2. Lactation Physiology (part 2) By: A. Riasi (PhD in Animal Nutrition & Physiology) فیزیولوژی تولید و ترشح شیر

3.  At the end of this section students will be able to reply  How is the blood flow of mammary gland?  What is the importance of the udder lymphatic network?  What is the neuroendocrine reflex of milk ejection?  How is Immunoglobulin transport in the mammary gland?  What is galactopoeisis?  How change the mammary gland physiology during the dry period?  What are the allometric and isometric growth of mammary gland?  What is the role of hormones in mammogenesis?

4.  Mammary blood supply  Milk synthesis rate depend to the rate of blood flow of udder.  Blood flow in the mammary gland increase before parturition.  The efficiency of extraction of the components from the blood while it passes through the udder is more important.

5.  Mammary blood supply

6.  Mammary lymphatic network

7.  Mammary nervous system  The efferent innervation of the mammary gland is entirely sympathetic in origin.  Innervation of the udder is sparse compared with other tissues.  Sensory nerves are involved in milk ejection and found in the teats and skins.  There is no parasympathetic innervation to the gland.  Sympathetic nerves are associated with the arteries but not with alveoli.  There is no innervation of the secretory system.  Few nerves go to the interior of the udder.

8.  Milk ejection  Oxytocin has the main role in milk ejection and causes contraction of the myoepithelial cells.  The time from the start of a tactile stimulation until the occurrence of milk ejection is different.  Milk ejection reflex actually is a neuroendocrine reflex.  The reflex has two pathways:  Afferent Pathway (neural)  Efferent Pathway (hormonal, blood-borne)

9.  Milk ejection  Other mechanisms of milk ejection:  Myoepithelial cells will also contract in response to vasopressin (ADH or antidiuretic hormone).  Milk ejection may be a condition response.  Stimulation of the genital tract such as vaginal distention causes release of large amounts of oxytocin.  The mechanical tap stimulus does not involve oxytocin.

10.  Effect of stress on milk ejection  Various stressful stimuli that inhibit milk ejection are associated with increased activity of the sympathetic nervous system.  Role of autonomic nervous system  Sympathetic nerves, The neuroendocrine components of sympathetic nerves are:  Epinephrine  Norepinephrine

11.  Colostrum production  Colostrum has larger amounts of specific proteins than milk:  Immunoglobulins  Antimicrobial peptides (lactoferrin and lactoperoxidase)  Other bioactive molecules, including growth factors  Under certain circumstances, the maternal antibodies may attack and destroy the newborns red blood cells (neonatal isoerythrolysis).

12.  Immunoglobulin transport in the mammary gland  The IgGs make up the majority of immunoglobulin in cow colostrum.  Most of the IgA and IgM that are transported into colostrum are synthesized by the plasma cells (B lymphocytes).  Transport of the immunoglobulins occurs through the epithelial cells by a process involving small transport vesicles.

13.  Bioactive factors in colostrums and milk  Colostrum and milk contain many factors that can influence cell growth, differentiation, and function:  Glutamine  Polyamines  Nucleotides

14.  Galactopoeisis  Galactopoeisis is the maintenance of lactation once lactation has been established.  Two key interrelated components for maintenance of lactation:  Galactopoietic hormones  Prolactin  Growth hormone  Removal of accumulated milk

15.  Galactopoeisis  Role of local mammary factors in regulating milk secretion.  Feedback inhibitor of lactation (FIL) found in milk.  FIL is thought to be produced by the mammary cells as they synthesize and secrete milk.

16.  Physiology of mammary gland during the dry period  During dry period the gland has three distinct functional states:  The period of active involution  The period of steady state involution  The period of lactogenesis and colostrogenesis:  Regeneration and differentiation of secretory epithelial cells  Selective transport and accumulation of immunoglobulin  The onset of copious secretion

17.  Physiology of mammary gland during the dry period  The mammary gland undergoing transition at two stages:  At the beginning of the dry period  At the end of the dry period

18.  Physiology of mammary gland during the dry period  Reducing the length of the dry period of dairy cows may affect:  Postpartum health  Reproduction performance  Milk production

19.  Physiology of mammary gland during the dry period  Intra-alveolar pressure triggers the events of active involution:  The appearance of lysosomes in the secretory epithelial cells.  M acrophages enter the mammary tissue and secretion.  The rate of synthesis of major milk constituents decrease:  Fat  Casein  Lactose *  Citrate *  β-lactoglobulin  α-lactalbumin

20.  Physiology of mammary gland during the dry period  By 7 days involution, the concentration of serum proteins in mammary secretion is significantly elevated.  The permeability barriers are not totally destroyed and the mammary gland maintains a degree of control.

