INCREASED PRODUCTION OF FOLLICLE-STIMULATING HORMONE IN IMMATURE FEMALE RATS BY A SINGLE INJECTION OF ANDROGEN OR OESTROGEN

1969 ◽  
Vol 45 (1) ◽  
pp. 29-36 ◽  
Author(s):  
R. H. NAQVI ◽  
D. C. JOHNSON

SUMMARY An increase in ovarian weight in immature rats after the injection of chorionic gonadotrophin (HCG) was used to measure variations in endogenous follicle-stimulating hormone (FSH) after steroid treatment. A single injection of several steroids (testosterone, androstenediol, androstenedione, oestradiol benzoate) given 12–96 hr. before treatment with HCG caused a 30–200% increase in ovarian weight. This was not a direct effect of the steroids since hypophysectomy abolished the response, and administration of the compounds concurrently with HCG was ineffective. Within certain limits an increase in the duration of pretreatment enhanced the ovarian response while an increase in the dose of steroid had little effect. Pretreatment with testosterone propionate did not change pituitary FSH activity, indicating that the increase in circulating FSH was due to an increased production of hormone. On the other hand, pituitary FSH in animals treated with oestradiol benzoate was significantly lowered within 72 hr. suggesting an increased release of FSH.

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.


1972 ◽  
Vol 54 (2) ◽  
pp. 277-284 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS

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.


1973 ◽  
Vol 59 (2) ◽  
pp. 295-304 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
J. Th. J. UILENBROEK ◽  
F. H. de JONG ◽  
R. WELSCHEN

SUMMARY Oestradiol-17β (E2) was measured by radioimmunoassay in the plasma of immature female rats. Maximal E2 levels of 55–60 pg/ml were found at 10–15 days of age; from day 25 to day 35 E2 levels were low to undetectable. The E2 measured appeared to be of ovarian origin: ovariectomy performed on day 13 resulted in a decreased E2 level 2 days later (13 pg/ml) as compared with the value from the control litter mates (46 pg/ml); after adrenalectomy the level of circulating E2 remained normal (54 pg/ml). The effects of ovariectomy and adrenalectomy on uterine weights followed a similar pattern: ovariectomy resulted in a decrease and adrenalectomy in no change in uterine weight. In the strain of rat used, levels of follicle-stimulating hormone (FSH) in the serum (measured by radioimmunoassay) were high from day 10 to day 20 and showed a steep decrease on day 21. After ovariectomy on day 15 this decrease in serum FSH was not observed. The influence of circulating E2 on serum levels of FSH was studied after ovariectomy followed by treatment with varying doses of oestradiol benzoate. Ovariectomy on day 13 resulted in a significantly increased FSH level 2 days later (1770 ng NIAMD-rat-FSH RP-1/ml) as compared with the value obtained from control animals (1033 ng/ml). This increase was not observed after daily injections of 0·1 μg oestradiol benzoate/100 g body weight. The results indicate that E2 and FSH concentrations show a similar pattern between 5 and 35 days of age. Furthermore, an inhibitory feedback mechanism between oestrogens and FSH concentrations was found to be operative. The implications of these findings are 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.


1970 ◽  
Vol 63 (3) ◽  
pp. 454-475 ◽  
Author(s):  
P. Petrusz ◽  
C. Robyn ◽  
E. Diczfalusy

ABSTRACT The biological effects of human follicle stimulating hormone (FSH) preparations were studied in intact immature female mice and in hypophysectomized immature female and male rats, following the complete neutralization of the luteinizing hormone (LH) content of human urinary menopausal gonadotrophin (HMG) preparations having – prior to neutralization – FSH:LH ratios ranging between 1.0 and 500.0. Neutralization of LH was achieved by the addition of rabbit anti-human chorionic gonadotrophin (HCG) sera of known anti-LH potency. The amount of anti-LH employed was 1.5 to 730 times more than that required for 100% neutralization. In intact immature female mice, such »LH-free« FSH preparations induced an increased ovarian weight, follicle stimulation, as well as a uterine weight increase. In immature hypophysectomized female rats, »LH-free« FSH preparations induced ovarian weight increase, growth and maturation of the Graafian follicles without repair of the deficient interstitial cells and without any signs of luteinization. These ovarian changes were associated with an increase in uterine weight and with vaginal cornification. In view of these data, it is concluded that human urinary FSH per se is capable of inducing oestrogen synthesis in hypophysectomized female rats. In immature hypophysectomized male rats, »LH-free« FSH preparations induced testicular enlargement without any stimulation of the testicular interstitial cells and without any growth of the ventral prostate and seminal vesicles. The same effects were obtained following a prolonged administration (3 weeks); spermiogenesis was stimulated, but no mature spermatozoa were found.


1978 ◽  
Vol 78 (1) ◽  
pp. 31-38 ◽  
Author(s):  
G. VANDOREN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN ◽  
P. DE MOOR

Evidence is presented that the level of α2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats α2u-globulin cannot be detected. Moreover, α2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of α2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of α2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of α2u-globulin.


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.


1975 ◽  
Vol 64 (2) ◽  
pp. 329-336 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
W. J. DE GREEF ◽  
J.TH.J. UILENBROEK

SUMMARY In immature female rats, low values for concentrations of plasma progesterone were generally found from days 6–15 and from days 25–32 of life. Maximum progesterone concentrations (13·0–14·1 ng/ml), comparable to metoestrous values in the adult rat, occurred on days 20–22. The progesterone appeared to be of ovarian origin since after ovariectomy, on day 18, low progesterone concentrations were found 1 and 2 days later (2·5 ng/ml and 1·3 ng/ml) as compared with control values of 10·7 ng/ml and 14·1 ng/ml. However, adrenalectomy also lowered progesterone concentrations, 1 and 2 days later (6·4 and 4·9 ng/ml). The effect of progesterone, either alone or in combination with oestradiol benzoate (OB), on serum gonadotrophins was studied in rats ovariectomized on day 18. The highest dose of progesterone (0·15 mg) only slightly diminished the rise in serum luteinizing hormone (LH) after ovariectomy and had no effect on serum follicle-stimulating hormone (FSH). Oestradiol benzoate in a dose of 0·025 μg/100 g body weight was highly effective in preventing the rise in both LH and FSH concentrations, and OB treatment (resulting in a near-physiological oestradiol concentration) combined with progesterone treatment was more effective than treatment with OB alone. The results suggest that the amounts of progesterone and oestradiol present in the 20-day-old rat are adequate to cause the decrease in FSH level normally observed in immature female rats around this age.


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