1. 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).

2. Definitions 1-Lactation : Formation or secretion of the milk 2-Lactogenesis : Change of mammary epithelial cells from non secretory state to secretory state 3-Galactopoiesis : Maintenance of milk production

5. Where does milk come from?
Milk produced in mammary epithelium within lobules
With nursing, oxytocin triggers contraction of myoepithelial cells and transfer to sinuses

7. Structures of the Mammary Gland
. 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

8. 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

9. Ductal System: Alveolar Tubule Secondary tubule Mammary duct
Ampula (lactiferous sinus)
Lactiferous duct

10. Fig

11. Stages of lactogenesis
Mamogenesis and Lactogenesis Galctopoesis

12. Breast development (mamogenesis)
During puberty
Estrogen stimulate proliferation of ducts and deposition of fat
Progesterone stimulate development of lobules

13. Breast development (mamogenesis)
During pregnancy
Complete development of glandular tissue

14. 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

15. 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

16. 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

17. Lactogenesis
Lactogenesis: cellular changes by which mammary epithelial cells are converted from a non secretory state to a secretory state:
Hormones involved:
Progesterone (suppresses milk secretion)
Prolactin and/or placental lactogen
Growth hormone
Glucocorticoids (Cortisol)

18. 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)

20. Stages of lactogenesis
Mamogenesis and Lactogenesis Galctopoesis

21. 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)

22. 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

23. 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

25. Suckling reflex

26. 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).

27. Hormonal Requirements for Secretory Activation
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.

28. Milk production is a
"use it or lose it" process. The more often and effectively the baby nurses, the more milk will be produced
Milk production <100 ml/day in day 1 postpartum
Milk production by day 3 reaches 500 ml/day

29. Suckling reflexes Mechanosensors in nipple Suckling Hypothalamus +
Nerve pathway
Increase prolactin-releasing factor
Decrease prolactin-inhibitory hormone
Posterior pituitary
Anterior pituitary
Increase oxytocin
Increase prolactin
Contraction
Myoepithelial cells
Increase milk ejection
Increase milk secretion

30. 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