Endocrinology, lecture on Receptor 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 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®E-Ra and  T ®A-R,
					        F/B ®G-R

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

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

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

			b. or heterologous

				i. nuclear:   E2®P-R

				ii. membrane: FSH ®LH-R ,  F/B ®I-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

X. Hypothalamo-Hypophysial Communication