Estradiol β Receptor Expression on Human B-lymphocytes in Response to
Effects of 17-β-estradiol on the ontogenesis of striatal dopaminergic receptors
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Pharmacological Research, Vol. 22, Supplement 3.1990 EFFECTS OF 17-B-ESTRADIOL ON THE ONTOGENESIS OF STRIATAL DOPAMINERGIC RECEPTORS Marinella Blengio, Carlo Ferretti, Alfredo Garzino Demo, Piera Ghi* and Enrico Genazzani Istituto di Farmacologia e Terapia Sperimentale, via P. Giuria 13, Torino e *Istituto di Farmacologia e Farmacognosia, corso Raffaello 31, Torino. Estradiol (E 2) modulates the activity of the striatal dopaminergic (DA) system in the rats. Its administration to rats of both sexes induces behaviour and biochemical changes indicative of diminished or increased DA functions. It has been shown that low doses given for short periods produce DA neuron system alteration similar to those induced by DA agonists, whereas high doses given for more than three days produce alterations similar to those induced by its agonists (I, 2). It can thus be supposed that several mechanisms are involved in the modification of DA transmission by E 2. Its agonistic action (rapid onset, low dose) is thought to be responsible for modification at the synaptic level, whereas the antagonistic action is probably due to enhanced genic synthesis of new receptors and not dependent on the interaction of DA receptors. Since these receptors are known to increase from birth to a plateau around the 40th day of life (3), the possibility that E 2 might alter their maturation in this period in a dose and time dependent manner (as in the adult) was investigated. Doses of 10 for 3 days and 50 for 6 days were therefore administered to male and female rats aged IS, 21 and 40 days. It was found that E 2 produced two different effects probably attributabled to distinct mechanisms involved in the regulation of DA transmission. The low dose caused a diminution, irrespective of age and sex, whereas the high dose was correlated with both parameters: in 15 days old rats, receptors increased in both sexes, whereas this action disappeared with age in females only. It may thus be concluded that the response of DA receptors to low dose of E 2 was already present in very early life, suggesting a full functional efficiency. 23 I043-66 I8/90/22III0023--D2/$03 .00/0 © 1990 The Italian Pharmacological Society
Transcript of Effects of 17-β-estradiol on the ontogenesis of striatal dopaminergic receptors
Pharmacological Research, Vol. 22, Supplement 3.1990
EFFECTS OF 17-B-ESTRADIOL ON THE ONTOGENESIS OF STRIATALDOPAMINERGIC RECEPTORS
Marinella Blengio, Carlo Ferretti, Alfredo Garzino Demo,Piera Ghi* and Enrico Genazzani
Istituto di Farmacologia e Terapia Sperimentale, via P. Giuria 13, Torino e*Istituto di Farmacologia e Farmacognosia, corso Raffaello 31, Torino.
Estradiol (E2) modulates the activity of the striatal dopaminergic (DA)
system in the rats. Its administration to rats of both sexes induces
behaviour and biochemical changes indicative of diminished or increased DA
functions. It has been shown that low doses given for short periods produce
DA neuron system alteration similar to those induced by DA agonists, whereas
high doses given for more than three days produce alterations similar to
those induced by its agonists (I, 2). It can thus be supposed that several
mechanisms are involved in the modification of DA transmission by E2. Its
agonistic action (rapid onset, low dose) is thought to be responsible for
modification at the synaptic level, whereas the antagonistic action is
probably due to enhanced genic synthesis of new receptors and not dependent
on the interaction of DA receptors. Since these receptors are known to
increase from birth to a plateau around the 40th day of life (3), the
possibility that E2 might alter their maturation in this period in a dose
and time dependent manner (as in the adult) was investigated. Doses of 10
~g/kg for 3 days and 50 ~g/kg for 6 days were therefore administered to male
and female rats aged IS, 21 and 40 days. It was found that E2 produced two
different effects probably attributabled to distinct mechanisms involved in
the regulation of DA transmission. The low dose caused a diminution,
irrespective of age and sex, whereas the high dose was correlated with both
parameters: in 15 days old rats, receptors increased in both sexes, whereas
this action disappeared with age in females only. It may thus be concluded
that the response of DA receptors to low dose of E2 was already present in
very early life, suggesting a full functional efficiency.
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I043-66 I8/90/22III0023--D2/$03 .00/0 © 1990 The Italian Pharmacological Society
24 Pharmacological Research. Vol. 22. Supplement 3. 1990
Tab. Effects of E2 treatment on striatal DA receptors, in male and femalerats of different age.
Bmaxfmol/mg/prot.
15 days
H F
21 days
M F
40 days
M F
Controls 173:1:14 215:1:33 220:1:10 236:t36 254:t16 282:t12n=4 n=3 n=3 n=3 n"'6 n=5
Estradiol 139:t14* 148:1:7* 178:t30* 150:1:10* 195:t17* 239:1:10*10 p.g/kg n=3 n"'3 n=3 n=3 n=3 n=3
Estradiol 263:1:10* 284:1:13* 297:1:44* 260:1:40 338:1:54* 275:1:2450 p.g/kg n=3 n..3 n=3 n"'3 n=3 n=4---------------------------------------------------------------------------*p< 0.05 vs. same age controls by Kruskall-Wallis and Hann-Whitney tests.Animals were treated with E2 killed by decapitation 24 h after the lastinjection and 3H-Spiperone binding was performed according to Creese et al(4). The Kd values were unchanged in all groups and were ranged to 0.40-0.50 nM.
Since the effects of high dose of E2 was more evident in the initial growth
stage and was also sex related, it seems probable that the maturation of new
receptors at the genetic level is involved, since this would explain the
subsequently depressed response in female only. The sensibility to .l ow dose
of E2 may represent a fisiological response to the changes in hormone levels
that occur during estrus cycle. The refractoriness to high dose of E2 may
serve a functional purpose by preserving dopamine receptors from the high
hormone levels that occur during pregnancy.
References
1. Van Hartesveldt C. and Joyce J.N . Effects of estrogen on the basalganglia. Neurosc. Biobehav. Rev. 1986; 10: 1-14
2. Ferretti C., Ghi P., Blengio H., Gaietta G., Barrera G. and Genazzani E.Are the catecholestrogens involved in estrogen induced striatal dopaminereceptor supersesitivity. Eur J. Pharmacol. 1989; 166 :149-156.
3. Gelbard H.A., Teicher H.A., Faedda G. and Baldessarini R.J.: Postnataldevelopment of dopamine D1 and D2 receptor site in rat striatum. Brain Res.1989; 49:123-130.
4. Creese 1., Steward K., and Snyder S.H. Species variations in dopaminereceptor binding. Eur J. Pharmac . 1979; 60: 55-66.
