Hormones and Mammary Growth

TGF-b Effect on Mammary Growth in Culture

Epidermal Growth Factor and Mammary Growth

Major Endocrine OrgansBrain Hypothalamus

Pituitary Anterior Posterior

Thyroid

Parathyroid

Pancreas Islets of Langerhans

AdrenalCortex Medulla

Kidney

OvaryCorpus LuteumFollicle

Placenta

Hypothalamic-Pituitary Portal System

Hypothalamic-Pituitary Axis

Hypothalamus

AnteriorPituitary

CRF

ACTHGluc

ocor

ticoid

s

AdiposeLipolysis

LiverGluconeogenesisInhibit Insulin Action

MuscleProtein Breakdown

MammaryLactogenesisLactation

AdrenalCortexMedulla

Kidney

Hypothalamus

AnteriorPituitary

TRH

TSH

Thyroxin

IncreasedBasalMetabolicRate

Thyroid

Cold

Temperature Regulation

Hypothalamus

AnteriorPituitary

GnRH

FSH

FolliclesGrowth

Follicular Development

Mammary GlandDuct GrowthIncreased Progesterone Receptor

BrainSexual Behavior

UterusGrowth

Estroge

n

Hypothalamus

AnteriorPituitary

GnRH

LH

FollicleOvuation

Ovulation

Mammary GlandAlveolar Growthtogether with estrogen

Estrogen + Progesterone

Corp

us lu

teum

fo

rmati

on

Corpus luteum

Estrogen

BrainSexual Behavior

UterusMaintains Pregnancy

Estro

gen +

Proge

stero

ne

Estrogen + Progesterone

Hypothalamus

AnteriorPituitary

GHRH SomatostatinInhibits GH

AdiposeLipolysisInhibit insulin action

MuscleProtein synthesis or Breakdown Inhibits insulin action

MammaryIncreased Nutrient uptakeIncreased blood flow.

LiverGluconeogenesisInhibit Insulin Action

Body Growth

Hypothalamus

AnteriorPituitary

TRF DopamineInhibits Prl

MammaryLactogenesis,Lactation (some Species)

CL of Most RodentsCL formationProgesterone production(LH still induces ovulation)

Intestine

Pancreas

Islets ofLangerhans

CellsGlucagon

Opposite of insulin in liver and muscle

bCells

Produce Insulin

AdiposeGlucose uptakeFat synthesis

LiverGlucose uptakeGlycogen synthesisInhibits gluconeogenesis

MuscleGlucose uptakeGlycogen synthesisAmino acid uptakeProtein synthesis

MammaryLittle effectIncreases glucose uptakeAmino acid uptake

Insulin

Brain ?Food Intake

MammaryGrowth

Various OrgansNutrient Partitioning ?Cotyledon

Fetal Placenta Produces Placental Lactogen

Caruncle

Maternal Side of Placenta

Uterus

PlacentalLactogen

21181512963000

2

4

6

8

10

12

Estrogen

Progesterone

Estrous Cycle of Cow

Day of Cycle

Hormonal Levels Estrus Cycle-Parturition

Ovary on Growth

Control OvX Ovx + E0.0

0.5

1.0

1.5

2.0

2.5End Bud AreaDuct Length

Peripuberal Mammary GrowthWeeks 3-6 in Mice

Area

(mm

Sq)

or L

engt

h (m

m)

Estrogen ActionsEndocrine

Epithelium

Cell Division

Estrogen

Estrogen ActionsParacrine

Stroma

Cell Division

Growth Factors

Estrogen

Estrogen ActionsAutocrine

Cell Division

Growth Factors

Estrogen

Estrogen Signaling

Estrogen Receptor Localization in Mammary Ducts

Steroid Hormones and Mammary Growth in Heifers

2502001501005000

10

20

30

Estrogen

Progesterone

Prolactin

Placental Lactogen

Hormone Changes During Pregnancy in Cows

Days Pregnant

Estr

ogen

(pg/

ml)

Prog

este

rone

, Pro

lacti

n, P

lace

ntl L

acto

gen

(ng/

ml)

Control E P E+P0.0

0.2

0.4

0.6

0.8

1.0

1.2

E+P on Mammary GrowthPostpuberal Mice

Epith

elia

l Vol

ume

(mm

Cu)

Additive Response

Synergy

Estrogen and Progesterone Actions

Epithelium

CellDivision

Estrogen increases progesterone receptorIncreases growth

ProgesteroneIncreases growthAlveolar formation

Autocrine and paracrine actions are similar to estrogen alone.

0 5 250

2

4

6

8

10

- E+P+ E+P

Placental Lactogen on Mammary Growth

Bovine Placental Lactogen (µg/day)

% L

abel

ed E

pith

elia

l Cel

ls

Prolactin and Growth Hormone• Variable among species– Mice

• Pituitary required for growth• Which hormone depends on strain

– Cows• Little effect of prolactin on growth• Maybe some of growth hormone

– May be indirect

• At least some effects indirect– Somatomedin (IGF-I) from liver– Nutrient partitioning

Prl and GH Action

Receptor

Hormone

ActivationDimerization

PO4

ATP

ADP

Kinase Activation

JAK2

PO4STAT

NuclearTranslocationof STAT

Transcription

Estradiol and IGF-I Effect on Mammary Growth

Hormone Levels During Late Pregnancy

Hormone Levels Around Parturition

Hormone Levels at Calving