This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by THOMPSONS, M. A. Articles by CONWAY, S. Search for Related Content PubMed PubMed Citation Articles by THOMPSONS, M. A. Articles by CONWAY, S.

Catecholamine Synthesis Inhibitors Acutely Modulate [³H]Estradiol Binding by Specific Brain Areas and Pituitary in Ovariectomized Rats^*

MARGARET A. THOMPSONS, DOROTHY E. WOOLLEY, DOROTHY W. GIETZEN and SONYA CONWAY

Department of Animal Physiology, University of California Davis, California 95616

Abstract

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 µg/ kg). Administration of the tyrosine hydroxylase inhibitor amethyl- p-tyrosine (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-(β-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 ₁ postsynaptic binding sites) and a high dose of clonidine (a pre- and postsynaptic -receptor agonist) did not significantly alter specific uptake in the cell nuclear fraction of any tissue, suggesting that postsynaptic -receptors do not play a major role in modulating [³H]E₂ uptake. No drug altered plasma levels of radioactivity. Because -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. (Endocrinology 113: 855, 1983)

Footnotes

^* This work was supported by NIH Grant HD-12385.

Present address: Zoological Society of San Diego, P.O. Box 551,San Diego, California 92112.

To whom all correspondence and requests for reprints should be addressed.

Present address: Department of Physiology, University of Texas Southwestern Medical School at Dallas, Dallas, Texas 75235.

Received August 2, 1982.

This article has been cited by other articles:

				C. N. Epperson, K. L. Wisner, and B. Yamamoto Gonadal Steroids in the Treatment of Mood Disorders Psychosom Med, September 1, 1999; 61(5): 676 - 697. [Abstract] [Full Text] [PDF]