
DANIELLE CASSARD ◽  
K. B. RUF

The effects of oestrogen priming on the sensitivity of the anterior pituitary gland to stimulation with gonadotrophin releasing hormone (GnRH) was investigated in immature female rats using a new organ culture technique. Hemipituitary glands obtained from animals primed with a single dose of oestradiol benzoate (OB; 20 μg/100 g body weight) released significantly more LH when pulsed with GnRH (4 nmol/l) than did control hemipituitary glands. This potentiating effect was detectable as early as 5 days after birth. After a second stimulation, LH secretion remained high. These results were compared with those obtained from animals treated to induce increased levels of endogenous oestrogen on day 26 of life. Thus, hemipituitary glands were obtained from animals given two injections of OB, an injection of pregnant mare serum gonadotrophin (PMSG) or a unilateral brain lesion placed in the basal hypothalamus. Pituitary tissue was stimulated as before with a pulse of GnRH. Two injections of OB enhanced the sensitivity to stimulation. Conversely, both PMSG and lesion treatment severely reduced the sensitivity to GnRH, although PMSG-treated and lesioned animals have been used as models for the study of ovulation.


1979 ◽  
Vol 13 (3) ◽  
pp. 283-286 ◽  
Author(s):  
M. L. Norris ◽  
C. E. Adams

Summary Keeping a sexually mature male with a weanling female rat advanced neither the time of vaginal opening nor that of 1st oestrus. In 2 of 3 experiments females kept singly after weaning reached sexual maturity significantly earlier than did grouped females. The reproductive performance of females mated at 1st oestrus was not significantly different from that of older primiparae. 26 rats gave birth to an average of 9·3 young at 59·5 days of age, and 22 of them reared 96% of the young to weaning.


2019 ◽  
Vol 9 (6-s) ◽  
pp. 119-126
Author(s):  
Mataphouet Emmanuel AFFY ◽  
Wahon Marie-Odile TOVI ◽  
N’guessan Ernest ZOUGROU ◽  
Koffi KOUAKOU

Objective : The aim of this study is to determine the pharmacological effects and the estrogenic properties of Amaranthus viridis leaves on the reproductive function of animal model (female rat). Methods : Vaginal smears performed 9 days before treatment allowed to select female rats having alternated on two cycles a regularity. Thereafter, the selected rats were administered by gavage daily for 28 days taking care of smear every morning at 7am from the first day of treatment follow the evolution of the cycle. For this study 20 nulliparous rats, 2 months old, weighing between 120-150 g. The first group (control) was administered with olive oil and the other three batches received respectively the doses 200, 400 and 600 mg/kg of the methanolic extract of Amaranthus viridis. At the end of the 28-day treatment, ovary and uterine horn were removed, histological and hormonal parameters were studied for determine pharmacological effects of methanolic extract of Amaranthus viridis. Results : The extract caused a disturbances of the cycle according to the doses administered. Disturbances at doses 200 and 400 mg/kg PC are significant. The calculation of the total duration of the different phases of the cycle revealed very significant increases in the estrous phase (P<0.01) by 22.79 % and 17.13 % at the respective doses of 200 and 400 mg/kg b.w compared to control. Non-significant difference was recorded on FSH, LH and estradiol level. On progesterone level, administration of the methanolic extract showed a significant difference at dose of 600 mg/kg b.w compared to control. On histological structure of the ovary, the presence of active and degenerate corpus luteum, secondary follicles depending on the dose administered were recored. Conclusion : The results showed that the methanolic extract of Amaranthus viridis contain estrogenic substances or estrogen-like substances according to a dose-dependent mechanism, with high estrogenic potential at doses of 200 and 400 mg/kg b.w . Keywords: vaginal smears, Amaranthus viridis, methanolic extract, histology


2002 ◽  
Vol 172 (3) ◽  
pp. 441-448 ◽  
Author(s):  
L Pinilla ◽  
ML Barreiro ◽  
LC Gonzalez ◽  
M Tena-Sempere ◽  
E Aguilar

Hypothalamic differentiation in the female rat during the neonatal period is critically dependent on the steroid milieu, as permanent changes in reproductive function are observed after administration of oestradiol and testosterone during such a critical stage. Selective oestrogen modulators (SERMs) constitute a family of drugs that, depending on the tissue, are able to exert oestrogenic or antioestrogenic actions. The present experiments were conducted to analyse whether the SERMs, tamoxifen and raloxifene, can cause oestrogenic actions during the hypothalamic differentiation period. Postnatal female rats were injected between days 1 and 5 with 100 microg/day tamoxifen, raloxifene or ICI 182,780 (a pure antioestrogen). Other groups of animals were injected on day 1 of age with 100 microg oestradiol benzoate (OeB) or 1.25 mg testosterone propionate (TP) alone or in combination with raloxifene (500 microg/day between days 1 and 5). In all experimental groups, the age, body weight and concentrations of serum gonadotrophins at vaginal opening were recorded, whereas vaginal cyclicity and the negative and positive feedback between oestradiol and LH were monitored in adulthood. The results obtained confirmed the ability of high doses of OeB or TP to alter the normal differentiation of the brain permanently. They also reinforced the hypothesis that oestrogens are also necessary for normal brain differentiation in female rats because administration of a pure antioestrogen, such as ICI 182,780 permanently altered the function of the reproductive axis. In addition, our data provided evidence for different actions of the two SERMs under analysis (raloxifene and tamoxifen) upon peripheral targets, as raloxifene advanced vaginal opening whereas tamoxifen did not. In contrast, their actions on brain differentiation appeared similar and analogous to those obtained after neonatal administration of oestradiol, as evidenced by vaginal acyclicity, ovarian atrophy, sterility and abolition of negative and positive feedback between oestradiol and LH, thus suggesting an oestrogenic action of these SERMs on hypothalamic differentiation. Moreover, the oestrogenic activity of raloxifene was supported by its inability to block the effects of OeB and TP administered neonatally. In conclusion, the present results indicated that the SERMs, tamoxifen and raloxifene, exert an oestrogen-like effect upon hypothalamic differentiation of the neonatal female rat.


Sign in / Sign up

Export Citation Format

Share Document