Catecholamine synthesis inhibitors acutely modulate [3H]estradiol binding by specific brain areas and pituitary in ovariectomized rats.
Drugs known to alter endogenous levels of catecholamines were administered to adult ovariectomized rats to assess catecholaminergic effects on estradiol (E2) uptake and binding in nuclear and supernatant fractions of pituitary and specific brain regions and on cytoplasmic E2 receptor numbers and affinities. Specific (i.e. diethylstilbestrol-blockable) binding in vivo was measured 1 h after the iv injection of [3H]E2 (1 micrograms/kg). Administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (alpha MPT) 2 h before [3H]E2, to reduce levels of dopamine (DA), norepinephrine (NE), and epinephrine (Ep), decreased total and specific [3H]E2 binding by 36-56% in the nuclear fraction of the anterior pituitary, basal hypothalamus, and anterior hypothalamus. The dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate (DDC), administered 2 h before [3H]E2 to reduce levels of only NE and Ep, increased the total and specific uptake of [3H]E2 by 62-140% in nuclear and supernatant fractions of the anterior pituitary and also increased uptake in several brain areas. In vitro analysis of hypothalamic and pituitary cytoplasms showed that in vivo administration of DDC increased E2 binding. Scatchard analysis showed that DDC increased receptor numbers 18-29%, with no change in the dissociation constant in pituitary cytoplasms. At the same time, plasma PRL levels were reduced by DDC treatment, indicating that DDC had increased DA output. Phenoxybenzamine (a blocking agent at alpha 1 postsynaptic binding sites) and a high dose of clonidine (a pre- and postsynaptic alpha-receptor agonist) did not significantly alter specific uptake in the cell nuclear fraction of any tissue, suggesting that postsynaptic alpha-receptors do not play a major role in modulating [3H]E2 uptake. No drug altered plasma levels of radioactivity. Because alpha-methyl-p-tyrosine and DDC both inhibit synthesis of NE and Ep, it is suggested that their opposite effects on uptake of [3H]E2 are related to their opposite effects on DA output. This interpretation is compatible with our previous observations that DA agonists increase [3H]E2 uptake in brain and pituitary in ovariectomized rats.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002369:Castration; D002395:Catecholamines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D003000:Clonidine / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D008781:Methyltyrosines / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010902:Pituitary Gland / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D010643:Phenoxybenzamine; D004958:Estradiol; D019805:alpha-Methyltyrosine; D011388:Prolactin; D004050:Ditiocarb; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D003000:Clonidine