96. Mammary gland development, lactogenesis Flashcards
Phases of mammary gland development
Mammogenesis • development of the gland Lactogenesis • milk synthesis, milk secretion Galactopoesis • maintenance of milk production Ejection • milk let down Involution • regressive transformation of the gland
Mammogenesis
Mammogenesis: development of the mammary gland • Mammary development begins when the animal is an early fetus and proceeds beyond initiation of lactation. • The mammary gland is one of a few tissues in mammals, which can repeatedly undergo growth, functional differentiation, and regression.
4 stages of mammogenesis:
- Development before birth 2. Development from birth to pregnancy 3. Development during pregnancy 4. Development during lactation
- Development before birth:
• influenced by endocrinological mechanisms during early embryonal phase. • Androgens (testosterone, etc.) inhibit the process in male fetuses, which will regulate normal mammogenesis in females around puberty. • (Administering androgens to females during early embryonic phase will lead to the lack of mammogenesis at puberty.)
2.Development after birth until first pregnancy:
Stages: 1.Isometric growth • mammary growth rate is similar to the body’s • Cow: during 2 - 3 months after birth • mostly fat pad and connective tissue growth. 2.Allometric growth • mammary growth rate is 3.5times higher than the body’s • Itbeginsjustpriortothefirstestruscycle.Lastsfor2-3 months following puberty (cow) • Mostlyductulargrowth. 3.Isometric growth • mammary growth rate is similar to the body’s • Cow:12-15months(untilconception) • furtherductulargrowth. 324
3..During the period of pregnancy:
Further lobulo-alveolar development happens also due to endocrinological effects • PRL, Glucocorticoids, Placenta lactogen • Local factors are also playing important role (IGF, EGF, etc.)
- During lactation:
Further alveo/lobular growth until peak lactation, then regression happens. Mammary epithelial cells begin to secrete During dry period: • Secretory cells go through on regression (involution), preparation for the next lactation phase. During Lactation • Continuous growth until peak-lactation. • Milk production is related to the number of secretory cells and secretory activity. • During lactation the number of dying cells is higher than the number of growing cells. • Mammary gland has more secretory cells at the beginning of lactation than at the end of lactation. -During dry period: • Secretory cells degenerate (involution) to prepare for the next lactation.
Hormonal effects in mammogenesis (GH, Glucocorticoids)
Growth hormone • Development of parenchyma, expression of epithel receptors. Glucocorticoids: • Important in the development of ducts + in the growth of lobulo-alveolar structure (jointly with GH,PRL, E2, P4)
Hormonal effects in mammogenesis (Estrogen,progesterone)
Estrogen: • significant species differences • Stimulate development of parenchyma (it is a must in cow; but not essential in sheep (ie: ovaryectomy (ovx) will not inhibit the development). IGF is also important, as a transmitter of effect. Progesterone: • Stimulating lobulo-alveolar development, especially during the later phase of pregnancy (beyond, it is the inhibitor of lactogenesis)
Hormonal effects in mammogenesis (Prolactin, placenta lactogen,lacal factors)
Prolactin (PRL): • species differences • It has permissive effect on steroids in cow,(an essential factor of mammogenesis in rodents) Placenta lactogen: • GH- and PRL-like effect, influence the size (body mass) of calf, as well as the would be milking capacity. Local factors: • i.e. IGF is absolutely necessary for E2 & GH in order to influence mammary gland development. • IGF generally stimulate cell growth, cell differentiation, maintains cell functions, prevents from apoptosis.
Lactogenesis
Initiation of lactation is a series of cellular changes whereby mammary epithelial cells are converted from a non-secretory state to a secretory state. This process is normally associated with the end of pregnancy and around the time of parturition. Two-stages • Stage I: Cytological and enzymatic differentiation of the epithelial cells. • Stage II: Intensive secretion of milk.
