Physiology of Lactation

________ stimulates prolactin secretion by the anterior pituitary by 10-20 fold. This is regulated by _______, which as an inhibitory effect.

(1) Estrogen (2) human placental lactogen (hPL)

_______ oral contraceptives can have detrimental effects on quantity and quality of breast milk, especially if started before breastfeeding is well established. On the other hand _______ contraceptive methods do not have any adverse effects on milk volume.

(1) Estrogen-containing (2) Progesterone only -NOTE: Combined oral contraception may be started from six weeks if breastfeeding is established and other contraceptive methods are unacceptable.

What are the pathways for milk secretion by the mammary epithelial cell?

(1) Exocytosis: milk protein and lactose are transported in Goli-derived secretory vesicles, with water and electrolytes into the alveolar lumen (2) Reverse Pinocytosis: lipid formed in smooth ER forms droplets and covered by phospholipid membrane transported as milk-fat globule (3) Apical transport: direct movement of monovalent ions, water, and glucose across the apical membrane of the cell. (4) Transcytosis: sodium, potassium, chlorides, some monosaccharides, and water (5) Paracellular pathway: some interstitial fluid components and leukocytes to pass by diapedesis through tight junctions.

______ results in a failure to lactate while _____ results in galactorrhea and decreased libido. It can also cause a failure to ovulate and amenorrhea.

(1) Prolactin deficiency (2) Prolactin excess

What are maternal problems that affect lactation?

-Stress -PCOS -Theca lutein cysts -Obesity -Labour analgesia -Type 1 DM -Placental retention -Alcohol dependence

What effect does lactation have ovulation?

As long as lactation continues, there is suppression of ovulation, because prolactin inhibits GnRH secretion by the hypothalamus and FSH and LH secretion by the anterior pituitary.

____ inhibits pituitary release of oxytocin (and ADH) and thus indirectly decreases myometrial contractility.

Ethanol

Prolactin secretion is tonically inhibited by ________.

dopamine (prolactin-inhibiting factor) -Thus, interruption of the hypothalamic-pituitary tract causes increased secretion of of prolactin and sustained lactation.

______ is the spontaneous flow of milk from the nipple at any other time other than nursing. This condition is often associated with the over production of ______ from a pituitary adenoma.

(1) Galactorrhea (2) prolactin NOTE: Ethanol can cause hyperprolactinemia by elevating prolactin release from lactotrophs by increasing the number of lactotrophs in the anterior pituitary gland.

What are the five stages of lactation?

(1) Mammogenesis- development of breast to a functional state (2) Lactogenesis- synthesis and secretion of milk from the breast alveoli (3) Galactokinesis- ejection of milk outside the breast (4) Galactopoiesis- maintenance of lactation (5) Involution- regression and atrophy post-lactation.

What besides inhibition of dopamine what other factors stimulate prolactin stimulation?

(1) Suckling- mediated by a decrease in the amount of dopamine released at the median eminence, reliving the lactotropes from tonic inhibition. (2) Estrogen- stimulates growth of the lactotropes during pregnancy as well as prolactin gene expression and release.

In early pregnancy a marked increase in ______, _______ & ____ is evoked by luteal and placental hormones.

(1) ductular sprouting, branching, and lobular formation.

When the _________ cycle is established, there is extensive branching of the duct system and parenchymal proliferation and canalization of the lobuloalveolar units controlled by ____ & ____.

(1) hypophyseal-ovarian-uterine (2) estrogen and progesterone

What can affect can infrequent suckling/failure to empty breast have?

Causes elevated intra-mammary pressure -Disrupts the connections between cells and their attachment to the basement membrane disrupting synthesis and secretion of milk components.

What are the variations in breast milk composition?

Colostrum (1-5 days)- is richer in proteins, minerals, immunoglobulins, anti-inflammatory factors, phagocytes and lymphocytes. Mature milk (>30 days)- larger quantity than colostrum Foremilk- thin, proteins, lactose, water, and other nutrients. Hindmilk- more fat therefore white provides much of the energy of a feed.

What hormones play a role in prepubertal growth of breast?

Depends on estrogen and progesterone. Secretion of prolactin and somatotropin by the pituitary gland results in mammary growth. -Adrenocroticotrophic hormone (ACTH) and TSH acting on the adrenal gland and thyroid gland also play a minor role in the growth of the mammary gland.

_______ depends on the suckling mechanism of the baby and the contractile action which express milk from the alveoli into ducts. This contraction is brought about by the action of oxytocin.

Galactokinesis -Inhibited by psychic condition/pain/breast engorgement.

______ is an enlargement or swelling of breast tissues in males. It is most commonly caused by male estrogen levels that are too high or are out of balance with testosterone levels.

Gynecomastia

_______ is apoptotic cell death and tissue remodeling post lactation. It requires a combination of lactogenic hormone deprivation and local signals to undergo regression and atrophy.

Involution

What are the actions of prolactin?

It is structurally homologous to growth hormone: (1) Is the major hormone responsible for lactogenesis. (2) Participates, with estrogen, in breast development (3) Inhibits ovulation by decreasing synthesis and release of GnRH (4) Inhibits spermatogenesis by decreasing GnRH.

_____ describes the production of breast milk and its secretion from the mammary gland after delivery.

Lactation

Prolactin levels steadily increase over the course of a pregnancy. Although the prolactin levels are high, how come lactation does not occur during pregnancy?

Lactation does not occur because estrogen and progesterone block the action of prolactin on the breast. -After parturition, when estrogen and progesterone levels fall precipitously their inhibitor effects on the breast are removed and lactation can proceed.

_______ is the growth of ducts and lobuloalveolar systems and this starts from birth to puberty and continues in pregnancy.

Mammogenesis -Ductal sprouting predominates in the 1st trimester and locular sprouting occurs more in the 2nd trimester.

_____ is released from the posterior lobe of the pituitary gland during nipple stimulation or sensory stimulation. It causes ejection of milk from the alveoli gland by contraction of the myoepithelial cells.

Oxytocin -ADH is usually released in conjunction with the release of oxytocin

What is the hormone for the maintenance of lactation?

Prolactin -Suckling is essential for the maintenance of milk secretion (Galactopoiesis)

Stage ____ of lactogenesis occurs in mid pregnancy. During this stage there is initiation of milk synthesis, the alveoli differentiates into secretory cells and prolactin stimulates mammary secretory cells to produce milk.

Stage 1 -Insulin and serum growth factor induce cell division of stem cells of the gland and presence of cortisol for the formation of alveoli is required for induction of milk synthesis. -Further differentiation is inhibited by high levels of progesterone from the placenta and loss of progesterone receptors in the lactating breast.

Stage ____ of lactogenesis occurs from late pregnancy to day 8. This is triggered by a rapid drop in progesterone levels after placental delivery. Requires the presence of elevated levels of prolactin and cortisol, insulin growth hormone, and parathyroid hormone to facilitate mobilization.

Stage 2 -There is a switch from endocrine to autocrine control.

What are the type of lobules?

Type 1- (virginal lobule) when an average of 11 alveolar buds/ductules cluster around a terminal duct, this is apparent within 1 to 2 years after onset of menses Type 2- changing levels of estrogen and progesterone during menstrual cycle stimulates type 1 lobules to sprout new alveolar buds and evolve to mature structures, type 2-47 lobules Type 3- in pregnancy, 80 lobules Type 4- attained in late pregnancy with breast milk