I. 	Initiation of Lactation

	1.	Lactogenesis 
		A.	A process of mammary alveolar cell differentiation 
		B.	Conversion of non-secretory to secretory state


	2.	Two stage mechanisms or process
		A.	Cytologic and enzymatic differentiation 
			of the alveolar cells
		B.	Copious secretion of milk components into 
			the alveoli lumens


	3.	Late pregnancy
		A.	Mammary gland develops capacity to make milk
			a.	Small volume
		B.	Copious milk secretion does not take place 
			until near parturition

	4.	Milk components
		A.	Secretory cells before parturition can secrete 
			caseins and milk fat
		B.	Lactose synthesis is the key to the secretion 
			of large volumes of milk

II.	Cellular changes 
	
	1.	Prelactating alveolar epithelial cells
		A.	Irregular shaped nuclei
		B.	Minimal RER
		C.	Small Golgi
		D.	Few microvilli on apical surface
		E.	Few mitochondria
		F.	One or two lipid droplets

	2.	Changes at parturition
		A.	Hypertrophy of RER and Golgi
		B.	Appearance of large vesicles containing casein
		C.	Release of casein into the lumen
		D.	Increase in cytoplasmic fat droplets 
			and their lumenal release
		E.	Increase in microvilli on apical surface
		F.	Increase in number of mitochondria
		G.	Cell polarity
			a.	RER and nucleus moves to basal half of cell
			b.	Golgi are apical of nucleus
	

III.	Hormonal control of Lactogenesis

	1.	Lactogenic Complex

		A.	A combination of hormones controls lactogenesis 
			rather than one hormone
			a.	Species variation
		B.	Much information comes from in vitro studies
		
	2.	Progesterone

		A.	Key negative regulator of lactogenesis
			a.	Suppresses onset of synthesis of lactose, 
				alpha-lactoalbumin, and casein
			b.	Suppresses PRL induction of these 
				above components
				i.	Increases mammary threshold for PRL
				ii.	Inhibits secretion of PRL 
					from pituitary
			c.	Competes for glucocorticoid receptors
				i.	Has an affinity of glucocorticoid 
					receptors
		B.	Progesterone concentrations drop approximately 
			2 days before parturition
			a.	Negative effects are diminished

	3.	Insulin and/or IGF-I

		A.	Causes alveolar cell to undergo a cell division
			a.	Seems to be necessary for lactogenesis
			b.	IGF-I may actually be the primary mitogen 
				in vivo
		B.	Increase glucose uptake by cell
			a.	Stimulate glucose transporters
			b.	Needed precursor for lactose synthesis
		C.	May also increase expression of milk protein genes

	4.	Glucocorticoids

		A.	Stimulated by ACTH
		B.	Involved in development of RER and other changes needed 
			for protein synthesis
		C.	Involved in transcription of casein 
			and alpha-lactoalbumin genes
		D.	Mammary glucocorticoid receptors increase late 
			in pregnancy 	

	5.	Prolactin

		A.	PRL may be responsible for switch 
			between 1st and 2nd stages of lactogenesis
			a.	Receptors and blood concentrations 
				increase at that time
		B.	Synergize with Insulin and Glucocorticoids
			a.	Transcription of casein and a-lactoalbumin
			b.	Translation of milk protein mRNA
			c.	Swelling of Golgi membranes
			d.	Milk secretion
		C.	Combinations studies (in vitro)
			a.	Insulin alone
				i.	Cells divide
				ii.	No cytological changes
			b.	Insulin + Glucocorticoid
				i.	Develop RER and Golgi
				ii.	Synthesize structural proteins
				iii.	Minimal synthesis of milk protein 
					and lactose
			c.	Insulin + PRL
				i.	Transcription of milk protein genes
				ii.	Minimal Protein synthesis
			d.	Insulin + Glucocorticoids + PRL
				i	All cytological and enzyme changes
				ii.	Minimal lactogenic complex
	
	6.	Estrogen
		
		A.	Indirectly involved with lactogenesis
			a.	Increase PRL receptors peripartum
			b.	Control PRL release from pituitary
		
	7.	Somatotropin

		A.	Probably no direct effects
			a.	No ST receptors in vitro
		B.	Actions through IGF-I
			a.	Somatomedin
			b.	Secreted by liver
		C.	May have PRL-like activity with elevated levels

	8.	Local Factors

		A.	There is also evidence that local factors 
			effect lactogenesis
		B.	These probably work through autocrine 
			or paracrine mechanisms

IV.	Artificial Induction of Lactation
	

	1.	Used when you can't get animals bred	
	2.	Classically high levels of E + P for several days
		A.	Never get lactation that you would 
			if animal was pregnant
		B.	High incidence of ovarian cysts
	3.	Better success has been reported when E+P 
		is followed by PRL and Glucocorticoid

V.	Extracellular Matrix

	A.	ECM defined as the noncellular components of tissues (stroma)
	B.	Make up the basement membrane
		a.	Collagen, Laminin, and proteoglycans
	C.	Cell to Basement membrane anchorage needed for cells 
		to develop polarity and cellular orientation
		a.	Polarity and orientation needed 
			for maximal lactogenesis