Reproduction 5 Flashcards
What type of cell secrets HcG?
What does this hormone bind?
What type of cells may it stimulate?
Syncytiotrophoblasts
First hormone secreted is hCG – human chorinic gonadotropin.
hCG binds to LH receptors on corpus luteum and keeps it viable
hCG is what pregnancy tests detect in urine
hCG also stimulates fetal Leydig cells and fetal adrenal cortex
Negative feedback actions on maternal HPG axis
What is thought to maybe be related to “morning sickness”?
Rapid rise in HCG is responsible for nausea “morning sickness”
When will hCG fall off? What does this indicate?
high levels of P prod. by CL critical. HCG keeps CL alive. peaks early on and eventually placenta becomes big enough that it can make its own steroid hormones… own P, own E… so HCG will then fall off
What secretes HPL? (What else is it referred to as?)
What does this hormone do? (What hormones does it act in a similar manner to?)
Describe these functions.
Syncytiotrophoblasts
Also produce human placental lactogen (hPL) (also called hCS – human chorionic somatommaotropin)
Similar to GH and prolactin
GH-like:
Counter-regulatory to insulin (anabolic and lipolytic)
Mobilizes glucose for fetal use
Stimulates fetal IGF-I
Prolactin-like:
Stimulates mammary gland development
Describe why pregnancy is an insulin resistant state. When is it insulin resistant?
second half of preg. rep very insulin resistant state
first half of preg. is v anabolic for mother- able to store a lot of nutrients… second half is accelerated starvation (developing fetus trying to suck up all nutrients and glucose away from mom) so fetus can grow. puts mom in state of metabolic starvation
mother prod. lots of prolactin from expanding lactotrophs in pit. gland. (stimulated by estradiol) … making lots of prolactin and that will act like GH and have anti-insulin actions (cause maternal glucose not to be taken up, then shunted over to fetus) potentiated by actions of HPL from placenta
Describe
GESTATIONAL DIABETES
Incidence?
What is it caused by?
Incidence – 3 - 8% (up to 16% in Native Americans)
Usually resolves with end of pregnancy, but up to 50% will go on to develop T2DM.
Caused by anti-insulin effects of hPL, progesterone, prolactin, and cortisol
preg. is physical stressor for body. cortisol levels high - catecholamines are high.
Describe the 3 main functions of the placenta.
What organs does it perform the role of?
Supportive – provides nutrients for fetal growth
Immune – prevents rejection of fetus by mother
Endocrine – synthesizes hormones
Performs the functions of: Gut- supplies nutrients Lung- gas exchange Kidney- regulating fluid volume and waste disposal Endocrine gland
cytotrophoblasts completely protected from maternal blood (so v protected, helps w this immune response)
How does placenta get cholesterol?
What enzymes does the placenta have/What can it synthesis?
placenta can’t make cholesterol HAS to get it from mother. usually in form of LDL
then can convert to P but thats as far as can go. does not have CYP17 and can’t make anything beyond progesterone by self. so progesterone shunted over to fetus and in fetal adrenal gland (prod. mostly androgens) …androgens can be sent back to mom which can convert these androgens to estradiol and estriol (E3) maintained in high quant. by placenta…
Which has a CYP17 block, fetus or placenta?
Which has 3B HSD block, fetus or placenta? Explain
CYP17 block- placenta
3B-HSD block- fetal zone
transitional zone expresses 3B HSD later in gestation and is site of cortisol syn.
Is the placenta a complete or incomplete endocrine organ?
placenta is incomplete endocrine organ bc it cannot make chol. and convert it all the way down through those pathways. cannot complete steroidogenesis- gets stuck at progesterone … but also “complete” in that can make SO many diff hormones.
What is Relaxin?
What produces it?
Describe its action.
Produced by both corpus luteum in response to HCG and by the placenta.
Inhibits myometrial contractions (ensure uterine quiescence in early pregnancy) relaxin really imp. at beginning stages for preventing myometrial contractions (that invasion of embryo in will stimulate myometrial contractions of endothelium and if those become too excessive, then miscarriage)
Relaxes pelvic bones and ligaments and softens cervix (may play a role in parturition)
May be involved in reversible hypertrophy of the heart (not proven)
Does prolactin come from the placenta or maternal pituitary or both?
What stimulates it?
PRL is not from the placenta but from maternal pituitary
Essential for mammotrophic effects of estrogen and progesterone
Stimulates lactogenic apparatus during gestation, but significant lactation is inhibited by high levels of progesterone and estrogen
Estrogen stimulates growth of the lactotrophs and increases PRL secretion
prolactin- imp. for maturation of maternal mammary glands in prep. for lactation.
How will high estrogen and progesterone affect lactation?
Prolactin stimulates lactogenic apparatus during gestation (and estrogen simulates PRL)
but significant lactation is inhibited by high levels of progesterone and estrogen
Describe the cardiovascular changes in pregnancy.
