Endocrinology, lecture on Mechanisms of Action/Genetic Regulation
USD Department of Biology
Endocrine Glands
2nd Messengers
Nuclear Receptors
Genetic Regulation
Hormone Synthesis
Receptor Regulation
Hypothalamo-Hypophysial Communication
Tropic Hormones
Neurohypophysial Nonapeptides
Thyroid Axis
Adrenal Axis
Adrenal Medulla
Osmotic-Pressure Balance
Reproductive Endocrinology
Somatic Axis
Growth Factors
Immune Factors
Ca++, PO4 Homeostasis
Pancreatic Hormones
GI Hormones
Guts 'n Brains
Brain Hormones
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)

VIII. Hormone Synthesis