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

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.

1988 ◽  
Vol 116 (1) ◽  
pp. 43-53 ◽  
Author(s):  
M. Laudon ◽  
Z. Yaron ◽  
N. Zisapel

ABSTRACT N-(3,5-dinitrophenyl)-5-methoxytryptamine (ML-23) has recently been synthesized and shown to antagonize the inhibitory effect of melatonin on the release of dopamine in vitro from the hypothalamus of female rats. In the present study the ability of ML-23 to inhibit in vivo the following melatonin-mediated effects was investigated: (1) delayed sexual maturation of young male rats, (2) delayed sexual maturation of young female rats, (3) inhibition of ovulation in mature female rats and (4) re-establishment of oestrous cycles in adult female rats maintained in continuous light. The inhibitory effect of daily melatonin injections, given in the afternoon, on the growth of the prostate gland and seminal vesicles and on serum testosterone concentrations in young male rats was prevented by daily injections of ML-23. Daily injections of ML-23 alone did not affect sexual maturation of young rats. In young male rats treated through the drinking water with melatonin, the growth of the accessory sex organs, but not that of the testes, was delayed and serum concentrations of testosterone were lower than in untreated rats. Administration of ML-23 through the drinking water increased serum concentrations of testosterone but did not significantly affect the weights of the accessory sex organs. Simultaneous administration of ML-23 and melatonin through the drinking water prevented completely, in a dose-dependent manner, the melatonin-mediated decrease in epididymal weights and in serum concentrations of testosterone and partially inhibited the delayed growth of the prostate glands and seminal vesicles. In young female rats treated with melatonin through the drinking water for 30 days, the growth of the ovaries was inhibited and serum concentrations of oestradiol were lower than in untreated rats. The growth of the uterus was not significantly affected. Administration of ML-23 through the drinking water did not significantly affect uterine and ovarian weights or oestradiol concentrations. Simultaneous administration of melatonin and ML-23 through the drinking water prevented completely the melatonin-mediated decrease in ovarian weights and in serum oestradiol concentrations. Ovulation during presumptive oestrus was prevented in adult female rats treated through the drinking water for 7 days with melatonin. Administration of ML-23 alone did not significantly affect the average numbers of ova shed and corpora lutea present. Simultaneous administration of ML-23 and melatonin prevented completely the melatonin-mediated inhibition of ovulation; the average number of ova shed was the same as in controls. Suppression of reproductive cycles occurred in adult female rats after long-term exposure to continuous light. This suppression was prevented by daily injections of melatonin in the afternoon; the incidence of constant oestrus decreased by 80%. Simultaneous injection of ML-23 and melatonin into rats maintained under continuous illumination prevented the effect of melatonin, and all the animals remained in constant oestrus. Administration of ML-23 alone did not alter the incidence of constant oestrus. A tritium-labelled derivative of ML-23 was prepared and administered orally to male rats. Peak concentrations of ML-23 occurred in the blood within 30 min after feeding and disappeared subsequently with a half-life of about 42 min. Intraperitoneal injection of [3H]ML-23 resulted in the appearance of peak concentrations of the drug in the brain within 20 min. The effects of ML-23 on serotonin S1 and S2 receptors, dopamine D2 receptors and melatonin receptors in the brain of the male rat were investigated using [3H]serotonin, [3H]spiperone and 2-[125I]iodomelatonin respectively. The binding of [3H]serotonin to brain synaptosomes and of [3H]spiperone to synaptosomes prepared from the cortical and caudate regions of the cerebrum was unaffected by ML-23 (10 μmol/l), whereas the binding of 2-[125I]iodomelatonin to brain synaptosomes was entirely inhibited. The results demonstrate the potency of ML-23 in antagonizing melatonin-mediated effects in the male and female rat in vivo. The drug may be administered to the animals simply through the drinking water, for relatively long periods without apparent deleterious effects on survival and welfare. ML-23 is accessible to both central and peripheral sites and acts specifically on melatonin but not on serotonin or dopamine receptors in the brain. The availability of a melatonin antagonist offers new opportunities for exploring the physiological role of melatonin in the neuroendocrine system. J. Endocr. (1988) 116, 43–53


1985 ◽  
Vol 106 (1) ◽  
pp. 61-66 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
P. Osman

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


1965 ◽  
Vol 33 (3) ◽  
pp. 447-454
Author(s):  
M. J. K. HARPER

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jodi L. Pawluski ◽  
Eva van Donkelaar ◽  
Zipporah Abrams ◽  
Virginie Houbart ◽  
Marianne Fillet ◽  
...  

Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.


1983 ◽  
Vol 103 (3) ◽  
pp. 406-412 ◽  
Author(s):  
Kalle Jääkeläinen ◽  
Seppo Markkanen ◽  
Hannu Rajaniemi

Abstract. The subcellular distribution of 125I-labelled human chorionic gonadotrophin (hCG) in preovulatory rat granulosa cells was studied in vivo. Pregnant mare serum gonadotrophin-pretreated immature female rats received an iv injection of [125I]hCG a few hours before the endogenous preovulatory gonadotrophin surge. The animals were killed at 2 or 6 h after the [125I]hCG injections. Light microscope autoradiographs showed that the mural granulosa cells of large follicles were the most highly labelled cells in the ovaries. Electron microscope autoradiography was used to study the subcellular distribution of radioactivity in the mural granulosa cells. At 2 h 45% of the counted silver grains were associated with the plasma membrane and 10% with the lysosomes, at 6 h the values were 51% and 9%, respectively. The distribution of the observed silver grains was compared with the generated expected source to grain pairs by computerized linear multiple regression analysis. The magnitudes of the regression coefficients revealed that the plasma membrane and the lysosomes were the only specifically 125I-labelled organelles, that a few radioactive molecules were located diffusely over the cytoplasm at 2 h and that the 125I-radioactivity of the nuclei was negligible. The present results suggest that preovulatory rat granulosa cells are in vivo able to internalize into lysosomes [125I]hCG initially bound to LH/hCG receptors of the plasma membrane.


1971 ◽  
Vol 50 (2) ◽  
pp. 321-327 ◽  
Author(s):  
J. G. BAINBRIDGE ◽  
A. P. LABHSETWAR

SUMMARY In an attempt to locate the site(s) of action of the positive feedback of oestrogen for ovulation, a potent anti-oestrogen, I.C.I. 46474, was stereotaxically implanted into various parts of the brain or into the anterior pituitary. A dose of 5 μg of the anti-oestrogen when implanted into the cerebral cortex or injected subcutaneously on the morning of the day before pro-oestrus in 4-day cyclic rats was only marginally active in interfering with ovulation. By contrast, when the same amount was implanted into the median eminence region or the anterior pituitary, ovulation failed to occur in 80–100% of the rats (P < 0·05). Implantation of the cocoa butter vehicle alone into these regions interfered with ovulation in less than 35% of animals. Introduction of the anti-oestrogen into the anterior hypothalamic or mammillary region gave equivocal results. The data suggest that both the median eminence and the anterior pituitary contain receptors which can be blocked by the anti-oestrogen with resultant inhibition of ovulation. It is concluded that the positive feedback of oestrogen for ovulation is exerted both at the pituitary and the hypothalamic levels.


1985 ◽  
Vol 5 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Alison M. Crane ◽  
Louis Sokoloff

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.


