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 86-93 for this lecture acronyms    end

VII. Mechanisms of Action/Genetic Regulation  		


	A. Hormone Regulation of Gene Transcription


		1. the essential mechanism of steroid and thyroid hormones
			plus 2nd messenger TFs like CREB


			a. regulate 10 - 1,000 genes in a given target cell


		2. T3/steroids/CREB modify protein synthesis by affecting mRNA synthesis


			a. Increased RNA polymerase activity & transcription
			

				i. by affecting configurational change of DNA


				ii. or by sliding along DNA to transcriptional site


				iii. probably not by activating/phosphorylating
					 RNA polymerase itself


		3. activation of Promoter and Enhancer regions of hormone regulated genes 


			a. hormone/receptor complex binds to DNA segements called
			   Hormone Response Elements (HRE)              							         


				i. specific enhancer and promoter elements


					(1) high affinity + specifies which genes
						are transcribed


						(a) receptor alone will bind
						    if hsp 90 is removed


					(2) necessary for gene transcription


				ii. present in more than one copy


				iii. related HRE sequences on DNA
				    for different steroids/T3/2nd mess TFs


	B. Immediate-Early Genes Oncogenes and Proto-oncogenes


		1. stimulated by receptors of steroid and thyroid 
			hormones or 2nd messenger TFs binding HREs


			a.  PKA/CREB + CBP/CRE; PKC; STAT dimer; MAP K + TF

		
		2. negative/inhibitory HREs
		
		
			a. hormones may inhibit immediate-early genes


				i. glucocorticoids (B/F) bind nGRE and inhibit myc


		3. control production of growth factors, hormones, membrane
			and DNA-binding receptors, G proteins, and protein kinases
				
				
			a. ras immediate-early gene codes for subunits of G proteins,
				sos codes for 2nd messenger protein;
				raf1 is a PK


			b. fos for cell division & hormone production
				    (adrenal axis hormones)


			c. sis for growth factor production


			d. myc for cell division

								
		4. products of immediate-early genes may interact


			a. PDGF from  sis  stimulates  fos

				
		5. immediate-early genes are also called proto-oncogenes because
		    they share homology with sequences of DNA expressed in
			cancers (oncogenes)


			a. oncogenes stimulate cell growth/tumor formation by 
			   controlling production of growth factors


				i. found in viruses (v-onc)