Early Events in the Steroidal Regulation of α_2u Globulin in Rat Liver

Abstract

1. A double-antibody radioimmunoassay for azU globulin has been developed. With the help of this highly sensitive radioimmunoassay the early effects of both androgen and estrogen treatments on the hepatic synthesis of azU globulin in the rat have been investigated.2. Results show that the earlier observation of the long lag period in the androgenic induction of azU globulin is more apparent than real.3. Single injections of either Sa-dihydrotestosterone (Sa-dihydro-17~-hydroxy-4-androsten-3-one) or its physiological antagonist estradiol-17P (1,3,5(1O)-estratriene-3,17fl-diol) to castrated female rats resulted in the induction of azU globulin reaching maximum hepatic level of the protein between 6 -9 h after the hormone administration. Administration of cycloheximide 15 min prior to hormone treatment blocked both androgenic and estrogenic induction of mu globulin.4. Daily pretreatments with 5a-dihydrotestosterone increased the sensitivity of subsequent androgenic response to azU globulin synthesis. On the other hand, daily pretreatments with estradiol17p decreased and ultimately abolished the estrogenic induction of azu globulin.5. The possible mechanism of both androgenic and estrogenic induction of azU globulin in rat liver mediated through a sex-hormone-binding protein with dual affinity for both dihydrotestosterone and estradiol has been suggested. a2,, Globulin is the principal urinary protein in the mature male rat and the hepatic origin of the protein has been well documented [1-31. m u globulin is absent in the female and immature male rat; it appears initially in the male at the time of puberty (6-7 weeks of age) and reaches peak levels at about 12 weeks of age [4-61. Androgen treatment of spayed female rats has been found to result, after an initial lag period of 3-4 days, in the induction of both azu globulin and its corresponding messenger RNA (mRNA) in the liver [4,7]. On the other hand, estrogen treatment to mature male rats results in the suppression and ultimately complete inhibition of azU synthesis [4]. A cytosol androgen-binding protein in rat liver with additional affinity for estradiol17p has been identified [8]. There appears to be a strong correlation between the presence of this androgen-binding protein and the androgen-dependent synthesis of azu globulin in rat liver. Prepubescent, senescent and pseudohermaphrodite male rats which do not contain this hepatic androgen-binding protein This paper is dedicated to the memory of Professor Arthur H. Smith.Trivial Names. Estradiol-17p or estradiol, 1,3,5(10)-estratriene-3,17/?-diol; 5a-dihydrotestosterone or dihydrotestosterone, 5a-dihydro-17P-hydroxy-4-androsten-3-one. also do not respond to androgen treatment with azU induction. Androgen treatment to castrated female rats results in the rise of the level of the cytosol androgen-binding protein and on the other hand, estrogen treatment leads to gradual decrease and ultimate loss of the androgen-binding protein of rat liver [8,91. The body of experimental evidence on steroidal regulation of gen...

Purification and immunochemical characterization of the cytoplasmic androgen-binding protein of rat liver

“…Western blot data show that the antibody reacts with only a 31-kDa band, which indicates the monospecificity of the antiserum. A gradual decline and ultimate loss of the CAB activity during aging, as determined previously both by sucrose density gradient analyses and by photoaffinity labeling (Roy et al, 1974;Roy 1977), have now been confirmed by the age-dependent loss of the immunoreactive 31-kDa androgenbinding protein. Androgen treatment of prepubertal, senescent, and testicular feminized male rats fails to induce c^u'globulin.…”

“…In addition, sucrose gradient analysis failed to show any CAB activity in these animals after androgen treatment (Roy et al, 1983a). Androgen treatment of ovariectomized females, on the other hand, first results in the appearance of the CAB protein and, subsequently, androgen sensitivity with the concomitant induction of a2u-globulin (Roy et al-> 1974;Roy, 1977).…”

Reversible alteration of hepatic messenger RNA species for peroxisomal and non-peroxisomal proteins induced by the hypolipidaemic drug Wy-14,643

“…Table 1. Effect of Wy-14,643 on the hepatic concentration of a2b-globulin in the male rat Hepatic cytosol preparations from animals with different treatments were assayed for a2.-globulin by radioimmunoassay (Roy, 1977) and total protein (Lowry et al, 1951). The results are means of the individual values shown in parentheses.…”

“…Determination of the cytoplasmic content of a2uglobulin Preparation of rat liver cytosol and its radioimmunoassay for a2u-globulin have been described (Roy, 1977;Chatterjee et al, 1983).…”

Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice.

“…This sex difference in AR expression also correlates with the androgen responsiveness of the liver in young adult male and female rats (17). Furthermore, irrespective of sex, expression of the AR in the liver is regulated in an age-dependent manner; i.e., it is almost undetectable before puberty, rises rapidly in postpubertal life, and gradually declines during aging, reaching an almost nondetectable level after about 22-24 months of age (18).…”