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Copyright © 2011 by Saunders, an imprint of Elsevier Inc. LACTATION

LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

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Page 1: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

LACTATION

Page 2: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Objectives

• Hormonal requirement for breast development (Mamogenesis)

• Hormones involved in the process of lactation (Lactogenesis) and their physiological action

• Physiological basis of suckling reflex and its role in lactation

• Galactopoeisis

• Involution (the termination of milk production).

Page 3: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

STAGES OF LACTATION

1.Mammogenesis : Breast development from birth until during pregnancy. Prolactin,Estrogen, progesterone, placenta lactogen, and adrenocorticotropic hormone2.Lactogenesis : Creation of milk (hormones Pl.insulin, cortisol and throxine) Stage 1. Between midterm and 2days after birth.Stage 2. Between 2days and 8days postpartum .

Page 4: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

3. Galactopoiesis : Production and

maintenance of milk, from 9days until

wean.(PL, Thyroxine, Insulin, cortisol, Insulin

like growthg factors)

4. Involution : When breast stop making milk

entirely after weaning

Page 5: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Definitions

1-Lactation : Formation and secretion of the milk2-Lactogenesis : Change of mammary epithelial cells from non secretory state to secretory state3-Galactopoiesis : Maintenance of milk production

Page 6: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Page 7: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Page 8: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Where does milk come from?

Page 9: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Page 10: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

. Each breast consists of 12~20 lobes of secretory

tissue

a. Each lobe has one lactiferous duct

b. Lobes (and ducts) arranged radialy

c. Lobes composed of lobules

d. Lobules comprise alveoli

Structures of the Mammary Gland

Page 11: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Alveolar Structure:

• Alveolus - microscopic unit made up of alveolar cells with an open lumen for collection of secreted milk

• Alveolar cell (epithelial cell)- basic cell producing milk in the mammary gland

• Myoepithelial cell- muscle-like cell surrounding the alveolus; contracts to express milk from the alveolar lumen

Page 12: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Ductal System:

• Alveolar Tubule

• Secondary tubule

• Mammary duct

• Ampula (lactiferous sinus)

• Lactiferous duct

Page 13: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Fig. 20.53

Page 14: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Stages of lactogenesis

Mamogenesis and Lactogenesis Galctopoesis

Page 15: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Breast development (mamogenesis)

• During puberty

– Estrogen stimulate proliferation of ducts and deposition of fat

– Progesterone stimulate development of lobules

Page 16: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Breast development (mamogenesis)

• During pregnancy

– Complete development of glandular tissue

Page 17: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Breast development (mamogenesis)

• Endocrine system plays a major role in synchronizing development (mamogenesis) and function (lactogenesis) of mammary gland with reproduction

• Three categories of hormones:– Reproductive hormones (endocrine)

• Estrogen, progesterone, prolactin, oxytocin and hPL

– Metabolic hormones (endocrine)• GH, corticosteroids, thyroxin, PTH and insulin

– Mammary hormones (autocrine)• leptin

Page 18: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Breast development (mamogenesis)

• Reproductive hormones (direct effect)– Estrogen (placenta)

• Growth & branching of ductal system (with GH)

• Fat deposition in the stroma

– Progesterone (placenta) • Growth of lobule-alveolar system(budding of

alveoli and secretory changes in epithelial cells )

• Although estrogen and progesterone are essential for physical development of the breasts, they inhibit actual secretion of milk

Page 19: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Breast development (mamogenesis)

• Prolactin (anterior pituitary)

– Its level increases during pregnancy (10-20 times)

– Its main function is milk production

– Sudden drop in E & P after delivery allows milk production

– It is controlled mainly by hypothalamic hormone

• PIH (Dopamine)

• Human placental lactogen HPL(placenta)

– Facilitate mammogenesis

– Delays milk production

Page 20: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Lactogenesis

• Lactogenesis: cellular changes by which mammary epithelial cells are converted from a non secretory state to a secretory state:

– Hormones involved:

1. Progesterone (suppresses milk secretion)

2. Prolactin and/or placental lactogen

3. Growth hormone

4. Glucocorticoids (Cortisol)

Page 21: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Lactogenesis

• Lactogenesis :

– Suckling stimulates milk secretion with expansion of alveolar epithelium

– Lactation is maintained by emptying of milk

– 2 hormones involved

• Prolactin (milk production)

• Oxytocin (milk let-down)

Page 22: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Page 23: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Hormonal regulation of lactogenesis

• Metabolic hormones (direct effect)– GH

• Can be produced locally

• Its secretion is stimulated by progesterone

• Increases production of IGF-1 (insulin like growth factor) by the liver

– Corticosteroids • Increases during pregnancy (fivefold)

• Involved in breast development (permissive action on milk protein synthesis)

Page 24: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Hormonal regulation of lactogenesis

• Thyroxin

– Essential for milk production

– Thyroxin & TSH level decreases during lactation

• Insulin

– Low during lactation

– Shunt of nutrients from storage depots to milk synthesis

Page 25: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Galactopoeisis

• Definition: Galactopoeisis is defined as the maintenance of lactation once lactation has been established.

• Role of Hormones – Prolactin: Milk production – Growth Hormone: support increase in synthesis of lactose,

protein, and fat in the mammary gland– Glucocorticoids: galactopoeitic in physiological doses– Thyroid Hormones: galactopoeitic– Ovarian Hormones :

• Estrogen in very low doses is galactopoietic• Progesterone alone has no effect on galactopoeisis because there

are no progesterone receptors in the mammary gland during lactation

Page 26: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Page 27: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Suckling reflex

Page 28: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

The most critical time in the establishment of lactation is its onset, during the transition from pregnancy to lactation, a period now called secretory activation (previously termed lactogenesis stage II).

Page 29: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

The major inhibitor of milk production during pregnancy is progesterone.

Once birth occurs, a developed mammary epithelium, the continuing presence of high levels of prolactin, and a fall in progesterone are necessary for the onset of copious milk secretion.

Hormonal Requirements for Secretory Activation

Page 30: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Milk production is a

"use it or lose it" process.

The more often and effectively the baby

nurses, the more milk will be producedMilk production <100 ml/day in day 1 postpartumMilk production by day 3 reaches 500 ml/day

Page 31: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Suckling reflexes

Mechanosensors in nipple

Suckling

Hypothalamus

+

+

Nerve pathwayIncrease prolactin-releasing factor

Decrease prolactin-inhibitory hormone

Posterior pituitary Anterior pituitary

Increase oxytocin

Increase prolactin

Contraction

Myoepithelial cells

Increase milk ejection Increase milk secretion

+ +

+

+

Page 32: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Milk “Letdown”:

• Milk letdown is the evacuation of milk from the alveolar lumen to the duct system

– Nerves receive stimuli at the end of nipple

– Stimuli is received in the posterior pituitary

– Oxytocin is released from pituitary into blood

– Blood circulation brings oxytocin to mammary tissue

– Targets are the myoepithelial cells that contract

Page 33: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Page 34: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Page 35: LACTATION - كلية الطب€¦ · development (Mamogenesis) •Hormones involved in the process of lactation (Lactogenesis) and their physiological action •Physiological basis

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

1.Antibodies and other anti- infection agents are secreted in the milk2.Neutrophil and macrophages cells also secreted3.Particularly antibodies and macrophages that destroy ESCHERICHIA COLI (E COLI) bacteria which can cause lethal diarrhea in newborns