1985 ◽  
Vol 106 (1) ◽  
pp. 31-NP ◽  
Author(s):  
G. Watanabe ◽  
K. Taya ◽  
S. Sasamoto

ABSTRACT The present study was undertaken to determine whether hypothalamic differentiation is involved in the selective release of FSH during the periovulatory period using adult male rats castrated and implanted with an ovary. Adult male rats (70–90 days old) were castrated and an ovary obtained from a prepubertal female rat (26 days old) was immediately grafted subcutaneously. Four weeks later, human chorionic gonadotrophin (hCG, 10 i.u.) was injected i.v. into the experimentally manipulated rats to induce ovulatory changes in the grafted ovaries. Another group of similarly prepared rats was injected with 0·9% (w/v) NaCl solution as controls. After injection of hCG, plasma concentrations of FSH increased significantly by 6 h, reached peak values at 12 h and declined to control levels at 36 h. On the other hand, plasma concentrations of LH were reduced by 6 h and decreased further during the next 36 h. An abrupt fall in plasma concentrations of oestradiol-17β occurred within 3 h of the administration of hCG. Histological examination revealed that ovulatory changes and luteinization of follicles were induced in grafted ovaries by 18 h after the injection of hCG. Thirty-six hours after treatment with hCG, a set of newly formed corpora lutea was observed in grafted ovaries and plasma concentrations of progesterone were raised. Treatment with oestradiol-17β did not inhibit the selective release of FSH after the administration of hCG, suggesting that the abrupt decrease in secretion of oestradiol-17β from the grafted ovary is not involved in the occurrence of the FSH surge. These results indicate that a selective release of FSH can be induced in castrated male rats bearing an ovarian transplant probably due to decreased secretion of inhibin by the luteinized follicles in the grafted ovaries. Sex differentiation of the hypothalamus is not, therefore, involved in the selective surge of FSH. J. Endocr. (1985) 106, 31–36


1960 ◽  
Vol XXXIV (II) ◽  
pp. 176-188 ◽  
Author(s):  
A. Hasselblatt ◽  
Ch. Ratabongs

ABSTRACT The effect of pregnant mare serum gonadotrophin (PMS) and human chorionic gonadotrophin (HCG) on the thyroid gland of normal, of gonadectomized and of hypophysectomized infantile rats has been studied. Gonadotrophin treatment stimulated the thyroid of normal and hypophysectomized female rats. A corresponding effect was not observed in gonadectomized female or in normal and gonadectomized male rats. These results show that the gonadotrophic hormones stimulate thyroid function indirectly by increasing the hormonal secretion of the ovaries. An intimate functional relationship between the ovaries and the thyroid gland was thus demonstrated. As the stimulating effect of gonadotrophin treatment was also present in hypophysectomized female rats, it was concluded that the oestrogens act directly on the thyroid gland. Their thyrotrophic action is not mediated by the pituitary gland.


1981 ◽  
Vol 89 (3) ◽  
pp. 379-387 ◽  
Author(s):  
D. J. SAPHIER ◽  
R. G. DYER

Action potentials were recorded from 174 neurones in the mediobasal hypothalamus of ovariectomized adult female rats exposed neonatally to monosodium glutamate (MSG) and from 145 neurones in control rats. All of the animals, which were anaesthetized with urethane, had been ovariectomized for at least 3 weeks and received two injections of oestradiol benzoate (20 μg/100 g body weight, i.m.) 72 h and immediately before the recording experiments. The response of each neurone to electrical stimulation of the median eminence and rostral hypothalamus (preoptic and anterior hypothalamic areas; PO/AH) was analysed. The most striking feature of the results obtained was the significant (P < 0·001) loss of inhibitory responses in those neurones remaining in the adult rats after neonatal treatment with MSG. The loss of inhibitory responses applied to both stimulation sites. In each rat the response of one neurone, which was antidromically identified as projecting to the median eminence, was recorded before and during stimulation of the PO/AH at 50 Hz for 30 s in every min for 15 min. Before and after this stimulation blood was collected from a jugular vein for estimation by radioimmunoassay of concentrations of prolactin and TSH. In the MSG-treated rats significantly (P < 0·05) fewer neurones were inhibited by the 50 Hz stimulation than in control rats. In control rats the plasma concentrations of prolactin nearly quadrupled as an immediate consequence of this treatment, whereas in MSG-treated rats plasma concentrations barely doubled. However, in the MSG-treated rats plasma concentrations of prolactin continued to rise after stimulation ceased, possibly as a consequence of enhanced secretion of thyrotrophin releasing hormone.


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