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 57-61 for this lecture acronyms    end

III. Target Tissues and Receptors  		


	A. Target tissue


		1. Any tissue for which there is a response stimulated by a specific endocrine


			a. requires receptor mediation


				i. each target tissue is a target tissue only if it has receptors
				   for the specific hormone 


				ii. e.g. FSH stimulates follicular growth in the ovaries; but if
				    the ovaries had no FSH receptors, or blocked FSH receptors,
					 FSH would have no effect



	B. Receptors


		1. location


			a. membrane receptors


				i. membrane proteins which are receptors for peptide hormones


					(1) + a few steroids


			b. cytosolic/nuclear receptors


				i. receptors for steroids may bind in the cytosol travel to
				   the nucleus and bind to the DNA


					(1) some types (e.g. glucocorticoid) are usually bound
					   and \ usually in the nucleus


				ii. thyroid and  some steroid (e.g. E2) receptors
				    are always nuclear 


				iii. bind to and mediate genetic activation


		2. Hormone receptors are specific binding proteins


			a. a receptor can bind a specific hormone, but not others


				i. agonists and antagonist of this hormone also bind to the receptor


				ii. binds to the receiving or recognition site of the receptor
				    (usually 1 site/receptor)


					(1) receptor also has effector site ® modifies cellular function


			b. a hormone may have several distinct specific receptors


				i. most neurohormones do


				ii. hormones have one (or many) 1o receptor, but may
				    bind, under certain conditions to the receptor of another hormone


					(1) eg. similar hormones at [high]


					(2) hormonal specificity is insured physiologically by
					   [hormone] (+ affinity)


				iii. function of some hormones depends upon binding to the
				     same receptors


					(1) NE and Epi


		3. Receptors intitiate change in cellular function


			a. bound receptors change intracellular function in 4 ways


				i. membrane receptors may be enzymes themselves


				ii. membrane receptors coupled with G proteins stimulate
				    enzymatic action via 2nd messengers


				iii. the receptor may be connected to or comprise an ion channel


				iv. cytosolic/nuclear receptors and 2nd messengers interact
				    with genes


			b. new hormonal molecules and reactivated receptors are necessary
			   for hormone action to continue


				i. binding is reversible (non-covalent)


				ii. receptor may be endocytosed and degraded or recycled


				iii. hormone is degraded enzymatically


					(1) enzyme may be in the blood, intercellular fluid or on the membrane


			c. Affinity


				i. tendency to bind and stay bound to the receptor


				ii. KD (dissociation constant) = 1/KA (affininty constant)
				
					(1) [hormonal] leading to 1/2-maximal receptor occupancy
					
					(2) ED50 is often lower  ([hormonal] leading to 1/2-maximal response)
					
					(3) different for different tissues

				iii. receptor specificity is functionally derived from high affinity


					(1) due to slow dissociation rate


				iv. non-specific binding