21.  Physiology of mammary gland during the dry period  The concentration of the iron biding protein lactoferrin (Lf) dramatically increase.  The major site of synthesis of the Lf found in bovine mammary secretions is thought to be the secretory epithelial cell.  Lf is a major protein in the secretion of the non-lactating mammary gland.  Lactoferrin is bacteriostatic by virtue of its ability to bind iron with great affinity.

22.  Development of the Mammary Gland (Mammogenesis)  Mammary gland has allometric and isometric growth  The development of mammary growth has five phases:  Fetal phase  Prepubertal phase  Postpubertal phase  Pregnancy  Lactation

23.  Development of the Mammary Gland (Mammogenesis) Timeline for the development of the mammary gland in bovines Day 30, condensing ectodermal cells Day 35, mammary line Day 43, mammary bud Day 65, teat development Day 80, sprout Day 150, channel formation

24.  Development of the Mammary Gland (Mammogenesis)

25.  Prepubertal mammary growth begins as isometric growth, and before puberty becomes allometric.  A large portion of mammary growth before puberty is an increase in:  Connective tissue  Ductal growth  Growth of the fat pad

26.  Development of the Mammary Gland (Mammogenesis)  Feed restricted heifers have >30% larger mammary glands at puberty.  Feeding high energy diets during the prepubertal period suppresses serum bovine somatotropin (bST) levels.

27.  Development of the Mammary Gland (Mammogenesis)  Through the first several estrous cycles after puberty, rapid mammary growth continues.  Most of the growth is lost through regression during the luteal phase of each estrous cycle.  Nutrition plays an important, though controversial, role in postpubertal mammary development.

28.  Development of the Mammary Gland (Mammogenesis)  Mammary growth is a continuous, exponential process from conception to parturition  The greatest increase occurs in mass of parenchymal tissue in late pregnancy.  The increasing udder size during the fifth and sixth months of pregnancy is due to:  The elongation of mammary ducts  The formation of alveoli  The reduction of identifiable fat cells in the fat pad

29.  Development of the Mammary Gland (Mammogenesis)  Mammary growth continues in early lactation.  Persistency of lactation (maintaining peak milk yield) depends on the continual survival of those milk-secreting cells.  In rats, increases in total mammary DNA was seen from parturition until weaning.

30.  Hormonal control of mammogenesis  The ovarian steroids are important for mammogenesis.  The ovarian activity appears to mediate the actions of GH, specifically through changes in IGF-I.  During cyclic activity, there is no significant exposure to estrogens and progesterone together.  This takes place during late pregnancy when the CL produces large amounts of progesterone and the feto-placental unit generates elevated levels of estrogens.

31.  Hormonal control of mammogenesis  In vitro studies showed that estrogen plus prolactin and growth hormone stimulated mammary growth.  Subsequently, estrogen was observed to induce secretion of growth factors from pituitary, kidney, and mammary tumor cells.  Thus, it was postulated that growth factors secreted from extramammary tissues into serum may act via an endocrine mechanism to mediate the mammogenic effects of estrogen.

32.  Hormonal control of mammogenesis  Growth factors secreted locally from mammary tissue may mediate, via a paracrine or autocrine mechanism, estrogen effects on mammogenesis.  Prolactin was discovered to be critically important for initiation of lactation in the periparturient period in several species, including cattle.  Indeed in cattle, lactogenesis is the only function of prolactin clearly established to this day.

33.  Hormonal control of mammogenesis  Mammogenesis depends not only on hormonal concentration but also on:  Receptor availability within the mammary tissue  The presence of transport proteins and intracellular lipids that are capable of making steroids unavailable to the tissues.

34.  Hormonal control of mammogenesis  Several other hormones play a permissive and supportive role in mammary growth:  Placental lactogens  Adrenal gland hormones  Thyroid hormones  Relaxin  Parathyroid hormone  Effect of parathyroid hormone-related protein (PTHrP)

35.  Hormonal control of mammogenesis  Other factors that may affect mammogensis:  Insulin-like growth factors (IGF)  E pidermal cell factors (ECF)  Transforming growth factors (TGF)  Fibroblast growth factors (FGFs)