Hormone responsiveness

As we have seen in this chapter steroids have a number of functions in human physiology Cholesterol is a component part of cell mem branes and is found in large amounts in the brain Derivatives of cholic acid assist the digestion of fats in the small intestine Cortisone and its derivatives are involved in maintaining the electrolyte balance in body fluids The sex hormones responsible for mascu line and feminine characteristics as well as numerous aspects of pregnancy from conception to birth are steroids... 

Transport in the blood is no longer a requisite for a hormonal response. Responses can occur after release of hormones into the interstitial fluid with binding to receptors in nearby ceUs, called paracrine control, or binding to receptors on the ceU that released the hormone, called autocrine control. A class of hormones shown to be synthesized by the tissue in which they act or to act in the local ceUular environment are the prostaglandins (qv). These ubiquitous compounds are derived from arachidonic acid [506-32-1] which is stored in the ceU membranes as part of phosphoHpids. Prostaglandins bind to specific ceUular receptors and act as important modulators of ceU activity in many tissues. 

The primary hormone responsible for conversion of glucose to glycogen is insulin (Figure 6.36). Insulin is secreted by special cells in the pancreas called the islets of Langerhans. Secretion of insulin is a response to increased glucose in the... 

Insulin is a hormone responsible for the regulation of glucose levels in the blood. An aqueous solution of insulin has an osmotic pressure of 2.5 mm Hg at 25°C. It is prepared by dissolving 0.100 g of insulin in enough water to make 125 mL of solution. What is the molar mass of insulin ... 

A gene activity profile is a collection of quantitatively determined levels of gene products, found in one tissue or cell type, which is characteristic of the tissue, a disease process, a hormone response, a pharmaceutical intervention, etc. 

In breast cancer patients, total PR status is measured for hormonal treatment. The presence of PR is associated with increased survival rates and hormonal responsiveness of mammary tumors. PR agonists are widely used in contraception, HRT, breast cancer, and endometrial hyperplasia. Antiprogestins such as RU486 are used for blocking ovulation and preventing implantation, and in addition they are in clinical testing for the induction of labor and to control various neoplastic transformations. 

Hormone response elements (for steroids, T3, retinoic acid, peptides, etc) act as—or in conjunction with— enhancers or silencers (Chapter 43). Other processes that enhance or silence gene expression—such as the response to heat shock, heavy metals (Cd and Zn +), and some toxic chemicals (eg, dioxin)—are mediated through specific regulatory elements. Tissue-specific expression of genes (eg, the albumin gene in liver, the hemoglobin gene in reticulocytes) is also mediated by specific DNA sequences. 

Figure 39-11. Location of hormone response elements (HREs) A, B, and C using the reporter gene-transfection approach. A family of reporter genes, constructed as described in Figure 39-10, can be transfected individually into a recipient cell. By analyzing when certain hormone responses are lost in comparison to the 5 deletion, specific hormone-responsive elements can be located.

The presence of other factors within the cell that are necessary for the hormone response. 

Table 43-1. The DNA sequences of several hormone response elements (HREs). ...

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

Several Hormone Response Elements (HREs) Have Been Defined... 

Hormone response elements resemble enhancer elements in that they are not strictly dependent on position and location. They generally are found within a few hundred nucleotides upstream (50 of the transcrip-... 

Lucas P, Granner D Hormone response domains in gene transcription. Annu Rev Biochem 1992 61 1131. 

KONTESSIS P, JONES S, DODDS R, TREVISAN R, NOSADINI R, FIORETTO P, BORSATO M, SACERDOTI D and viBERTi G (1990) Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins. Kidney Int. 38 (1) 136-44. 

Johnston R.E. (1998). Pheromones, the vomeronasal system and communication — from hormonal responses to individual recognition. Ann NY Acad Sci 855, 333-348. 

Cortisol An adrenal gland hormone responsible for maintaining homeostasis of carbohydrate, protein, and fat metabolism. 

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