Quiz 3 Flashcards
Hormones
Organic chemicals secreted into blood by ductless glands
Hormones are secreted as a result of various internal and/or external stimuli
Hormones bind to specific cell receptors which have a high affinity for the molecule
Protein Hormones
Molecularly large, water soluble, and short acting
Can not diffuse across the cell membrane
Steroid Hormones
Molecularly Small, fat soluble, and long acting
Can diffuse across cell membrane
Two classes of cell-surface receptors
G-protein linked receptors
Enzyme linked receptors
When does mammary growth and develop occur
Continuously throughout life
Morphogenesis
The formation and differentiation of tissues and organs
Mammogenesis
The formation and differentiation of the mammary gland
Mammary Growth
An increase in size or an increase in number
Hypertrophy - increase in size
Hyperplasia - increase in number
Mammary Development
A less specialized structure becoming more specialized and/or, A change in function
Ectoderm
embryonic skin, gives rise to mammary epithelium (parenchyma)
Will be functional portion of gland
Mesoderm
gives rise to mammary stromal tissues
Main function is support
Areolar, fibrous, and elastic connective tissues
Adipose (fat) tissue
Nerves
Blood and lymph vessels
Mammary Fat Pad
Derived from mesoderm (mesenchyme)
Stroma
Connective tissue
Not glandular
“supportive function”
Ontogeny
Ventral ectoderm is in the process of thickening
Embryonic Growth and Development
Band is formed as thickening of ectoderm, interiorly only, around day 32
Bud is formed by day 43 as an inward growth of the ectoderm
Mammary Line
Definite orientation of epithelial cells proliferating along a straight line in a confined area
Accounts for linear arrangement of teats
~35d embryo in bovine
Dairy cattle have two mammary lines, one on left and the other on the right
One mammary band results in two mammary buds
Mammary Bud
Differences between male and female mammary development noted at this time
Sexual dimorphism
After this stage, embryo called a fetus
~43 d embryo in bovine
Supernumerary Teats
Derived from embryonic mammary buds
Why do some male species of mammals not have teats
Fetal Testosterone pinches off the neck of the bud resulting in no teat development
Fetus
reserved for eutherians
At the same time embryo called fetus in placental mammals:
- Incubation period over for monotremes; hatching
- Pregnancy over for marsupials; pouch time
Fetal Growth and Development
Early Teat Formation
Primary Sprout
Secondary Sprouts
Canalization of Primart Sprout
Development of teat and gland cistern
Development of MSL
Fetal Teat Formation
Rapid proliferation of mesenchymal cells forces the bud downward ventrally
Primary Sprout
- “If the sprout should fail to develop it is believed that quarter of the cow’s udder would lack all glandular development” – Turner, 1930
He was right; primary sprout is destined to become a teat opening and is called a galactophore
Galactophore
Variation in galactophore number per teat coincides with number of teat opening
Canalization of Primary Sprout
Initially primary sprouts are solid cords of cells
Eventually, cells in center disappear to form luminal (hollow) spaces
○ Apoptosis
○ Cell migration
Forms eventual teat and gland cisterns
Secondary Sprouts
- Primary sprout sends out secondary sprouts
- Entire future development of the secretory and storage tissue centers around these structures
- Secondary sprouts will become large milk ducts that lead into the gland cistern
Streak Canal Formation
As the teat develops the tip invaginates from the outside so the surface epithelium becomes keratinized
Why is there no hair on the teats?
The hair buds did not develop in the fetal stage
No hair helps prevent bacterial colonization
What is the importance of the mammary fat pad?
Very early in fetal life, female develops a more extensive fat pad than the male
Male fetus has scrotal development instead
Fat pad has no room to expand in male fetus
Limits mammary growth in males
What happens to the MFP as the fetus grows
Fat pads become larger
Further branching of secondary sprouts
Median suspensory ligament becomes more prominent
When does puberty occur in Holstein heifers
9-11 months
45-50% of mature BW
Estrogen in Pubertal Mammary Growth
isometric ductal growth
Think: lengthening
Progesterone in Pubertal Mammary Growth
isometric lobular growth
Think: branching
Mammary Estrogen Receptors
Located mainly in nuclei of mammary epithelial cells (MEC)
Most proliferating cells are estrogen-receptor negative
Receptor positive cells release growth factors such as EGF and IGF-I, which causes proliferation through paracrine signalling
Mammary Progesterone Receptors
Located mainly in nuclei of mammary epithelial cells (MEC)
Most proliferating cells are progesterone-receptor negative
Receptor positive cells release Wnt-4, which causes proliferation through paracrine signalling
When is mammary growth and development most rapid?
