Mammary Gland Bio Function PDF

Royal College of Surgeons in Ireland – Medical University of Bahrain Mammary gland and lactation Module : Endocrine Class: MedYear1 semester 2 Date: 7 February 2024 Lecturer : Paul O’Farrell Learning objectives Identify the key hormones involved in milk synthesis and release...

Royal College of Surgeons in Ireland – Medical University of Bahrain Mammary gland and lactation Module : Endocrine Class: MedYear1 semester 2 Date: 7 February 2024 Lecturer : Paul O’Farrell Learning objectives Identify the key hormones involved in milk synthesis and release Outline the biosynthesis of lactose in the lactating mammary gland Compare and contrast the composition of human and bovine milk State the current WHO breast feeding recommendations for infants and outline the aim of the International Code of Marketing of Breast- milk Substitutes Why breast feed? Fits perfectly to baby's needs. Contains all needed nutrients, no need for supplemental vitamins*. Provides nutritional factors for optimal growth and development. Has immunity factors; reduced rates of infection Protects against allergies in baby. Assists with normal jaw, tooth and speech development. Always available. Always the right temperature. Always the right amount, even for triplets. Provides closeness: enhances bonding. Milder odor to baby's stools, compared to the artificially fed infant. Protects against colic. Increases maternal postpartum weight loss, compared to artificial feeding. Improves maternal health by increasing the level of maternal circulating antibodies. [in developing countries, lack of safe water for formula] Research ongoing ; microbiome; epigenetics; etc  Why formula feed? Feeling that breastfeeding is repulsive or lacks appeal A sense that breastfeeding is too embarrassing A busy lifestyle or feeling that breastfeeding will tie her down She feels that she is too nervous to breastfeed Breastfeeding seems too complicated or restrictive She is overly concerned that she can't measure the baby's intake Difficulty in getting baby to ‘latch on’ Specific medical issues eg special dietary requirements, reflux, failure of baby to put on weight … Other issues The Breast Mammary Gland : an exocrine gland Guyton & Hall 82.10 Breast development At birth, breast has lactiferous ducts but few (or no) alveoli At puberty, estrogens promote further growth of and branching of ducts and initiation of lobules Exposure to estrogens and progesterone as the menstrual cycle develops promotes additional growth and development of lobules and alveoli, breasts increase in size due to deposition of fat and growth of connective tissue (cyclical changes occur in the breast during menstrual cycle due to the fluctuations in hormone levels) The breast is not competent to produce milk until pregnancy During early pregnancy, estradiol and progesterone (insulin? prolactin? other growth factors?) lead to hypertophy of duct-lobule-alveolus – dilation of alveolar lumen Mid-pregnancy – duct and lobule growth is mostly finished, alveolar epithelial cells become competent to secrete milk Clinical note: pregnancy and breast cancer Final differentiation of certain breast tissue cells does not occur until the end of pregnancy The less-differentiated cells are at a higher risk of becoming cancerous - pregnancy protects against breast cancer Later primigravida offers less protection, (Prof Uwe) Hormonal control of milk production - Prolactin Prolactin: peptide hormone produced in anterior pituitary Promotes lactation Levels rise steadily during pregnancy to reach 10-20 times pre-pregnancy levels However, its actions are opposed by progesterone from placenta Loss of placenta at birth reduces progesterone levels and releases block on milk production Basal prolactin levels fall after birth, but suckling of baby sends nervous signals that promote its release Duration and intensity of stimulation is proportional to prolactin production and therefore milk production → Twins stimulate more milk production Hormonal control of milk production - Prolactin Johnson & Everrit “Essential Reproduction” 14.5 Hormonal control of milk production - Prolactin Hormonal control of milk ‘letdown’ - oxytocin Oxytocin is a nonapeptide hormone released from posterior pituitary Milk is made in alveoli but does not easily leave them – it must be ejected Suckling of baby sends nervous signal to hypothalmus resulting in synthesis and release of oxytocin Oxytocin travels in bloodstream to breast and causes the myoepithelial cells to contract, expelling milk from alveolus Sucking on one breast causes milk to flow in the other also Fondling baby, hearing baby cry – emotional response can also release oxytocin and cause milk to flow Hormonal control of milk ‘letdown’: oxytocin – the “Milk Ejection Reflex” Johnson & Everrit “Essential Reproduction” 14.6 Fertility is reduced during lactation Menstruation and ovulation return more slowly in lactating women (menstruation is a poor indicator of fertility: conception can occur without an intervening menstruation) Reduction in fertility probably mediated by prolactin which can suppress release of GnRH → no release of FSH and LH → no cycle UNRELIABLE as a method of contraception – (“Irish twins”) Hormones hormone source function prolactin anterior promotes synthesis of milk; pituitary induction of alpha- lactalbumin; oxytocin posterior milk ejection – ‘letdown’; pituitary “caring behavior” progesterone placenta breast development in pregnancy; opposes milk synthesis estrogens placenta breast development in pregnancy; opposes milk synthesis hGH, cortisol, various general breast development, parathyroid hormone, enlargement, general milk insulin production Milk composition ‘Curds’ ‘Whey’ proteins Fat provides ~50% of calorific value (in human) Protein is twice as much in bovine as in human Lactose is 