Cardiovascular
Increased cardiac output – increase in both heart rate and stroke volume
Catecholamines mediate chronotropic and inotropic increases
Some cardiomegaly (enlarged heart)
CV - one of largest ones.. need large amount of CO to perfuse placenta
alpha and beta ad. receptors up-regulated mediates contractility and timing.
heart will not get too big- bc mediated by action of relaxin.
In pregnancy, cardiac output increased but mean arterial pressure decreases. Explain how.
Mean Arterial Pressure decreases – TPR decreases more than CO increases.
compensatory - increase in volume, decrease in resistance.
veins become dilated and distended (partly bc expansion, skin stretching, have to maintain body temp, so vessels dilate to try to maintain)
spiral arteries have v low resistance now and v high capacity so they can perfuse placenta w high volumes
Venous pressure increases, 150% venous distension –
How do pulmonary pressures change in pregnancy?
Pulmonary pressures stays the same… off setting the increase in volume with a decrease in resistance
Describe changes in regional blood flow during pregnancy in uterus, skin and kidney and describe the effects of these changes.
Uterus – may receive 30% of cardiac output
Skin blood flow increases to maintain body temperature
Kidney blood flow increases and GFR increases.
Describe changes in blood volume during pregnancy. What hormone mediates this change?
How will hermatocrit (=total blood volume composed of RBC) change?
Increase in blood volume – 50% increase in 2nd trimester,
mediated by progesterone anticipates hemorrhage. Both plasma and RBC increase, with a net decrease in Hct
plasma increases but RBC also increase. RBC prod. stimulated by cortisol but bc placenta and total volume increase so much, actually get net decrease in hematocrit.
Describe the respiratory changes in pregnancy.
Changes in diaphragm.
Tidal volume?
Alveolar ventilation?
Will a pregnant woman have respiratory alkalosis?
Diaphragm is elevated by about 5 cm (40% reduction in expiratory reserve.
Increase in tidal volume with no change in respiratory frequency (deeper breaths)
Increased tidal volume results in increased alveolar ventilation
increase in tidal volume, no change in freq. so more alveolar ventilation
this is functional alkalosis (does not result in respiratory alkalosis bc there are compensatory changes in prod. of bicarb)
Describe gastrointestinal changes in pregnancy.
Protein requirements?
GI motility/transit time?
LES tone?
An additional 30g. of protein per day are required
Decreased GI motility, ( will affect smooth muscle cells of GI tract) providing a longer transit time and greater nutrition assimilation (constipation is a result).
Decreased LES (lower esophageal sphincter) tone, leading to greater reflux during pregnancy.
Describe endocrine changes during pregnancy. HPG axis?
How might anterior pituitary volume change?
HPG axis is suppressed by high concentrations of placental sex steroids.
There is a growth of pituitary lactotrophs and an increase in PRL secretion (GnRH suppression). Anterior pituitary volume increases by approx. 36%.
Describe the metabolic changes in pregnancy in the first half of pregnancy versus the second half.
First half of pregnancy - mother is in anabolic state
Normal or increased sensitivity to insulin
Increased fat deposition, glycogen stores
Promotes breast growth in mother and allows her to “stockpile”” nutrients to meet the demands of the enlarging fetus.
Second half of pregnancy – “accelerated starvation,” catabolic state characterized by insulin resistance.
Mediated by human chorionic somatomammotropin (a.k.a. hPL).
Increased plasma glucose and fatty acid levels.
mom stimulated to eat more bc counter-reg hormones increase from stressful state
Describe the 3 stages of labor.
Stage 1 – activation of the uterus
- Release from inhibitory actions of progesterone
- Uterine stretch from mature fetus stimulates oxytocin (Ferguson reflex)
- Fetal HPA axis is activated – CRH levels peak
fetal HPA axis activated. when CRH levels peak in placenta- this is thought to signal length of gestation.
clear connection between peak CRH levels and parturition.
Stage 2 – Positive feedback phase
-Widening (dilation) and thinning (effacement) of cervix
Stage 3 – Evacuation of uterus
-Expulsion of fetus from uterine compartment and release of placenta
What is Ferguson reflex? Does it stimulate parturition?
Uterine stretch from mature fetus stimulates oxytocin (Ferguson reflex)
does not stimulate parturition
Ferguson reflex- more stretch, oxytocin, smooth muscle contractions caused by oxytocin, more contractions cause more oxytocin and get positive feedback. happens but not thought to activate onset of labor
ferOT is released in bursts once labor begins, with increased frequency as labor continues.
The signal is the distention of cervix: the “Ferguson reflex.”
What is effacement?
Why/when does it occur?
Stage 2 parturition.
