Endocrinology, lecture on Hormone Synthesis
USD Department of Biology
Endocrinology
Summers
Hormones
Endocrine Glands
Receptors
Homeostasis
2nd Messengers
Nuclear Receptors
Genetic Regulation
Hormone Synthesis
Receptor Regulation
Hypothalamo-Hypophysial Communication
Tropic Hormones
Neurohypophysial Nonapeptides
Thyroid Axis
Steroids
Adrenal Axis
Adrenal Medulla
Osmotic-Pressure Balance
Reproductive Endocrinology
Prolactin
Somatic Axis
Growth Factors
Immune Factors
Ca++, PO4 Homeostasis
Pancreatic Hormones
GI Hormones
Guts 'n Brains
Brain Hormones
Neurosteroids
Neuropeptides
Endocrine Evolution
Figures for Endocrionology
text:Vertebrate Endocrinology5th Edition - David O. Norris:
Read pages 52-61 for this lecture
acronyms    end
VIII. Mechanisms of Action - Hormone Synthesis  	


	A. Hormones affect protein synthesis via HREs by 
	   stimulating transcription and enzyme activation


		1. some of the proteins synthesized are hormones


			a. some are enzymes which are important in steroid, 
			   monoamine, or thyroid hormone synthesis


				(1) peptides too


	B. Transcription activation


		1. RNA Polymerase activity


			a.  enzyme (polymerase) molecule number


				i. mediated by transcription and translation


			b. activating existing enzyme (not phosphorylation)


				i. basal transcription factors


		2. mRNA stability


			a. mRNA accumulation follows RNA polymerase activation


			b. hormones may  mRNA half-life (eg. E2, F, T3)


				i.  effective translation


					(1) glucagon ¯ mRNA half-life


		3. Specificity - Template activity


			a. Which genes are transcribed - HREs present


			b. DNA sensitivity


				i. condensed DNA is less sensitive to DNAse


				ii. unwound DNA necessary for transcription


					(1) specific genes are made available for receptor binding


						(a) Hormone/receptor complex may unwind DNA
						   by sliding along or by configurational change
						   due to binding to HRE


				iii. once available, 2nd transcription induction may occur
				     more quickly = memory effect


					(1) 2nd hormone (eg. E2) dose more effective than the first


						(a) also by up-regulating receptor


			c. DNA Methylation		(CH3 = methyl group)


				i. methylation of cytosine at the 5 position
				    may repress gene activation

					(1) methylation enhances DNA curvature


				ii. hormones may actively demethylate specific genes

					(1) helps unwind DNA


				iii. hormones or other transcription factors bound 
				      to active genes prevent methylation


					(1) after hormone withdrawl the demethylated site
					   is not immediately remethylated
					   ® involved in the memory effect


	C. RNA processing and translation
			

		1. the gene coding for the hormone includes exons (coding 
		   for amino acid sequences) intersperced with introns


		2. introns are removed from the primary transcript so mRNA  
		    includes only codes for peptide and signal sequence


		3. translation begins on a free ribosome and transferred 
		   to the endoplasmic reticulum (rER)				


			a. signal sequence interacts with signal recognition particle


			b. SRP binds to SRP receptor on the ER


		4. translated peptide + signal sequence = preprohormone


			a. moved into the ER lumen by chaperonins/foldases or hsp


				i. signal peptide cleaved from the N-terminal by protease
				   on cisternal (inside) membrane surface


					(1) prohormone

						(a) half-life of preprohormone is short

			b. steroid production is also stimulated by protein synthesis: 
			   enzymes which have their effect in mitochondria and sER
			   
		5. ER is transitional to Golgi


			a. prohormone packaged into vesicle


				i. prohormone cleaved to hormone by protease

					(1) if necessary


		6. hormone released by exocytosis (vesicle fuses to cell membrane)
		
			a. Ca++ dependent

IX. Receptor Regulation