The Luteal Phase of the Estrous and Menstrual Cycle John Parrish
Jan 06, 2016
The Luteal Phase of the Estrous and Menstrual Cycle
The Luteal Phase of the Estrous and Menstrual Cycle
John ParrishJohn Parrish
• steroid synthesis– progesterone
• collagenase– theca interna
• present 1-3 days following ovulation
• blood vessels in follicle wall rupture
• walls collapse
• cells intermix
• old basement membrane becomes connective tissue of CL
• increases in size– papilla forms
• composed of cells from the granulosa and theca interna
• progesterone production increases
• a small cavity may be present where the folliclular antrum was present
Luteal TissueLuteal Tissue
• Large cells from granulosa
• Small cells from the theca interna
• Large cells from granulosa
• Small cells from the theca interna
Mitochondria
SecretoryGranules
- Oxytocin- Relaxin
Functional Capability of CLFunctional Capability of CL• the number of luteal cells
– large cells undergo hypertrophy (3 fold)– small cells undergo hyperplasia (5 fold)
• vascularization of CL– Initiated by angiogenic factors from
follicle– Vascularity effects CL steroid synthesis
and delivery of hormones
• Insufficient CL function– Failure to maintain pregnancy– Important in domestic animals
• the number of luteal cells– large cells undergo hypertrophy (3 fold)– small cells undergo hyperplasia (5 fold)
• vascularization of CL– Initiated by angiogenic factors from
follicle– Vascularity effects CL steroid synthesis
and delivery of hormones
• Insufficient CL function– Failure to maintain pregnancy– Important in domestic animals
Progesterone Targets
Aveolar Development
Blocks EstrusNegative Feedback
Molecular Mechanism of LH on Luteal Cell
Receptor
PKA
NucleusDNA
Histones
Protein Synthesis(Enzymes) mRNA
Plasma Membrane
(cAMP second messenger)(cAMP second messenger)
Cholesterol
GAdenylate Cyclase
C
RcAMP
LH
ATP cAMP
(+ PO4)
R-ERProtein Synthesis
MitochondriaCholesterolPregnenolone
S-ERSteroid Synthesis
Progesterone
Molecular Mechanism of LH on Luteal Cell
Receptor
PKA
Protein Synthesis(Enzymes)
Plasma Membrane
(cAMP second messenger)(cAMP second messenger)
Cholesterol
GAdenylate Cyclase
C
RcAMP
LH
ATP cAMP
(+ PO4)
R-ERProtein Synthesis
MitochondriaCholesterolPregnenolone
S-ERSteroid Synthesis
Progesterone
CholChol
LDLLDL
CholChol
LDLLDL
Chol-EsterChol-Ester
LDLLDL
Chol Esterase
LuteolysisLuteolysis
• Uterus
• PGF2
• Oxytocin
• Uterus
• PGF2
• Oxytocin
Luteolysis in Cows,
Ewes, Sows
TotalHysterectomy
IpsilateralHysterectomy
ContralateralHysterectomy
NormalUterus
CL
CL Normal LifespanCL Normal Lifespan
CL Normal LifespanCL Normal Lifespan CL LifespanLonger
CL LifespanLonger
CL LifespanLonger
CL LifespanLonger
Similar to Gestation Length
>35 days
LuteolysisLuteolysis
• Uterus
• PGF2
• Oxytocin
• Uterus
• PGF2
• Oxytocin
Prostaglandin F2Control of Luteolysis
Progesterone fromCL stimulatesproduction of uterine PGF2afterday 15 in cow
Uterine Horn
UterineVein
Prostaglandin synthesisby uterine endometriumis released into the uterine vein.
Oviduct
Ovary
CorpusLuteum
PGF2 is picked up by ovarian artery through counter current exchangeand delivered back to theovary where it causeslysis of the CL
Uterine ArteryUterine Artery
Ovarian Pedicle
PGF
PGF into Artery
Luteolysis Mare
TotalHysterectomy
IpsilateralHysterectomy
ContralateralHysterectomy
NormalUterusCL
CL NormalLifespan
CL NormalLifespan
50% of CL’s Maintained
50% of CL’s Maintained
CL MaintainedCL Maintained
50% of CL’s Maintained
50% of CL’s Maintained
Blood Supply to Uterus and Ovary in the Mare
PGF Not Effective (Cow, Ewe, Mare)PGF Not Effective (Cow, Ewe, Mare)
PGF Not Effective (Sow)PGF Not Effective (Sow)
LuteolysisLuteolysis
• Uterus
• PGF2
• Oxytocin
• Uterus
• PGF2
• Oxytocin
Relationship of Oxytocin and PGF2
Uterus
Ovary
CL
PGF2
Anterior Pituitary
Posterior Pituitary
Oxytocin
LuteolysisLuteolysis
• decreased blood flow
• cellular response– apoptosis– progesterone synthesis
• Immune response– Lymphocytes– Macrophages
• decreased blood flow
• cellular response– apoptosis– progesterone synthesis
• Immune response– Lymphocytes– Macrophages
Molecular Mechanism of PGF (Ca2+ Second Messenger)
Molecular Mechanism of PGF (Ca2+ Second Messenger)
PLC
PIP2
Endoplasmic Reticulum
Ca2+
Protein Kinase C
Plasma Membrane
PGF
Re
cep
tor
G-proteinG-proteinDAG
IP3
R Ca2+
PlasmaMembrane
Ca2+
R
PIP2
CholesterolCholesterol
ProgesteroneProgesterone
Apoptosis
LuteolysisLuteolysis
• decreased blood flow
• cellular response– apoptosis– progesterone synthesis
• Immune response– Lymphocytes– Macrophages
• decreased blood flow
• cellular response– apoptosis– progesterone synthesis
• Immune response– Lymphocytes– Macrophages
Menstrual CycleMenstrual Cycle
FSHLHLH
EstradiolEstradiol
ProgesteroneProgesterone
FollicleOvulation
Corpus LuteumCorpus
Albicans
2 4 6 8 10 14 16 18 20 22 24 26 28 212
Anterior Pituitary
Hormones
Ovarian Hormones
Ovary
UterineEndo-
metrium
RecruitmentSelectionDominance
Recruitment
Luteolysis in the Primate• Does not require the uterus• CL lifespan in the human is 12-14 days unless
pregnancy occurs– In the absence of pregnancy, CL self destructs
– Possible intra-ovarian oxytocin receptors and PGF2 production
• Menstruation– Drop in P4 and E2
– Endometrial PGF2, vasoconstriction, necrosis
– Endometrial inflammation and tissue degeneration