242 POTENTIAL ESTROGENIC EFFECT(S) OF PARABENS AT THE NEONATAL STAGE OF AN IMMATURE FEMALE RAT MODEL

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.

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.


Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 210
Author(s):  
Sullim Lee ◽  
Geum Jin Kim ◽  
Hyukbean Kwon ◽  
Joo-Won Nam ◽  
Ji Yun Baek ◽  
...  

Menopause, caused by decreases in estrogen production, results in symptoms such as facial flushing, vaginal atrophy, and osteoporosis. Although hormone replacement therapy is utilized to treat menopausal symptoms, it is associated with a risk of breast cancer development. We aimed to evaluate the estrogenic activities of Spartina anglica (SA) and its compounds and identify potential candidates for the treatment of estrogen reduction without the risk of breast cancer. We evaluated the estrogenic and anti-proliferative effects of extracts of SA and its compounds in MCF-7 breast cancer cells. We performed an uterotrophic assay using an immature female rat model. Among extracts of SA, belowground part (SA-bg-E50) had potent estrogenic activity. In the immature female rat model, the administration of SA-bg-E50 increased uterine weight compared with that in the normal group. Among the compounds isolated from SA, 1,3-di-O-trans-feruloyl-(-)-quinic acid (1) had significant estrogenic activity and induced phosphorylation at serine residues of estrogen receptor (ER)α. All extracts and compounds from SA did not increase MCF-7 cell proliferation. Compound 1 is expected to act as an ERα ligand and have estrogenic effects, without side effects, such as breast cancer development.


1995 ◽  
Vol 145 (3) ◽  
pp. 409-416 ◽  
Author(s):  
D Sömjen ◽  
Y Amir-Zaltsman ◽  
B Gayer ◽  
G Mor ◽  
N Jaccard ◽  
...  

Abstract Previous studies indicated that the anti-idiotypic antibody (clone 1D5) caused an increase in uterine creatine kinase (CK) activity when administered in vivo to immature female rats, indicating that the antibody has oestrogenic-like activity. It was, therefore, of interest to investigate the structural requirements of clone 1D5 to act as an oestrogen mimetic in an in vitro model system. In the present study, the effect of clone 1D5 and its proteolytic fragments, F(ab′)2, Fab′ and Fc on CK activity was examined in cultured skeletal cells having functional oestrogen receptor (ER). Incubation of female-derived calvaria cells or epiphyseal cartilage cells with clone 1D5 (8·33 nm) or oestradiol (E2) (30 nm) for 24 h caused a significant increase in CK activity, indicating that clone 1D5 acted as an agonist. On the other hand, incubation of male-derived calvaria cells devoid of a functional ER with clone 1D5 or E2 did not have any effect on CK activity. Incubation of female-derived calvaria cells with clone 1D5 and E2 did not result in any further increase in CK activity, whereas dihydrotestosterone (DHT) did not alter the response to clone 1D5. The CK response to clone 1D5, in female-derived calvaria cells was time- and dose-dependent and could be inhibited in a dose-dependent manner by the oestrogen antagonist tamoxifen. In contrast, the proteolytic fragments of clone 1D5, the F(ab′)2 dimer (12 nm) and the Fab′ monomer (24 nm), and the Fc fragment (28 nm) did not have E2-like activity in these cells. However, while the Fab′ monomer or the Fc fragment, as well as clone 1D5, did not affect the response of the female-derived calvaria cells to E2, the F(ab′)2 dimer acted like an antagonist and completely inhibited the stimulatory effect of E2 or 1D5, but was unable to block the stimulatory effect of DHT on CK in male-derived calvaria cells. Collectively, these results imply that a bivalent antibody is necessary for the observed physiological responses, and that the anti-idiotypic antibody can be converted from an agonist to an antagonist by removal of the Fc portion of the antibody molecule. Furthermore, the anti-idiotypic antibody has an oestrogenic-like effect inhibited by tamoxifen only in skeletal cells capable of responding to E2. Journal of Endocrinology (1995) 145, 409–416


1989 ◽  
Vol 8 (2) ◽  
pp. 377-404 ◽  
Author(s):  
Joseph F. Borzelleca ◽  
Elizabeth C. Clarke ◽  
L. W. Condie

