Transcription hormonal regulation

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

The signal is what starts everything off. Signals take a variety of forms, but for our purposes there are only two. The first type are signals that go into the cell, bind to internal receptors, and exert their effects. Steroid hormones, vitamin D, thyroid hormone, and retinoids are the only members of this class. All of the intracellular receptors ultimately activate the transcription of regulated genes. The common feature of signals that enter the cell is that they are all small lipophilic molecules that can cross the cell membrane. 

Steroid hormones Stimulates transcription of hormone-regulated genes... 

Kulkarni, A. B., Gubits, R. M. and Feigelson, P. (1985) Developmental and hormonal regulation of alpha 2u-globulin gene transcription. Proc. Natl. Acad. Sci. U S A 82, 2579-82. 

The HREs are components of the control region of hormone-regulated promotors. Typically, the binding of the activated, hormone-bound receptor to the HRE stimulates the expression of the cognate genes. The mechanisms of transcription activation still remains speculative. Many proteins have been identified which act as coactivators, i.e. they interact with the activated receptor (review Glass et al., 1997). The nature of these proteins suggest that at least two, separate but not mutually exclusive pathways of transcription activation must be considered ... 

Zhang J., Saleh D. S. and Wyatt G. R. (1996) Juvenile hormone regulation of an insect gene a specific transcription factor and a DNA response element. Mol. Cel. Endocrin. 122, 15-20. 

Fig. 1. A model for the mechanism whereby steroid hormones regulate rates of gene transcription. Steroids (S) bind with receptors (R) to form a steroid-receptor complex that interacts with DNA sequences called hormone response elements (HRE). These HREs are at variable distances from the gene promoter which frequently consists of upstream promoter elements (UPE) and conserved elements such as TATA box (TATA).

Figure 29-6. Gene transcription is regulated by retinoic acid.Ah-Zrwm-retinoic acid and 9-cA-retinoic acid are ligands for retinoic acid receptors (RARs) and retinoid X receptors (RXRs), respectively. The RXRs can form heterodimers with RARs and with the thyroid hormone receptors (TRs), the vitamin D receptor (VDR), and the peroxisome proliferator-activated receptors (PPARs) and a number of other hormone- and nutrient-responsive transcription factors to moderate gene transcription. Because of the ability of RXR to form heterodimers with other nuclear receptors, vitamin A has abroad effect on many hormonally and nutrient-responsive genes.

Simons SS Jr, Oshima H, Sz ary D. Higher levels of control modulation of steroid hormone-regulated gene transcription. Mol. Endocrinol. 1992 6 995-1002. 

H.S. Sul and D. Wang, Nutritional and hormonal regulation of enzymes in fat synthesis Studies on fatty acid synthase and mitochondrial glycerol-3-phosphate acyltransferase gene transcription, Annu. Rev. Nutr., 1998, 18, 331-351. 

Le Goff, P., Montano, M.M., Schodin, D.J. and Katzenellenbogen, B.S. (1994) Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity. The Journal of Biological Chemistry, 269, 4458-4466. 

Finally, examples of physiologieal and nutritional stimuli impacting on these transcriptional sensors will be provided. This will lead us to focus on SREBPl-c and PPARa within complex regulatory networks of dietary and hormonal regulations in the liver. 

Hormonal regulation of A desaturase is complex and not fully understood. Rats with genetic diabetes, or made diabetic by destruction of pancreatic p-cells, have depressed A desaturase activity in liver, mammary gland and adipose tissue which is restored in vivo by insulin. Insulin appears essential for basal transcription of the SCDl gene and, as described before, SREPB appears to be the key regulator (Rimoldi et al., 2001 Waters and Ntambi,... 

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