50% greater in human “Ash” contains K, P, Ca and other minerals – 3 times as much in bovine Compositional changes Colostrum is produced in early lactation Yellowish (due to β–carotene), sticky, ~ 40 mL/day less fat, greater amounts of proteins, some minerals, fat- soluble vitamins Transitional phase Mature milk after 2-3 weeks Lower IgA, lactoferrin, cells ~400 mL/day Compositional changes Fore milk produced first in feeding session has lower fat content Hind milk produced later in feeding session, higher fat content – fat may help to induce satiation in infant Also, diurnal changes: maternal diet, maternal hormonal changes Synthesis of milk Milk components are synthesised by alveolar epithelial cells Johnson & Everrit “Essential Reproduction” 14.4 Lipids Lipids provide ~50% of the energy content of milk Triglyceride, fatty acids incl omega-3 and omega-6 FAs, cholesterol, phospholipids, fat-soluble vitamins.. Short and medium chain FA synthesised in breast From blood glucose and ketone bodies Longer chain FA from bloodstream Chylomicrons, VLDL, FFA Either from diet, adipose, or synthesised in other tissues (liver) Glycerol backbone for triglyceride made from blood glucose Milk fats made on ER Globules enlarge and press against membrane of alveolar epithelial cell bulging out, eventually membrane closes behind them and membrane-bound globule enters alveolus Proteins Lactalbumin, lactoferrin, immunoglobulins, albumin, enzymes (e.g., lysozyme), growth factors, hormones …. – formula generally has a higher casein/whey ratio (whey is easier to digest), higher overall protein content, denatured and inactive enzymes and immunoglobulins, more allergenic Amino acids from bloodstream Generally from diet Some from mobilization of muscle and liver proteins Proteins pass through Golgi and are exocytosed into lumen Casein: proteins with low solubility that complex with calcium Whey: proteins left in solution after clotting Milk synthesis - lactose Lactose –’milk sugar’ – a disaccharide Galactose with a β-1,4 linkage to glucose Synthesised from blood glucose Glucose is converted to galactose and activated by coupling with UTP to give UDP- Galactose UDP-Galactose is joined to another glucose by lactose synthase Lactose Lactose Synthase : two proteins: Protein A: β-D-galactosyltransferase - Enzyme - found in a number of body tissues where it is involved in making the sugar chains for glycoproteins – transfer of galactose is to N-acetyl-D- glucosamine to generate N-acetyllactosamine Protein B: lactalbumin - Found only in lactating mammary gland - Modifies substrate specificity of galactosyltransferase - Induced by prolactin Lactose formed within Golgi and passes to lumen of alveolus with protein exocytosis Lactose functions to: - Provide energy - Promote growth of Lactobacillus bifidus and thus colonisation of gut by ‘good’ bacteria - Promote absorption of minerals (esp. calcium) from milk Immunological properties Milk provides passive immunity and protects baby while its immune system is still developing Antibodies: mostly IgA; packaged with a secretory component that protects antibody from digestion Lactoferrin sequesters iron – making it unavailable to pathogenic bacteria Lysozyme attacks bacteria Lactose – promotes good bacteria, out-competes bad bacteria Leukocytes 104-105 macrophages per mL of milk (~90% of cells in mature milk) Infant formula Based on Cow’s milk, but further processed: Processing includes steps to: –alter the whey-to-casein protein balance to one closer to human milk –addition of several essential ingredients (fortification) –partial or total replacement of dairy fat with fats of vegetable or marine origin Nutritionally inferior to breast milk but superior to other substitutes, such as unprocessed milk from cows Untreated cow's milk is not recommended before the age of 12 months International code on marketing of breast-milk substitutes International health policy framework adopted by WHO member states in 2002. Only ~39% of children globally are exclusively breastfed for four months The Code seeks to: promote and protect breastfeeding control marketing practices used to sell products for artificial feeding give health workers the responsibility to encourage and protect breastfeeding WHO infant feeding recommendation “Breastfeeding is an unequalled way of providing ideal food for the healthy growth and development of infants; it is also an integral part of the reproductive process with important implications for the health of mothers. As a global public health recommendation, infants should be exclusively breastfed for the first six months of life to achieve optimal growth, development and health. Thereafter, to meet their evolving nutritional requirements, infants should receive nutritionally adequate and safe complementary foods while breastfeeding continues for up to two years of age or beyond. Exclusive breastfeeding from birth is possible except for a few medical conditions, and unrestricted exclusive breastfeeding results in ample milk production”. Worldwide average for exclusive breastfeeding in the first 6 months is 35% 12% Qatar, Kuwait 10% Bahrain 31% Oman; 13% USA 31% Saudi Arabia; 14% Ireland (2 months) Other points Some care must be taken with mothers with restricted diets – eg vegan Diabetic mothers need special care Variable demand for glucose for milk production Vitamin D – American academy of pediatrics recommends supplementing breastfed infants with 400 IU/day (2008) Vitamin K Babies have low reserves of vitamin K at birth Vit K is needed for clotting Vit K is low in some mothers’ breast milk (often due to drugs administered during pregnancy) Vit K is routinely administered prophylacticaly to newborns (haemolytic disease can be sudden and severe) Reading Guyton and Hall ch. 82 emedicine lactation https://www2.hse.ie/babies- children/breastfeeding/