Dairy Science Quiz 3

hormones

Organic chemicals secreted into blood by ductless glands

These chemicals exert an action on target cells elsewhere in the body

Hormones are secreted as a result of...

various internal and/or external stimuli

(stimuli are mediated by neural or endocrine systems)

protein hormones

water soluble

short acting

steroid hormones

lipid soluble

long acting

Hormones bind to specific ___________ which have a high affinity for the molecule

cell receptors

How do peptide hormones work?

peptide acts as first messenger:

peptide binds to receptor on surface of target cell --> trigger enzymatic reactions in the cell, relays messages from extracellular peptide hormone enzymes and initiates a series of successive reactions in the cell

How do steroid hormones work?

enters the target cells and have a direct effect on the DNA of the nucleus

endocrine system

Glands secrete hormones that regulate processes such as growth, reproduction, and nutrient use (metabolism) by body cells.

bovine fetal development

- Series of cell migrations thickenings on ventral body surface

- Mammary Streak or Mammary Band

- Mammary Line (not past the umbilicus)

- Mammary Hillock/Mammary Bud

gestation month 1

conception

gestation month 2

band, line, hillock, streak, crest, bud

gestation month 3

teat ends more pointed, primary sprout and MFP

Reorganization not ____________, corresponds with each gland

proliferation

Sexual dimorphism in bovine fetal development

F elongated and ovoid

- proliferation resumes, increase, extension and elongation of the bud

- Mammary sprout

- Canalization of sprout

M mesenchyme is target of androgens

- condensation, restriction of superficial bud, some species no teats/nipple

Development prior to birth

external

internal

Development after birth until puberty

isometric growth

allometric growth

isometric growth

all body parts grow at the same rate

allometric growth

The variation in the relative rates of growth of various parts of the body, which helps shape the organism.

Development prior to pregnancy

- majority of tissue is adipose/connective

- some duct development, but no functioning alveoli

- alveolar development requires synchronous E2 +P4 stimulation (gestation)

Early Prepubertal Mammary Development Traditional View

Quiescent -

- waiting near puberty

- Some allometric development beginning ~5 mo

When does allometric development actually begin?

2/3 months

Post pubertal mammary gland changes timeline

- days 5 - 16; luteal phase (high P4)

- days 17 - 1; proestrus, estrous phase

- (high E2)

Post pubertal mammary gland changes

cyclic hormonal changes associated with the initiation of the estrous cycle

• point at which reproductive change begins to affect mammary function

• Allometric vs. Isometric growth

proestrus & estrus → E2 increases

• mitotic activity; duct growth

metestrus & diestrus → P4 increases

• alveolar differentiation

mammogenic

Affect on growth and development ofthe MG

• Ducts and luboloalveolar development

lactogenic

Promote structural and/or biochemical differentiation of alveolar epithelial cells to synthesize milk components

Galactopoietic

Maintain or enhance milk production once lactation is established

hormones supporting mammogenesis and lactogenesis

estrogen, progresterone, cortisol, alpha-lactalbumin

estrogen

(placenta, ovary) → mammary duct growth

progesterone

(CL, placenta) → alveolar differentiation

cortisol

(adrenal cortex) + prolactin (ant. pit.) → protein synthesis+ α-lactalbumin (RER)

alpha-lactalbumin

→ lactose synthesis (golgi apparatus)

1st and 2nd trimester mammary changes

synchronous E2, P4

• duct proliferation

• development of gland cistern

Allometric growth

2nd trimester mammary changes (in depth)

- secretory tissue develops; replaces adipose

- end buds form

- alveoli differentiate

- connective tissue support forms (lobules, lobes)

- tissue DNA increases 25%

- vascular, lymph vessels proliferate

3rd trimester mammary changes (in depth)

- Cell membranes proliferate

- Secretory activity initiated

- Lipid & secretory granules evident

- Mammary gland becomes distended

What does placental E2 and Luteal P4 do?

- duct development

- lobulo-alveolar development

- suppression of milk synthesis

- P4 suppresses α-lactalbumin and lactose synthesis

What does estrogen do?

- Stimulate mammary duct growth

- Prolactin release

- Synergize with progesterone and prolactin to stimulate protein synthesis and duct growth

- combined effect is greater than separate

What does progesterone do?

