Complementary DNA clones encoding the human vitamin D receptor have been isolated from human intestine and T47D cell cDNA libraries. The nucleotide sequence of the 4605-base pair (bp) cDNA includes a noncoding leader sequence of 115 bp, a 1281-bp open reading frame, and 3209 bp of 3' noncoding sequence. Two polyadenylylation signals, AATAAA, are present 25 and 70 bp upstream of the poly(A) tail, respectively. RNA blot hybridization indicates a single mRNA species of approximately equal to 4600 bp. Transfection of the cloned sequences into COS-1 cells results in the production of a single receptor species indistinguishable from the native receptor. Sequence comparisons demonstrate that the vitamin D receptor belongs to the steroid-receptor gene family and is closest in size and sequence to another member of this family, the thyroid hormone receptor.

https://www.pnas.org/content/pnas/85/10/3294.full.pdf

Cloning and expression of full-length cDNA encoding human vitamin D receptor.

Material dealing with the chemistry, biochemistry, and biological activities of oxysterols is reviewed for the period 1987-1995. Particular attention is paid to the presence of oxysterols in tissues and foods and to their physiological relevance.

Review of progress in sterol oxidations: 1987–1995

Although it has been recognized for many years that oestrogen is a key component in the maintenance of normal bone balance, the mechanisms by which oestrogen exerts its influence have remained unresolved. Recent identification of oestrogen receptors in both bone-forming osteoblasts and bone-resorbing osteoclasts has opened up exciting new areas of research on the direct effects of oestrogen on both osteoblasts and osteoclasts. This review presents an updated model for the molecular mechanisms involved in oestrogen action, the mechanism of anti-oestrogen action, and outlines recent advances in knowledge of oestrogen effects on osteoblasts, osteoclasts, and the coupling of bone resorption and bone formation.

Oestrogen Effects on Osteoblasts and Osteoclasts

The level of an MRNA in the cytoplasm represents a balance between the rate at which the mRNA precursor is synthesized in the nucleus and the rates of nuclear RNA processing and export and cytoplasmic mRNA degradation. Although most studies of gene expression have focused on gene transcription and its control, a great deal of information indicates that mRNA degradation and its regulation are major control mechanisms that help govern cellular mRNA levels. The objective of this chapter is not to exhaustively review our present knowledge in the area of eukaryotic mRNA degradation, but to provide a short general discussion of the importance of mRNA degradation and its regulation and a brief overview of recent findings and present knowledge. The overview is followed by a more in-depth discussion of one of the several pathways for mRNA degradation. We concentrate on the pathway for regulated mRNA degradation mediated by mRNA-binding proteins and endonucleases that cleave within the body of mRNAs. As a potential example of this type of control, we focus on the regulated degradation of the egg yolk precursor protein vitellogenin on the mRNA-binding protein vigilin and the mRNA endonuclease polysomal ribonuclease 1 (PMR-1).

Regulation of pathways of mRNA destabilization and stabilization.

Hormone-dependent phosphorylation of the avian progesterone receptor

1. Immunocharacterization of the nuclear acceptor sites for the avian oviduct progesterone receptor.- 2. Immunological analysis of the avian progesterone receptor.- 3. Purification, structure and function of the chick oviduct progesterone receptor: remaining questions in 1986.- 4. Novel mechanisms for regulation of mammalian estrogen and progesterone receptors.- 5. Hormones and oncogenes in human breast cancer.- 6. Estrogen control of vitellogenin gene transcription and mRNA stability.- 7. Nuclear acceptor sites for the mammalian estrogen receptor: effects of antiestrogens.- 8. Phosphorylation reactions associated with the glucocorticoid receptor.- 9. Structure and function of cytosolic glucocorticoid receptors in WEHI-7 mouse thymoma cells: receptor composition and phosphorylation.- 10. Inhibition of glucocorticoid receptor conversion to the DNA-binding state and inhibition of subunit dissociation.- 11. Glucocorticoid regulation of proto-oncogene expression and cellular proliferation.- 12. Steroid regulation of rRNA synthesis.- 13. Variations in agonist activity among antiglucocorticoid steroids and its relation to glucocorticoid regulated genes.- 14. On the mechanism of action of aldosterone.- 15. Regulation of epithelial Na+ transport by aldosterone.- 16. Messenger RNA-S14 as a model of thyroid hormone action at the hepatocellular level.- 17. The 1,25-Dihydroxycholecalciferol receptor.- 18. Receptors for 1,25-dihydroxyvitamin D3: Structural comparisons and recent functional insights.- 19. Vitamin D-dependent calcium-binding protein gene: cDNA cloning, mRNA distribution and regulation in the rat.- 20. The physiology and biochemistry of vitamin D-dependent calcium binding proteins.- 21. The oxysterol receptor.

T. C. Spelsberg

Papers

Steroid and Sterol Hormone Action