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Title:Estrogen and Antiestrogen Action in the Medial Basal Hypothalamus and Pituitary: Dopamine-Prolactin Interrelationships (d-2 Receptors, Bromocriptine)
Author(s):Toney, Thomas Wesley
Department / Program:Physiology and Biophysics
Discipline:Physiology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Biology, Animal Physiology
Abstract:The actions of estradiol and antiestrogens on dopamine turnover and prolactin levels were studied in the medial basal hypothalamus (MBH), anterior pituitary, and serum of immature female rats. Estradiol increased MBH dopamine levels and turnover and pituitary and serum prolactin concentrations in a time- and concentration-dependent manner. The antiestrogens LY 117018, monohydroxytamoxifen (TAM-OH), CI 628, and tamoxifen competed with estradiol for binding to the MBH estrogen receptor and displayed relative binding affinities of 190%, 185%, 6.7%, and 1.4% with estradiol set at 100%, similar affinities to those found for uterine estrogen receptors. The antiestrogens increased dopamine turnover rates only two-fold and they antagonized the estrogen-induced five-fold increase in dopamine turnover rates very successfully. In animals treated with bromocriptine, estradiol and antiestrogens failed to increase the low serum prolactin levels, yet they evoked significant ca. two-fold increases in dopamine turnover rates and nearly two-fold increases in MBH dopamine content. Hence, a part of the actions of estradiol and the antiestrogens on MBH dopamine appears to be exerted independently of changes in circulating prolactin, and may occur by direct action of these compounds on the estrogen receptor system present in the MBH. The four antiestrogens as well as t-butylphenoxyethyl diethylamine (BPEA), a compound that does not bind to the estrogen receptor but does interact with the antiestrogen binding site (AEBS), were found to compete with spiroperidol for binding to the D-2 dopamine receptor in corpus striatum and pituitary membranes and displayed relative binding affinities ranging from 0.4-0.06% with spiroperidol set at 100%. Even though the antiestrogens can interact with D-2 receptor sites on the pituitary, it is more likely that their effects on prolactin synthesis and release are mediated by their interactions with estrogen receptor due to their high degree of lipophillicity and non-specific binding which would interfere with D-2 receptor interaction.
Issue Date:1986
Type:Text
Description:105 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1986.
URI:http://hdl.handle.net/2142/71447
Other Identifier(s):(UMI)AAI8701636
Date Available in IDEALS:2014-12-16
Date Deposited:1986


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