Post on 12-Nov-2014
description
Mechanisms Controlling Corpus Luteum Regression
Dr. DHIREN B. BHOI
M.V.Sc., (Gynaecology)
E. Mail:-drdhirenvet@gmail.com
The Cyclic Ovary
Corpus Luteum
Corpus Albican
Outline• Corpus luteum.
– Where it came from?– What it secretes?– Which is its function?– How it is regulated?
• Luteolysis– Why should the corpus luteum capitulate?– Who dare to kill it?– Mechanisms of murder.
• The rat corpus luteum of Pregnancy– Regulation.– Mechanisms of regression.
Corpus Luteum Formation: Luteinization
• Luteinization in the process that transforms the granulosa and theca cells into luteal cells.
• This process is triggered by the surge of LH at mid-cycle.
• The LH surge causes profound changes in the follicles that become corpora lutea.
LH surge
Primates
Structural Changes During Luteinization
A
GC
TC LC
BV
O
Steroidogenesis Before LH Surge
A
GL
BM
TI
TE
Ch P A2
Ch P A2 E2
E2
A: Antrum; GL: Granulosas; BM; Basement Memb TI: Theca Int. TE: T Ext.; C: Capillaries Ch: Cholesterol; P: Progesterone; A2: Endrogen; E2: Estradiol
17-HSD
P450scc3-HSD
Arom
LH
FSH
P450scc3-HSD
Luteal Steroidogenesis
17-HSDCh P A2 E2Arom
17-HSDCh P A2 E2Arom
Ch: Cholesterol; P: Progesterone; A2: Endrogen; E2: Estradiol
(Some Species)
Large Luteal Cells
Small Luteal Cells
P450scc3-HSD
P450scc3-HSD
Regulation of Corpus Luteum Function
Species Luteotrophic Complex
Human LH
Sheep LH & GH
Pig Estradiol
Pseudopreg. Rabbit
Estradiol, LH
Pseudopreg. Rat/Mouse
Estradiol, Prolactin & LH
Endocrine Effects of Progesterone
Contraction
and Secretion
Differentiation
and Secretion
Inhibits LH
and FSH Secretion
Lobuloalveolar
Development
For how long the corpus luteumsecrets progesterone?
For how long the corpus luteumsecrets progesterone?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 281 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
EstrogenEstrogen
ProgesteroneProgesterone
The Corpus Luteum is a Ephemeral Gland
Duration of Luteal Function Across Species
Physiological Review 79:263
Weeks
Days/Weeks
Weeks
Weeks
Months
Luteolysis
• Luteolysis is the process by which the corpus luteum loses its capacity to synthesize and secrete progesterone.
• A luteolytic agent is any factor that can reduce luteal progesterone synthesis or secretion and/or prevent the action of a luteotrophic hormone.
Why mammals have developed mechanisms to curtail luteal function?Why mammals have developed mechanisms to curtail luteal function?
A New Beginning
Who is responsible for this decrease in CL function?Who is responsible for this decrease in CL function?
Progesterone inhibits LH and FSH Secretion
The Uterus Regulates the Life Span of the Corpus Luteum.
Luteal Phase Luteal Phase
Hysterectomy
1 10 20 1 10 20
Intact Animal Hysterectomized Animal
Pro
gest
eron
e
Pro
gest
eron
e
Effects of Hysterectomy on the Activity of the Corpus Luteum
Unilateral Effect of Hysterectomy
How can you explain these results?How can you explain these results?
There is a local transfer of a luteolytic hormone from one uterine horn and its adjacent ovary
The hormone released from one uterine horn is prevented from reaching the ovary on the contralateral side
The question is the identity of this factor?The question is the identity of this factor?
10
0
15
5
Saline PGF2
Pro
gest
eron
e C
once
ntr
atio
nu
g./g
of
Tis
sue
Effect of Prostaglandin F2 Infusion on the Concentration of Progesterone in Ovaries of
Pseudopregnant Rats
Pharris and WyngardenProc. Soc. Exp. Biol Med 1969:130:92
•It is abundant in the uterus.
