Lecture 7 Flashcards
Synthesis of arachidonic acid: direct pathway
Agonist binds to G-protein coupled receptor -> PLA2 -> arachidonic acid is released from membrane phospholipid.
Synthesis of arachidonic acid: indirect pathway
Agonist binds to G-protein coupled receptor -> PLC cascade.
DAG lipase releases arachidonic acid from DAG.
IP3 -> Ca2+ -> PLA2 (direct pathway).
MAPK also activates PLA2.
NSAIDs and childbirth:
NSAIDs block COX, so pregnant lady will be unable to enter labour.
20-HETE:
Most powerful vasoconstrictor in the body.
EET:
A powerful vasodilator.
Why is the uterus quiescent for most of pregnancy?
Shushed by progesterone and relaxin.
Initiation of labour: in rabbits
Withdrawal of placental progesterone evacuates the uterus.
Administering progesterone delays labour.
Initiation of labour: in humans
Different from rabbits, but progesterone is definitely involved in gestation length.
Stages of labour:
Stage 0: uterus is sleeping.
Stage 1: uterine awakening, initiation of parturition, complete cervical dilation.
Stage 2: activate labour, dilation to delivery.
Stage 3: delivery to expulsion of placenta, final uterine contraction.
Physiological changes during labour:
In stage 1: increased number of gap junctions between myometrial cells, increased number of oxytocin receptors.
Uterine contraction hormones:
Prostaglandins cause uterine smooth muscle contraction. Also cause softening, dilation, and thinning of cervix in early labour.
Oxytocin stimulates decidual cells to make more cells that produce prostaglandins.
Both (and estradiol) increase the number of gap junctions between uterine smooth muscle cells for synchronizing contractions.
Inducing labour:
Administer prostaglandin. Doesn’t care about stage of gestation or route of administration.
Oxytocin’s family:
Closely related to vasopressin. Probably evolved from vasotocin, the only neurohypophyseal hormone in nonmammalian nonvertebrates.
Oxytocin’s involvement in uterine contraction:
PLC cascade.
Ca2+ -> calmodulin -> myosin light-chain kinase.
Myosin light-chain kinase phosphorylates regulatory light chain and contraction begins.
Uterine sensitivity to oxytocin:
Insensitive until 20 weeks. Estrogen increases number of oxytocin receptors.
Oxytocin timeline in labour:
Fetal OT initiates labour.
Maternal OT maintains labour.
OT is released in bursts in stage 1 of labour.
Ferguson reflex:
Distention of cervix causes release of maternal OT.
Synergistic role of OT in labour:
In second stage, OT stimulates prostaglandin release.
Agents involved in sustaining labour: relaxin
Produced by corpus luteum, placenta, decidua.
Shushes uterus. Production increases during labour to soften cervix.
Agents involved in sustaining labour: mechanical factors
Stretch stimulates contractions.
Agents involved in sustaining labour: positive feedback
Contractions stimulate prostaglandin to increase intensity of contractions.
Stretch stimulates OT by Ferguson reflex. OT stimulates contractions.
Breast development at puberty depends on:
Progesterone and estrogens.
Full development of breasts at pregnancy requires:
Gradual increases in PRL, hPL.
High levels of estrogens and progesterone.
Kinds of hormones affecting breasts:
Mammogenic: proliferation of alveolar and duct cells.
Lactogenic: initiation of milk production.
Galactopoietic: maintaining milk production.
Galactokinetic: milk ejection.
Pathways for secreting milk components: secretory
Proteins synthesized in nucleus and sent out in vesicles.
Pathways for secreting milk components: transcellular endo/exocytosis
Proteins synthesized in nearby cells and sent out in vesicles.
Pathways for secreting milk components: lipid pathway
Lipids from nucleus travel freely through cell, then get exocytosed.
Pathways for secreting milk components: transcellular salt/water transport
Through cells using channels and transporters.
Pathways for secreting milk components: paracellular ion/water transport
Between cells.
Composition of milk:
Milk is an emulsion of fats in aqueous solution. Sugar: lactose Proteins: lactalbumin and casein Cations: K, Ca, Na Anions: Cl, phosphate
Mammogenic hormones: list
Estrogen, IGF-1, cortisol, prolactin, relaxin
Lactogenic hormones: list
Prolactin, hPL, cortisol, IGF-1, thyroid hormones, withdrawal of estrogens and progesterone.
Galactokinetic hormones: list
OT, slightly vasopressin
Galactopoietic hormones: list
Prolactin, slightly cortisol and other metabolic hormones.
Suckling response:
Sensory afferents synapse in SC.
Arcuate nucleus of hypothalamus disinhibits PRL by inhibiting dopamine.
In supraoptic and paraventricular nuclei of hypothalamus, afferent input triggers OT in post pit.
In preoptic area and arcuate nucleus, afferent input inhibits GnRH, leading to inhibition of FSH/LH.