Mammary growth occurs in spurts around when P and E are equivalent around estrus - synergy between the two causes mammary growth spurts
What is the role of Growth Hormone
Mammary epithelial cells apparently lack GH receptors
○ Yet, GH promotes mammary duct growth
○ Stromal cells in the mammary fat pad seem to have GH receptors
§ So GH effects likely through mechanism involving IGF-I
Another example of paracrine mechanisms in mammary development
Mammogenesis during gestation
- Quantitatively, most mammary growth and development occurs here
- Highlights
○ Ovaries remain active
§ Progesterone and estrogen produced
○ Estrogen and progesterone synergy (“ 1 + 1 = 3”)
○ Allometric growth of ducts (much lengthening and branching)
○ Cellular mechanisms for E2 and P4 thought to be the same as in pubertal example; just increased rate
○ Fat pad almost completely remodeled
No true alveoli until late gestation
Lactogenesis I
4-6 Weeks before parturition
Cellular and enzymatic differentiation of mammary epithelial cells
Very limited milk secretion ability
Lactogenesis II
About 2 days before calving
Hours immediately before parturition, extending through several days postpartum
Copious secretion of all milk components
At the end of Stage II there are alveoli present and the ability to enter lactation is there
Where do alveoli comr from
The differenciate from existing epithelial cells in the udder
What is Lactogenesis
A hormone driven process
We will explore lactogenic effects of:
○ E2
○ P4
○ Cortisol
○ Prolactin
Know that other hormones and growth factors are involved too
Glucocorticocoids in Lactogenesis
*Cortisol receptors are in mammary epithelial cells
* Cortisol activation induces differentiation of RER and Golgi
*These organelles areespecially important for protein and lactose and fat synthesis
*Cortisol also facilitates tight junction formation between cells
Prolactin
Surge in Stage II lactogenesis plays a major role in activating milk protein gene receptor.
Hypophysectomy
Removal of anterior pituitary
causes cessation of milk synthesis in ruminants and lab animals
removes source of all pituitary hormones
causes depression of key enzymes (proteins) needed tosynthesize caseins, fats and lactose
Prolactin, Adrenocorticotropin Hormone, Somatotropin Hormone and Thyroid Stimulating Hormone restore mil synthesis
Timing of Prolactin effect on Milk Yield
Prolactin has a delayed effect on increasing milk yield
Lactigenic Hormones
Maintain Lactation
Cortisol and Prolactin
Stopping milking goes stops release of these hormones
Galactopoesis
Galactopoesis: enhancement of established lactation
Galactopoesis direct effect
Acts directly on mammary tissue
Galactopoesis indirect effect
indirect effect on metabolism affecting
supply of precursors for milk synthesis
GH (STH, BST)
increases milk yield
action:
*increases IGF 1; increases protein synthesis
*increases blood flow/nutrients to mammary gland
*antagonistic to insulin
Affects of BST
GH Increases catabolism of fatty acids, glycogen (lipolysis, glycogenolysis)
increases gluconeogenesis
increases blood glucose
increases efficiency of production (greater lbs. of milk/lb. DMI)
Significance of Lactose
Responsible for drawing 80% of the water in milk into the lumen
Why is the Mammary Gland different than most other organs?
It offers no specific advantage to the animal (dam)
It exerts a tremendous physiological demand on the animal (dam)
It gets a high priority for nutrients; even at the expense of the health of the animal (dam)
- This is not a concern in a well-managed cow
Metabolic Changes for Mammary Function
Induces an increase in metabolic rate
Demands increased blood flow (400-500 units blood/unit milk)
Demands increased nutrient supply
An inability to accommodate demands will result in metabolic disorder(milk fever (hypocalcemia), ketosis (hypoglycemia))
Difference in Sugar concentration between blood and milk
90 times more sugar in milk
Difference in fat concentration between blood and milk
9 times more fat in milk
Difference in protein concentration between blood and milk
0.5 times protein in milk
(More in Blood than milk)
Difference in calcium concentration between blood and milk
13 times more calcium in milk
Difference in phosphorus concentration between blood and milk
10 times more P in milk
Difference in sodium concentration between blood and milk
0.15 times
Milk component precursors
Glucose
Amino acids
Acetate
Butyrate
Triglycerides and free fatty acids
Proprionate
3 Carbon VFA
Produced in the Rumen
Goes to Liver for Gluconeogenesis
Glucose
Used Primarily for Lactose Synthesis
Very Little stored as glycogen
Very Little used for fatty acid synthesis
Very little diverted to Acetyl-CoA for Krebs
Mammary Gland Glucose Utilization
Mammary Gland utilizes 60-85% of circulating blood glucose
60-70% of glucose taken up by the cell is used for lactose synthesis
Some glucose is converted to UDP galactose
20-30% used for pentose phosphate pathway
Lactose Synthesis
Occurs in the Golgi Apparatus
Relies on Lactose Synthetase
UDP Galactose + Glucose
Lactose Synthetase
Enzyme responsible for synthesizing lactose
Galactosyl Transferase + alpha-lactalbumin
Lactase
Gut enzyme necessary to cleave lactose into smaller sugars for gut absorbtion