Male and female Sprague-Dawley-derived rats received CdCl2 by gavage at doses of 25, 51, 107, and 225 mg CdCl2 per kg body weight per day for 1 or 10 consecutive days or in drinking solutions at concentrations of 13–323 mg CdCl2 per liter for 10 consecutive days. There were appropriate controls. In the 1 day study in males only, an apparent treatment-related but not statistically significant decrease in body weight was reported; spleen weights and ratios were significantly lower and lung weights and ratios were significantly higher (in the highest dose only). Dose-dependent mortality was observed in the 10 day gavage study. Body weight gain was depressed in a dose-dependent manner in both males and females. Weights and/or ratios of brain, liver, spleen, lungs, thymus, kidneys, and testes of treated males were depressed in a dose-dependent manner. In females, weights and/or ratios of liver, spleen, thymus, and kidneys were depressed in a dose-dependent manner. Focal necrotic changes in renal tubular epithelium and tubular degeneration were reported in males and females. Testicular and hepatic histopathologic changes (testicular atrophy and necrosis and hepatic necrosis) were also reported in males. In the drinking water study, males demonstrated dose-dependent decreases in body weight gain and weight and/or ratios of liver, spleen, thymus, and kidneys. There were no significant compound-related effects in females, although liver weights and ratios were lower. There were no compound-related histopathologic effects.


1961 ◽  
Vol 39 (5) ◽  
pp. 961-965 ◽  
Author(s):  
L. Goodfriend ◽  
A. H. Sehon

It was demonstrated that (i) antiserum to estrone-17-carbamido-HSA neutralized the 6-hour uterotropic activity of exogenous estrone in immature rats, and (ii) the estrone-17-carbamido-proteins were devoid of estrogenic activity at the 5.0-mg dosage level in immature female rats.


1988 ◽  
Vol 119 (2) ◽  
pp. 185-189 ◽  
Author(s):  
R. S. Carson ◽  
J. W. McMaster

ABSTRACT The effect of exogenous ovine gonadotrophins on ovarian inhibin content in hypophysectomized immature female rats was studied to determine which of the pituitary gonadotrophins control ovarian inhibin production in vivo. Inhibin and steroid contents of 27 000 g ovarian supernatants were measured by specific radioimmunoassay. Whereas injection of ovine (o)FSH resulted in dose-dependent increases in ovarian weight, progesterone and oestradiol content above that of control animals injected with diethylstilbestrol alone, injection of oLH was without significant effect. Similarly, ovarian inhibin content was not altered significantly by injection of oLH, but was increased in a dose-dependent manner by injection of oFSH. Concentrations of inhibin in serum were correlated directly with ovarian inhibin content. The results of this study indicate that ovarian inhibin content is increased by injection of oFSH but not oLH. It is likely, therefore, that inhibin production by small antral follicles is controlled by FSH activity alone. J. Endocr. (1988) 119, 185–189


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.


Author(s):  
Dao Thi Vui ◽  
Nguyen Thu Hang ◽  
Nguyen Quoc Huy ◽  
Bui Thanh Tung

Background: Pueraria candollei variety mirifica (PM) has been widely used as ingredient in many rejuvenating products. In this study, we aimed to assess the estrogenic activity of PM extract grown in Vietnam.Methods: Estrogenic activity of PM extract was estimated on immature female rats by using uterotrophic method to measure the weight of the reproductive organs. Estrogenic activity of PM extract also was investigated in mature female ovariectomized rats by evaluating the vaginal cells growth, reproductive organs weight, serum estradiol concentration.Results: Our results showed that PM extract at doses of 100 mg/kg, 200 mg/kg had increased the reproductive organs weight in immature rats and female ovariectomized rats. In addition, PM extract had increased the serum estradiol concentration and the vaginal cells growth by increasing the percentage of keratinocytes in female ovariectomized rats.Conclusions: Our results showed that PM extract has strong estrogenic activity in rats.


1989 ◽  
Vol 256 (1) ◽  
pp. R276-R280 ◽  
Author(s):  
T. Gerardo-Gettens ◽  
B. J. Moore ◽  
J. S. Stern ◽  
B. A. Horwitz

Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin-treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding.


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.


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