scholarly journals Rapid Action of Estrogens on Intracellular Calcium Oscillations in Primate Luteinizing Hormone-Releasing Hormone-1 Neurons

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 1155-1162 ◽  
Author(s):  
Hideki Abe ◽  
Kim L. Keen ◽  
Ei Terasawa

Feedback controls of estrogen in LHRH-1 neurons play a pivotal role in reproductive function. However, the mechanism of estrogen action in LHRH-1 neurons is still unclear. In the present study, the effect of estrogens on intracellular calcium ([Ca2+]i) oscillations in primate LHRH-1 neurons was examined. Application of 17β-estradiol (E2, 1 nm) for 10 min increased the frequency of [Ca2+]i oscillations within a few minutes. E2 also increased the frequency of [Ca2+]i synchronization among LHRH-1 neurons. Similar E2 effects on the frequency of [Ca2+]i oscillations were observed under the presence of tetrodotoxin, indicating that estrogen appears to cause direct action on LHRH-1 neurons. Moreover, application of a nuclear membrane-impermeable estrogen dendrimer conjugate, not control dendrimer, resulted in a robust increase in the frequencies of [Ca2+]i oscillations and synchronizations, indicating that effects estrogens on [Ca2+]i oscillations and their synchronizations do not require their entry into the cell nucleus. Exposure of cells to E2 in the presence of the estrogen receptor antagonist ICI 182,780 did not change the E2-induced increase in the frequency of [Ca2+]i oscillations or the E2-induced increase in the synchronization frequency. Collectively, estrogens induce rapid, direct stimulatory actions through receptors located in the cell membrane/cytoplasm of primate LHRH-1 neurons, and this action of estrogens is mediated by an ICI 182,780-insensitive mechanism yet to be identified.

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.


2005 ◽  
Vol 89 (6) ◽  
pp. 3741-3756 ◽  
Author(s):  
J.M.A.M. Kusters ◽  
M.M. Dernison ◽  
W.P.M. van Meerwijk ◽  
D.L. Ypey ◽  
A.P.R. Theuvenet ◽  
...  

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