- stimulates lobulo-alveolar growth; synergizes with estrogen and prolactin

- retards milk synthesis

- retards synthesis of enzymes (α-lactalbumin) necessary for lactogenesis in the prepartum mammary gland

- does not significantly depress milk yield inlactating cows

- P4 + PRL stimulates amino acid incorporation into protein

Third trimester gestational development

- estrogen and progesterone increase, continuing support GH

- last month: lactogenesis stage 1

- last week/early postpartum: lactogenesis stage 2

lactogenesis

initiation of milk synthesis in the E2/P4"primed" mammary gland when:

• corpus luteum regresses

• P4 declines

• cortisol increases

• PRL, GH increase

(these circumstances occur at parturition)

How does P4 retard milk synthesis in the nonlactating mammary gland? (basics)

- P4 similar to cortisol in structure

- P4 blocks cortisol binding sites when no milk being secreted

How does P4 retard milk synthesis in the nonlactating mammary gland? (the details)

blocks glucocorticoid (cortisol) receptors

• cortisol + PRL stimulates synthesis of PRL receptors onmammary cells

blocks induction of PRL receptors

• retards synthesis of α-lactalbumin, casein mRNA

• retards casein, α-alactalbumin, lactose synthesis

Changes associated with declining P4:

- increased cortisol binding to mammary cells

- induction of PRL receptors

- increased α-lactalbumin, casein, enzyme synthesis

- results in increased lactose and protein synthesis

What does cortisol do?

- from adrenal cortex

- dexamethasone is synthetic cortisol

- Action

• synthesis stimulated by maternal, fetal ACTH

• essential to lactogenesis

- adrenalectomy → no lactogenesis

• cortisol potentiates action of PRL

Action of cortisol + PRL:

- increase PRL receptor synthesis

- increase RER- increase mRNA

- increase protein transcription/translation

- increase casein/α-lactalbumin/lactose synthesis

- cortisol is permissive to action of PRL

During established lactation:

- P4 will increase again during the luteal phase of the estrous cycle

- P4 will increase with conception

P4 has high affinity for milk fat globule thus...

- thus P4 will be sequestered by milk fat & exported from cell (cortisol will be free to bind to cell)

- milk synthesis unimpaired

From parturition to peak lactation (~ 60 days):

- DNA increases by ~ 65% by 10 days postpartum

- number cells/ alveolus increases

- mammary gland DNA peaks at peak lactation

- regression begins after peak lactation

- This growth relies upon continued endocrine support (PRL, GH, cortisol)

Hypophysectomy

removal of the anterior pituitary gland (hypophysis)

Hypophysectomy causes...

cessation of milk synthesis in ruminants and lab animals

• removes source of all pituitary hormones

• causes depression of key enzymes (proteins) needed to synthesize caseins, fats and lactose

________ + ________ + ________ + ________ restores milk synthesis

PRL + ACTH (cortisol) + STH + TSH restores milk synthesis

Anterior pituitary gland support

- ACTH --> adrenal cortex --> cortisol --> prolactin binding, protein synthesis

- PRL --> mammary cell protein synthesis

- TSH --> thyroid --> T3,T4 thyroxin --> cellular metabolism

milking stimulus increases

• PRL

• ACTH (cortisol)

• oxytocin

Is prolactin (PRL) an absolute requirement for full lactogenesis?

yes

Regulation of calcium metabolism

calcitonin, T3, T4, and parathyroid hormone

Calcitonin

acts on osteocytes → calcium absorption → decreases blood calcium

Parathyroid hormone

• acts on osteocytes → calcium resorption → increases blood calcium

• acts on kidney → depresses calcium excretion; stimulates vitamin D conversion → increases gut calcium uptake

resorption

the process of removing or digesting old bone tissue

Triiodothyronine (T3) and Thyroxine (T4)

• increase rate of cellular metabolism (BMR)

• increase cellular O2 consumption and energy production

• increase protein synthesis

• catabolic effect on metabolism (glycogenolytic, lipolytic)

• early lactation, increases yield 10%

• late lactation, increases yield 15 -20%

Thyroprotein

- increases yields ~ 2-4 months; then decline

- older, high-yielding cows respond best

- removal is followed by abrupt decline in yield

- fed only to cows in positive energy balance

- DMI increase is crucial

- increases PRL

- eventually lowers cortisol availability (increases CBG)

Growth hormone can act on...

liver, fat, bone, muscle, etc.

What does growth hormone do?

