Structure-activity relationships of sex steroid analogs determined in vitro in a thyroid hormone-responsive membrane Ca2+-ATPase model.

Abstract:

:Physiological concentrations of L-T4 were found previously to stimulate Ca2+-ATPase activity in vitro in reticulocyte membranes from female rabbits and to inhibit this enzyme in reticulocyte membranes from males. In these previous studies, preincubation of intact cells or ghosts with testosterone (5 X 10(-11) M) converted female-source reticulocyte membranes to male-type responsiveness to thyroid hormone (inhibition of Ca2+-ATPase activity). Preincubation of reticulocyte membranes with 17 beta-estradiol (5 X 10(-11) M) converted male-source membranes to female-type responsiveness (stimulation by L-T4 of membrane Ca2+-ATPase activity). Using this sex steroid-sensitive thyroid hormone-dependent membrane enzyme system, we investigated the structure-activity relationships of analogs of sex steroids and unrelated steroids. 5 beta-Androstanes were active compared to testosterone in assays using female-source membranes, while 5 alpha-androstanes were less active. Within the 5 beta-androstanes, activity was dependent on at least one hydroxyl group at the C3- or C17-position. Nongonadal steroids tested were less active, establishing specificity of the sex steroid effect in assays using female-source membranes. Assayed in male-source membranes, estrone and 3-hydroxy-1,3,5-(10)7-estratraen-17-one (equilin) were active compared for estrogen effect with 17 beta-estradiol, while estriol was less active. The activities of hydrocortisone and aldosterone were 76% and 71%, respectively, in this system. These structure-activity relationships are distinct from those described for gonadal steroid-cytoplasmic binding proteins or nuclear interactions, and represent a novel sex steroid-thyroid hormone effect on activity of a membrane enzyme.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Lawrence WD,Osawa YM,Davis PJ,Blas SD

doi

10.1210/endo-119-6-2803

subject

Has Abstract

pub_date

1986-12-01 00:00:00

pages

2803-8

issue

6

eissn

0013-7227

issn

1945-7170

journal_volume

119

pub_type

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