Lactogenesis; Stage I:
Cytological and enzymatic differentiation of alveolar epithelial cells • very limited milk synthesis and secretion just before parturition • specific milk components (e.g. fat droplets and proteins) make their first appearance in the mammary gland. • Formation of colostrum (and immunoglobulin uptake). P4 + E2 inhibit the real milk production in Phase I. The few drops of milk before parturition is also called pre-colostrum • Lactose synthesis does not begin until stage II of lactogenesis. Stage I of lactogenesis may thus be characterized as due to gradual chemical and morphological changes (such as closure of tight junctions), and
Lactogenesis; Stage II:
Copious secretion of all milk components • Stage 2 of lactogenesis is usually shorter than stage 1 In the cow this begins about 0-4 days before parturition and extends through a few days postpartum. • Copious milk secretion begins when the inhibitory effects of progesterone on lactogenesis decreases and the stimulation by the very high blood concentrations of prolactin and glucocorticoids (associated with parturition) occur. • Colostrum and then milk synthesis and secretion occur during Lactogenesis II stage II as the result of abrupt cardiovascular, metabolic and secretory changes
Hormonal effects in lactogenesis
Progesterone Prolaktin Glucocorticoids Estrogen PGF2alpha
Hormonal effects in lactogenesis Progesterone:
antilactogenic • Mechanism of inhibition of lactogenesis: Inhibits synthesis of α-lactalbumin and casein. Decreases the ability of prolactin to induce protein synthesis Competes with glucocorticoids for binding receptors Reduces synergism between prolactin and glucocorticoids.
Hormonal effects in lactogenesis Prolactin:
• Lactogenic • Both the availability and the responsiveness of PRL receptors in the mammary gland are important for lactogenesis. • PRL increases milk protein synthesis. • Controls expression of genes necessary for casein synthesis. • High PRL level is a must for all species in order to maintain the permanent milk production except the cow, where milk production can be maintained even if PRL decreases (GH takes over the role) 339
Hormonal effects in lactogenesis Glucocorticoids:
• lactogenic hormones. • They induce differentiation of rough endoplasmic reticulum and Golgi apparatus. • The differentiation is necessary for prolactin induced protein synthesis. • There is a synergy between prolactin and glucocorticoids for lactogenesis.
Hormonal effects in lactogenesis Estrogen:
Estrogen: • (Indirect) lactogenic hormone • Increases secretion of PRL and other lactogenic hormones from the pituitary gland. • Increases the number of PRL-Receptors in the mammary cells. • Stimulates synthesis of casein and alfa- lactalbumin.
Hormonal effects in lactogenesis Local factors in lactogenesis • PGF2α
produced by uterus and mammary gland. Inhibits the milk secretion, therefore it has to be inactivated/or eliminated at parturition. PGF2a is further reduced during suckling. In case the number of newborns are lower than the active glands, then the inactive glands are going through on regression due to the inhibitory effect of PGF2a. Suckling, on the other hand, further stimulates the secretion of lactogenic hormones.
Lactose in lactogenesis
Decreasing P4 and increasing glucocortiociods and PRL secretions initiate the synthesis of α-lactalbumin. • α-lactalbumin interacts with galactosyltransferase in the Golgi apparatus in synthesis of lactose. Synthesis of lactose osmotically draws water into the Golgi and secretory vesicles. This process allows for secretion of large amounts of milk and is the most obvious manifestation of stage 2 of lactogenesis. At the same time, synthesis of other milk components is increased. (The content of α- lactalbumin in the mammary tissue is an indicator of lactogenesis).
Role of colostrum
Colostrum (and precolostrum) is produced in lactogenesis phase Role: • Maternal immunity • Nutrient role • Laxative effect
- Maternal Immunity
The colostrum is produced during lactogenesis stage 2 It has several functions: • Immunoglobulins are transmitted from the maternal body into the fetus (passive immunity). Several antigens (bacteria, viruses and other pathogens) are specific to a certain herd. The newborn has to be raised in the same environment where the mother was exposed to these antigen stimulations (this way it can be avoided that the infant meets such pathogens against which it is not have immune globulins). There are two ways of getting immunoglobulins into the fetus: • Transplacental transport: dependent on the number of placenta layers, so it is typical of primates and rodents. • Absorptionthroughthedigestivetract.
- Nutrient Role:
• Compared to the milk, colostrum contains more protein, lipids and minerals; and less lactose (except in mare). • Water, fat soluble vitamins (mainly vitamin A, the transport of which through the placenta is limited) and essential amino acids are also present in a significant amount.
- The laxative effect
is caused by the mucus-like components, which cover the wall of the intestines and help the passage of nutrients. Mucous components in the colostrum also help to remove the meconium (embryonal faeces).