- increases protein synthesis

- affects metabolism (anabolic & catabolic)

- stimulates growth factors (IGF's from liver)

- synergizes with E2, P4, PRL

- anatagonistic to insulin (stimulates gluconeogenesis, lipolysis)

Galactopoesis:

enhancement of established lactation

• direct effect on mammary tissue

• indirect effect on metabolism affecting supply of precursors for milk synthesis

GH (STH, BST):

• increases IGF-1; increases protein synthesis

• increases bloodflow/nutrients to mammary gland

• antagonistic to insulin

• GH Increases catabolism of fatty acids, glycogen (lipolysis, glycogenolysis)

• increases gluconeogenesis

• increases blood glucose

• increases efficiency of production (greater lbs. of milk/ lb. DMI)

• use after 2 months postpartum

• After return to positive energy balance

• Temporarily induces negative energy balance (NEB) followed by compensation in feed intake

body tissues

uptake of glucose for energy

oxidation of amino acids for energy

liver

gluconeogenesis

adipose tissue

Uptake of glucose and acetate

Lipogenesis during positive energy balance

Lipolysis during negative energy balance

Glucose from glycerol via lipolysis

mammary gland

blood flow

milk synthesis

glucose uptake and lactose synthesis

NEFA utilization for milk fat synthesis

amino acid utilization for milk proteins

maintenance of secretory cell number

involution

- natural regression of the mammary gland after peak lactation

- after peak lactation, milk yield drops ~ 5%month

Mammary Changes with Involution

• Cellular metabolic activity slows

• Secretion rate/ cell declines

• Size & number of alveoli decline

• Number of cells/alveolus decline

• Proportion of connective tissue increases

• Mammary gland DNA content declines

Biochemical changes:

- decreased fatty acid, acetate, glucose incorporation into lipid

- reduced mitochondrial function

- reduced oxidation of glucose; reduced ATP

Acceleration of involution:

- cessation of suckling/ milk removal accelerates involution (dry period, mastitis treatment) and of milk removal increases alveolar pressure:

• accumulation of product

• disruption of microtubule transport

• disruption of alveolar walls (myoepithelial cells remain intact)

• increased SCC

Retarding Involution

• Routine oxytocin administration

• PRL, STH, T3, T4 retard involution

• Continued milking/suckling stimulus provides physical/endocrine stimulus and neurostimulation (milking/ suckling stimulus)

• increases PRL, ACTH

• frequent milk removal serves to keep mammary pressure low

Lack of a dry period reduces next lactation yield by

25-33%

Length of dry period: effects

- dry periods less than 40 days and more than 60 days result in decreased lactation yield

- dry periods longer than 45 days do not increase lactation yield

- short dry periods result in lack of complete epithelial cell regeneration

the mammary gland differs from other organs in that:

• 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)

Metabolic changes for mammary function

• Induces an increase in metabolic rate

• demands increased blood flow (400-500 unitsblood/unit milk)

• demands increased nutrient supply

• an inability to accommodate demands will result in metabolic disorder (milk fever(hypocalcemia), ketosis (hypoglycemia)

Functions of Mammary Cells

• substrate breakdown

• create energy

• synthesize enzymes: protein (caseins), lipid (milkfat), sugar, (lactose)

• Regulate transport of non-manufactured milk components

Differences in solute concentrations in milk vs. blood:

• sugar x 90 (90 x more sugar in milk vs.blood)

• fat x 9

• calcium x 13

• phosphorous x 10

• protein x 0.5

• sodium x 0.15

milk precursors made in rumen

propionate

acetate

butyrate

milk precursors made in small intestine

amino acids

glucose

components of glucose and where its made

propionate

amino acids

liver

Glucose Synthesis

• Propionate (C3) → liver gluconeogenesis → glucose(C6)

• Export to blood

• Storage as glycogen (glycogenesis)

Mammary cell glucose sparing:

• glucose used primarily for lactose synthesis

• very little glucose used for fatty acid synthesis

• fatty acid synthesis relies primarily on acetate

• very little glucose diverted to acetyl-CoA (Krebs cycle)

Mammary gland uses ________% of blood glucose available

60-85%

__________% of glucose taken up by cell is used for lactose synthesis

60-70%

lactose(12C) is a disaccharide comprising...

glucose 6C and galactose 6C

some glucose converted to __________

UDP galactose

Lactose synthetase =

galactosyl transferase + α-lactalbumin

how is glucose used in mammary cell?

60-70% goes to golgi aparatus for lactose synthesis and UDP galactose

20-30% goes pentose phosphate pathway for cofactors and precursers