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. á 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 á mRNA half-life (eg. E2, F, T3)


				i. á 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