For such tissues (prostale), dihydmtestosterone is the final hormone and testosterone is the

rmed. The RLC eventually causes opening up of channels in the cell membrane (fig. 1.1.2) entry of various ions within the cell biological effects. The receptors of these hormones contain an enzyme lyrosine kinase incorporated within them. The RLC formation causes phosphorylation of the protein tyrosine kinase which leads to the final biological effects [There are strong evidences to suspect that the enzymes having tyrosine kinase activty are involved in growth as well as cancer formation]. WHEN THE R IS IN THE CYTOSOL OR IN THE NUCLEUS (Steroid hormones) Events are as follows : 1. The receptors (R) are present within the cytosol. 2. The R has a special domain called "DNA binding domain" which contains Zn++. 3. The steroid hormone molecules [recall, all steroid hormones conlain a CPP ring structure; being lipid, all steroid hormone molecules can pass through the cell membrane by 'lipid diffusibility', (chap 1 sec I), because cell membrane itself is oily in nature. Also compare this phenomenon with that seen with peptide hormones : peptide hormones cannot cross the cell membrane. Therefore, their receptors must be present in the cell membrane to suit the concept of teleology] enter the cytosol by crossing the cell membrane. 4. The ligand (L), ie, the steroid hormone molecule now binds with the R and RLC is formed. 5. Formation of the RLC causes the DNA binding domain of the R to expose itself fully and to become active. 6. The RLC moves to the nucleus (therefore, these receplors are also called mobile receptors) and the DNA binding domain gets itself attached to a specific region of a specific DNA (this portion of the DNA is called 'enhancer') 7. This attachment with the DNA binding domain and enhancer causes the enhancer to become active and increased transcription of messenger RNA (mRNA) occurs. 8. These mRNAS, in turn, increases the synthesis of their corresponding proteins, which can be either enzymes or structural proteins. The enzymes also can be either degrading enzymes or synthetic enzymes. 9. Now, the biological effect (s) occurs. Eg : Cortisol (steroid hormone) increase in synlhesis oftransminase degradation of amino acids and enhancement of gluconeogenesis. N.B : (i) Sleps 7 and 8, taken together constitute genetic expression. Therefore, the popular phrase, 'the steroid hormone acts by regulating genetic expression' should now be clear. They say regulating (not increasing) because, the genetic expression, with some ligands may be inhibited (instead of accelerated) too. (ii) estrogen and thyroid (recall, thyroid is not a steroid hormone) receptors are also situated within the cell, but these Rs are situated right on the nucleus (not in the cytosol). However, otherwise, estrogen and thyroid hormones behave similarly with the corticosteroids (iii) studies suggest that the DNA binding domain of the R might have strong intrinsic affinily to combine with the enhancer. It is because of the presence of the rest of the R, this intrinsic affinity (to unite with the enhancer) is kept inhibited. The combination of the hormone molecule with the receplor causes withdrawal of this inhibitory effect and the DNA binding domain becomes free to combine with the enhancers. (iv) Sleroid receptors are often, for obvious reasons, called 'gene active' receptors. HORMONE SYNTHESIS GENERAL PRINCIPLES Peptide hormones. In short, peptide hormones are synthesized just as other prolein molecules are. Therefore, from DNA the mRNA (messenger RNA) is transcribed the corresponding peptide hormone produced (for details see protein synthesis, chap 12 sec VII). The special points for peptide hormone synthesis can now be noted 1 Within the cell of the endocrmal gland the peptide molecule prepared first, is usually a much bigger (bigger than the matured peptide hormone molecule) molecule and is called 'preprohormone'. Thus, we have preprohormone for insulin called, preproinsulin. 2. The preprohormone is decimated, a portion, usually called signal sequence, is removed What remains is called a prohormone leg. Preproinsulin proinsulin, chap.6, sec VI). 3. Prohormone is further decimated and a mature hormone molecule is released into the blood. ( However, sometimes, little prohormone may also escape into the blood, see insulin synthesis chap 6 sec VI. These pro hormones of blood have clinical importance, see chap 6, sec VI). This is not the end of the story. Some so called mature hormones may again be further allered at the cellular level and this altered molecule may be the final active agent. Thus, the so called mature hormone, testosterone, in some tissues (eg. proslate) is converted into dihydrotestosterone. For such tissues (prostale), dihydmtestosterone is the final hormone and testosterone is the prohormone. Steroid hormones. Only the salient features will be outlined. The steroid hormone synthesizing cells (eg, cells of the zona glomerulosa or fasciculata of suprarenal cortex) have LDL (low density lipoproteins, LDL conlain cholesterol) receplors. LDL molecules (see chap 8 sec VIII) of the blood plasma get attached with these LDL receptors cholesterol of LDL crosses the cell membrane enters the biosynthetic pathway of steroid hormone synthesis (= steroidogenesis), eg, cholesterol cortisol or aldosterone. Alternatively, steroidogenesis may start from a cholesterol molecule which has been synthesized from active acetate by the cell itself; but this is less preferred. The rate limiting step is the conversion of cholesterol (C27 structure) to pregnanelone (C21 structure) by the enzyme desmolase (table 6.4.1). Once formed, the steroid hor