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 Osmo-Pressure Balance Reproductive Endocrinology Prolactin Somatic Axis

Growth Factors Immune System Ca++, PO4 Homeostasis Pancreatic Hormones GI Hormones

Guts 'n Brains Brain Hormones Neurosteroids Neuropeptides Evolution

Figures for Endocrionology text:Vertebrate Endocrinology5th Edition - David O. Norris: Read pages 52-61 for this lecture acronyms    end

IX. Receptor Regulation 	


	A. receptors are proteins produced in the same way hormones


		1. instead of being exocytosed they are
		   incorporated into the membrane	 
								

			a. steroid production is also stimulated by protein synthesis: 
			   enzymes which have their effect in mitochondria and sER


	B. Receptors may be changed either quantitatively or qualitatively


	C. Up-regulation of hormone receptors


		1. creating more receptor molecules (quantitative)


			a. stimulated by hormones and other factors inducing 
			    transcription of immediate-early genes


			b. homologous:


				i. nuclear: E2®áE-Ra and  T ®áA-R,
					        F/B ®áG-R

					(1) may be tissue specific
					
						(a) E2®áE-Ra in uterus
						    E2®¯E-Ra in liver
							

				ii. membrane: PrL ®áPrL-R,  EGF ®áEGF-R


					(1) pulsatile hormone secretion may be  
						 necessary for receptor maintenance


			b. or heterologous


				i. nuclear:   E2®áP-R


				ii. membrane: FSH ®áLH-R ,  F/B ®áI-R  


		2. Hormone Binding Site Changes (qualitative)


			a. binding may increase the affinity for the hormone


				i. nuclear receptors
				
				
		3. Effector Site Changes


			a. phosphorylation of membrane receptors with
			   tyrosine kinase activity


			b. binding to nuclear receptor increases
			   affinity for HRE on the DNA		
			   
			   
	D. down-regulation


		1. homologous:


			a. nuclear: P ®¯ P-R,
				 F/B®¯G-R(may be tissue specific)


			b. membrane: Insulin ®¯ I-R, Epi ®¯ b-adreno-R


				i. GnRH administered continuously ®¯ GnRH-R
					

					(1) pulsatility maintains [receptor]


		2. heterologous:


			a. membrane: P-R and I-R by P


			b. nuclear:  T ®¯ E-R 


		3. long or short-term down-regulation by endocytosis


			a. receptors move through the membrane fairly rapidly


			b. -R concentration in membrane area


				i. cluster in coated pits


			c. recycled or degraded


		4. shorter term down regulation by desensitization


			a. phosphorylation or Gbg


				i. e.g. PKC phosphorylation of
				   I-R, EGF-R or b-adreno-R
				   reduces binding affinity for
				   Insulin, EGF or Epi respectively


		5. Hormone Binding Site Changes


			a. affinity for the hormone may be decreased


				i. negative cooperativity

				ii. pH

				iii. intracellular [GTP] or [Gbg]

				iv. [hsp 90] 


		6. majority of reduced cellular responses 
		
		   (tachyphylaxis, refractoriness, tolerance, desensitization) 
		   tachy=rapid  phylaxis=guarding - ¯ response w/multiple admin. of hormone over a short period
		   
		   due to down-regulation