I.	Removal of Milk

	1.	Nursing

		A.	Intervals=Species differences
			a.	Kangaroo=Continuous
			b.	Whale, Dolphin=30 min
			c.	Pig=1 hour
			d.	Human=2 hour
			e.	Cow=4-6 hour
			f.	Rabbit=1X/day
			g.	Tree Shrew=1X/2 days
			h.	Seal=1X/week
		B.	Milk ejection can occur under water
			--Marine mammals, Hippopotamus

	2.	Dairy Industry

		A.	Mechanical or Hand Removal
		B.	2X/day is historical
			--Still most common
		C.	3X and 4X a day is becoming more common
			--Especially in large commercial operations

	3.	Streak Canal

		A.	Must be open to remove milk
		B.	Methods
			a.	Negative Pressure
				--Milking Machine
				--Some Positive Pressure too
			b.	Positive Pressure
				--Hand Milking
			c.	Positive and Negative Pressure
				--Suckling

	4.	Absence of Milk Ejection

		A.	Passive Removal
		B.	Small amounts can be obtained from the teat 
			and gland cisterns, and large ducts
		
II.	Milk Ejection Reflex

	1.	Neuroendocrine Reflex

		A.	Afferent
			a.	Neural
		B.	Efferent
			a.	Endocrine	

	2.	Afferent Pathway

		A.	Teat
			a.	Greatest innervation
			b.	Pressure sensitive receptors in the dermis
				i.	Transform to Nerve impulse
		B.	Impulse travels via spinothalamic nerve tract 
			to Brain
		C.	Brain
			a.	Nerves synapse at hypothalamus
				i.	Paraventricular nuclei (PVN)
				ii.	Supraoptic nuclei (SON)

	3.	Hypothalamic Nuclei and Oxytocin Synthesis

		A.	PVN and SON synthesize oxytocin precursor
			a.	Package into vesicles
			b.	Precursor = oxytocin + neurophysin
			c.	Neurophysin is the carrier peptide 
				for oxytocin
			d.	Cleaved inside vesicle by proteolytic enzymes
			e.	Oxytocin = 9 amino acid peptide
			f.	Oxytocin bound to neurophysin 
				is storage form
		B.	Transport to Posterior Pituitary
			a.	Vesicles transported via axons
				i.	Travel from nuclei (Cell bodies) 
					through pituitary stalk
					to Neurohypophysis 
					(Posterior Pituitary)
				ii.	Hypothalamo-neurohypophysial tract
			b.	Oxytocin-Neurophysin stored in neurosecretory granules
				at terminal ends of Axon
				i.	Herring bodies
		C.	Synthesis and Transport not part 
			of Milk Ejection Reflex
			a.	Impulse at SON and PVN cause action potential
				down Hypothalamo-neurohypophyseal tract 
				axons to posterior pituitary
			b.	Cause release of oxytocin and neurophysin
				i.	Neurophysin is no longer bound 
					to oxytocin
				ii.	Start of efferent pathway
	
	4.	Efferent Pathway


		A.	Efferent pathways starts with release 
			of oxytocin into blood
		B.	Oxytocin travels to the mammary gland
		C.	Binds to oxytocin receptors on myoepithelial cells
			a.	Oxytocin receptors are not found 
				on mammary smooth muscle
			b.	Receptors increase during gestation 
				and remain constant during lactation
		D.	Myoepithelial cells contract
			a.	Intraluminal pressure increases
			b.	Causes Milk ejection
	
III.	Oxytocin Surge

	1.	Udder stimulation

		A.	Blood oxytocin is normally increased within 
			1-2 minutes after udder stimulation
		B.	Hygiene
			a.	Cleaning the udder stimulates milk ejection
		C.	Manual stimulated vs. nonstimulated 
						(Milkers straight on)
			a.	Manual stimulation
				i.	Shorter milking time (efficiency)
				ii.	Higher milk flow rates
			b.	Peak blood oxytocin was not different
				i.	Occurred 3 minutes latter
		D.	Length of stimulation
			a.	Increased stimulation time
				i.	Increase in flow rate
				ii.	Decreased milking machine time
			b.	Total time was not different 

