Influence of neonatal androgenization on the expression of α2u-globulin in rat liver and submaxillary gland

doi:10.1016/0022-4731(85)90004-4

Journal of Steroid Biochemistry

Volume 23, Issue 5, Part 1, November 1985, Pages 557-565

https://doi.org/10.1016/0022-4731(85)90004-4 Get rights and content

Abstract

We studied the influence of neonatal androgenization on the serum level of α_2u-globulin, the level of the corresponding mRNA in liver and submaxillary gland and the concentration of an androgen and oestrogen binding protein in liver cytosol. Male rats gonadectomized on day 15 (after the neonatal surge of androgen secretion) were used as neonatally androgenized animals, their female littermates gonadectomized at the same age served as controls. Using a sensitive radioimmunoassay it could be demonstrated that only very low levels of α_2u-globulin are present in adult female control animals. Neonatal androgenization increases these levels some 14-fold. Stimulation with testosterone or dexamethasone results in a relative increase in the serum levels in animals of both sexes. After 11 days of treatment with testosterone propionate or dexamethasone, however, the final α_2u-globulin levels are respectively 1.8 times and 8 times higher in neonatally androgenized rats as compared to their female littermates. The concentration of the androgen and oestrogen binding protein in rat liver cytosol displays parallel sex differences in unstimulated animals and parallel changes after treatment with androgens and glucocorticoids. Measurements of α_2u-globulin mRNA by dot blot hybridization and by translation in reticulocyte lysate show a good correlation between the serum levels of α_2u-globulin and the corresponding mRNA in the liver. The abundance of α_2u-globulin mRNA in submaxillary gland is not influenced by neonatal androgens or hormone treatment during adulthood. These data suggest that neonatal androgenization directly or indirectly influences the availability for transcription and/or the transcription rate of α_2u-globulin genes in the liver.

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Androgens are the main hormones responsible for the induction of the male phenotype. This process involves a complex combination of reversible and irreversible effects. As for other steroid hormones, many of the effects of androgens are mediated by a specific intracellular receptor that interacts with cis-acting regulatory regions (AREs) in the affected genes. Apart from these direct effects, however, androgens may indirectly affect the expression of a variety of genes that do not necessarily contain AREs. Indirect effects may be related to androgen-induced changes in the concentration or activity of secondary transcription factors, autocrine and paracrine mediators, and circulating hormones. Such indirect effects may induce cascade-like actions and may play an important role in more complex effects of androgens involving coordinated responses of genes, cells and organs.
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The binding of androgen-receptor complexes to fragments derived from two α_2u-globulin genes (RAP 01 and RAO 01) was studied using a DNA-cellulose competition assay. Rat prostate cytosol labelled with [³H]mibolerone was used as a source of the androgen receptor. Two controls were included in these studies: the long terminal repeat (LTR) of mouse mammary tumor virus which has previously been shown to act as an androgen response element and a fragment of the C3 gene of prostatic binding protein which has been demonstrated to bind androgen-receptor complexes. Our experiments indicate that androgen-receptor complexes bind specifically and with comparable affinity to the C3 gene fragment, the LTR and a fragment of RAP 01 located in the 5'-upstream region (bp −642 up to −584). No specific interaction was observed with fragments derived from RAO 01. The region of RAP 01 which binds androgen-receptor complexes has previously been shown to interact with glucocorticoid receptors and contains a 17 bp sequence homologous with the consensus sequence for glucocorticoid-receptor binding. A mutation in this sequence in RAO 01 may be responsible for the loss of glucocorticoid and androgen-receptor binding. It is concluded that at least one member of the α_2u-globulin gene family interacts directly with androgen-receptor complexes with an affinity comparable to that observed for other androgen-dependent genes. The binding is observed in a region displaying also affinity for the glucocorticoid receptor.
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Influence of neonatal androgenization on the expression of α2u-globulin in rat liver and submaxillary gland

Abstract

Recent Prog. Horm. Res.

FEBS Lett.

J. biol. Chem.

Cell

Cell

Biochim. biophys. Acta

FEES Lett.

J. biol. Chem.

J. molec. Biol.

FEBS Lett.

Recent Prog. Horm. Res.

Differentiation

J. steroid Biochem.

Cell

Identification of rat urinary protein by zone and immunoelectrophoresis

Androgen-dependent synthesis of α2u-globulin in the rat: role of the pituitary gland

J. Endocr.

Effect of thyroid hormone on the level of he hepatic mRNA for α2u-globulin

Biochemistry

Hormonal modulation of specific messenger RNA species in normal and neoplastic rat liver

Adv. Enzym.

Glucocorticoid induction of hepatic α2u-globulin synthesis and messenger RNA level in castrated male rats in vivo

J. biol. Chem.

Influence of neonatal androgenization on the expression of α_2u-globulin in rat liver and submaxillary gland

Androgen-dependent synthesis of α_2u-globulin in the rat: role of the pituitary gland

Effect of thyroid hormone on the level of he hepatic mRNA for α_2u-globulin

Glucocorticoid induction of hepatic α_2u-globulin synthesis and messenger RNA level in castrated male rats in vivo