Stage 2 – Positive feedback phase
Widening (dilation) and thinning (effacement) of cervix
cervical muscles v thin (effacement) due to actions of pos. feedback from oxytocin. all stage 2 (usually fairly quickly in most women) activation can start early on and results in these “practice contractions” =Braxton hicks
What hormones are involves in the initiation and maintenance of labor and uterine evacuation?
Which are the most dominant in effect?
progesterone, E2, cortisol, relaxin, oxytocin, CRH, prostaglandins, catecholamines
The most dominant of these is the decrease in progesterone and increase in estrogen.
Describe the effects of estrogen in pregnancy related to OT.
Estrogen increases the number of OT receptors in myometrial tissues in pregnancy, increasing the potency of a given concentration of OT. (occurs throughout preg.)
Describe the changes in the uterus’ sensitivity to OT throughout pregnancy. When does it peak?
Uterus is insensitive to OT until 20 wks then sensitivity gradually increases to 80 fold at 36 weeks, plateaus just before parturition, and then increases to 200 fold in early labor.
What is Pitocin?
“Pitocin” – synthetic oxytocin used to induce labor
How is OT involved in lactation?
Suckling of breast will stimulate PVN and SON in hypothalmus and OT release from posterior pituitary.
OT will then stimulate myoepithelial cell contraction and milk ejection.
also imp. for ejection of milk. not important for making milk but is imp. for contractile muscles around alveoli (smooth muscle cells) to contract and eject milk from breast
Does OT initiate labor? How do levels change prior to labor?
Maternal OT not considered to initiate labor – levels do not increase prior to labor…
How are contractions stimulated?
OT stimulates prostaglandin release, which also stimulates contractions.
What promotes hemostasis of expelled placenta vessels?
Promotes hemostasis of expelled placenta vessels.
Describe the changes that the change in progesterone/E2 ratio stimulates?
Decrease in the progesterone/E2 ratio leads to increased local prostaglandins leading to an increase in myometrial cell Ca++, yielding more forceful myometrial cell contractions.
higher E than P, myometrium activated, up regulate OT receptors (so they will be v sensitive to OT) stimulate prostaglandins and cervical ripening (gets soft and allows for Ferg. reflex to kick in)
What is the last fetal organ to mature? What is required?
last thing to mature are lungs. has to happen by fetal HPA axis to make cortisol. that happens at the end - increased lung maturation and causes increased gluconeogenesis by the liver - allows fetus to start operating outside of fetal compartment and indep. of placenta
Increased pulmonary surfactant (lecithin)
occur at end. all increased by actions of cortisol. (this is why give premature babies prednisone … to facilitate maturation of lungs and increase prod. of surfactant)
have CRH being made in placenta, when peaks that will cause activation of HPA axis
cortisol transferred to fetus, cause loop…to make more CRH (unlike what happens in normal adult HPA axis)
Describe lactation.
How do hormones work to initiate this?
Initiated after delivery by decreased progesterone and E2
Repeated transient hyperprolactinemia sustains milk secretion
Suckling stimulates prolactin release- every time baby feeds, causes prolactin levels to increase again. this will sustain milk prod.
Prolactin – suppresses reproductive function (inhibits GnRH)
Prolactin –stimulates maternal behavior during pregnancy and after parturition .
Describe mammary gland remodeling.
at puberty some remodeling of breast due to E stimulated during pubertal development. branching and buds that proliferate highly during pregnancy..due to factors - prolactin being a big one but also HPL from placenta contributes
causes growth and diff. of breast tissue
What is the fundamental secretory unit of the breast?
Fundamental secretory unit of the breast–alveolus
Contractile myoepithelial cells, adipose cells
alveoli…these cells along edges prod. milk they become large cuboidal cells.
What is colostrum?
Colostrum – the first milk produced, contains little fat
first milk prod is colostrum…little fat but lots of antibodies protective for infant. secreted for first day or two after parturition.
Describe the contents of breast milk.
1% protein [casein, lactalbumin, lactoglobulin], 7% lactose, 4.5% fat, 70kcal/100ml, large amount of hormones
Up to 2000 mL per day may be produced by some mothers.
Which hormones are essential for continued milk production?
prolactin, cortisol, insulin
What causes milk “letdown” for infant?
Increased contraction of myoepithelial cells, alveoli and smooth muscle of duct walls causes “milk letdown” for infant.
Which hormone has both mammogenic effects, galactogenic effects?
Prolactin as a lactogenic hormone:
mammogenic effects-Breast development
galactogenic effects- Milk production
What would a dose of progestational hormone do?
Estrogenic hormone?
What would side effects would a progesterone-only pill have?
Progestational hormone prevents LH secretion (including blocking LH surge)
Estrogenic hormone inhibits FSH release. Estrogen also stabilizes endometrium and potentiates progestin action.
progesterone only- cause weight gain bc E is anorexic - P will be antagonizing effect of E and get weight gain as side effect