	2.	Timing

		A.	Timing of Oxytocin release relative to milk removal 
			is an important factor affecting milk ejection
		B.	Oxytocin has a very short half life in blood
			a.	0.55 to 3.6 minutes

	3.	Sensitivity

		A.	Sensitivity of neuroendocrine reflex decreases 
			as lactation progresses
			a.	Oxytocin peaks decline
		B.	Dry period may serve to restore sensitivity
		C.	Oxytocin receptors on myoepithelial cells 
			can respond to very low levels of oxytocin

IV.	Other roles of Oxytocin

	1.	Parturition

		A.	Oxytocin also causes ejection of the fetus 
			and placenta
			a.	Increases uterine contractions
		B.	Same oxytocin will stimulate milk letdown
			a.	Most mammals will leak milk around the 
				time of parturition

	2.	Maternal Behavior

		A.	Injections of oxytocin stimulate maternal behavior 
			in rats

	3.	Lipogenic

		A.	Has insulin-like activity
		B.	Lipids need to be made to replace those lost 
			in milk

	4.	Osmoregulator

		A.	Structurally, oxytocin is very similar to 
			antidiuretic hormone (ADH)
		B.	Water loss through milk, needs to be conserved 
			by kidney

	5.	Autonomic Regulation

		A.	Oxytocin containing neurons also go other regions 
			in brain besides pituitary
		B.	Autonomic regions
			a.	May be involved autonomic control
				 such as cardiovascular effects

	6.	Prolactin Release

		A.	May be involved
		B.	Evidence inconclusive

V.	Other Mechanisms of Milk Ejection

	1.	Antidiuretic Hormone
		A.	1/5 Oxytocin activity
	2.	Visual or Auditory
		A.	A conditioned reflex
		B.	Stimulates oxytocin
	3.	Stimulation of the Genital Tract
		A.	Primarily Vaginal Distention
		B.	Stimulates Oxytocin
	4.	Mechanical Tap Stimulus
		A.	Kneading or butting of udder 
			by young elicits response
		B.	Does not involve oxytocin
		C.	Occurs under anesthesia or denervation
		D.	Not inhibited by epinephrine
		E.	Local response
		
VI.	Involvement of Autonomic Nervous System and Stress

	1.	Parasympathetic

		A.	No parasympathetic innervation of mammary gland

	2.	Sympathetic

		A.	Involves Epinephrine and Norepinephrine
			a.	Produced by Adrenal Medulla
			b.	Norepinephrine is neurotransmitter 
				for postganglionic sympathetic nerves
		B.	Two types of receptors
			a.	Alpha
			b.	Beta
		C.	Alpha receptors
			a.	Vasoconstrictive
				I.	Decrease mammary blood flow
			b.	In brain, stimulate milk ejection
				I.	Norepinephrine
		D.	Beta receptors
			a.	In brain, inhibit milk ejection
		E.	Location of receptors very important
	
	3.	No direct innervation of alveoli or myoepithelial

		A.	Innervation is arterial
			a.	Lower blood flow when stimulated
		B.	Norepinephrine and epinephrine inhibit 
			oxytocin-induced contraction of myoepithelial cells
			a.	Adrenal source rather than neural

	4.	Stress

		A.	Stress inhibits milk ejections
			a.	Epinephrine and Norepinephrine from Adrenal 
				or Sympathetic nerve
		B.	Effects
			a.	Decrease blood flow
			b.	Reduce myoepithelial cell contraction
			c.	Reduce oxytocin from pituitary

		C.	Norepinephrine is more important than epinephrine 
			in cattle
		D.	Emotional disturbances can inhibit CNS part 
			of milk ejection reflex
			a.	Oxytocin injections needed 
				to cause milk letdown
				i.	Used in first calf heifers 
					to remove milk until 
					they are used to being milked
				ii.	Lack of milk removal would decrease 
					yield during lactation

VII.	Residual Milk

	1.	15-25% of total milk in udder at start of milking 
		is not removed
	2.	Can be removed by oxytocin
		A.	Usually not a management practice
	3.	Factors effecting amount of residual milk
		A.	Age
			a.	Increases with lactation number
		B.	Decreases in proportion to milk yield
		C.	Less with more frequent milkings
		C.	Machine-milked less than Hand-milked