•It has a short half-life in
circulation.
•It decreases progesterone.
Effect of Prostaglandin F2Administration on the Duration of the Luteal Phase
Ewe
AdministeredIn the Ovarian Artery
AdministeredSystemically
PGF2must be transferred from a uterine horn to its adjacent ovary.PGF2must be transferred from a uterine horn to its adjacent ovary.
Luteal PhaseLuteal Phase
Pro
gest
eron
e
Pro
gest
eron
eHow PGF2 is locally transported ?How PGF2 is locally transported ?
Uterus-Ovary Connection
Ewe
Ovarian
Artery
Countercurrent Transfer Mechanism
Nature 1972
Does PGF2 Fulfill the Role of Uterine Luteolytic Factor?
• It is produced by the uterus at the moment of luteolysis.
• Its administration causes premature luteolysis.
• It is transported from the uterus to the ovary by a countercurrent mechanism (not in all species).
Estrus Synchronization of CowsAim: To breed a high percentage of females in a short period of time
using artificial or natural insemination.
A Practical Application of the Luteolytic Effect of Prostaglandin F2
I’m not in the mood.
Bulls, Bulls, Bulls !!!!!!!
Why PGF2 can be used to Synchronize Estrus in Cows?
Why PGF2 can be used to Synchronize Estrus in Cows?
PGF2 and Estrus Synchronization of Cows
PGF2
Mechanism of Luteolytic Action of PGF2
BovinePate & Keyes 2001
The Pregnant Rat Corpus Luteum
1 6 12 21
Progesterone
Day of Pregnancy
PRL LH
D-PRL PL A
AE
A
E
P
Regulation of Rat Corpus Luteum during Pregnancy
PGF2
Sugimoto et al. Science, 1997)
0
10
20
30
40
50
Days of pregnancy17 19 2117 19 21
Ser
um
Pro
gest
eron
e(n
g/m
l)
+/+ PGF2R -/- PGF2R
Par
turi
tion
Failure of Parturition in Mice Lacking theProstaglandin F2 Receptor
Which mechanism uses PGF2 to decrease progesterone secretion in rat at the end of pregnancy?
Which mechanism uses PGF2 to decrease progesterone secretion in rat at the end of pregnancy?
0
50
100
150
200
250
Days of pregnancy
Steroids Levels(ng/ml)
Progesterone
20dihydroProgesterone
18 19 20 21 22
20-HSD
L19mRNA levels
PGF2
Prostaglandin F2 increases 20HSD expression
20-HSD
20-Hydroxysteriod Dehydrogenase20-HSD, A New Player
Progesterone 20-dihydroprogesterone
NADPH NADP
H3C
O
O
H3C
OH
20-HSD
Western Blot
20-Hydroxysteriod DehydrogenaseExpression is Repressed During Pregnancy
Now, who is responsible for this repression in the expression of 20-HSD during pregnancy?
Now, who is responsible for this repression in the expression of 20-HSD during pregnancy?
Wiest, et al and Gibori et al.
PRL
20
Protein mRNA
HYPOX
20-Hydroxysteriod DehydrogenaseExpression is Inhibited by Prolactin
Albarracin and Gibori. Endocrinology 1991 129:1821.
PGF2
20-HSD mRNA
Regulation of 20-HSD Expression in Rat Corpus Luteum
?
PRL
Recommended Reading
• Mechanisms Controlling the Function and Life Span of the Corpus Luteum. Physiological Reviews. 2000 80:1.
• Luteolysis: A Neuroendocrine-Mediate Event. Physiological Reviews. 1999 79:263.
• The Corpus Luteum of Pregnancy,G Gibori. In The Ovary. Ed. EY Adashi and PCK Leung. 1994 P. 261.
• The Corpus Luteum and Its Control in Infraprimate Species. In The Physiology of Reproduction. Ed. E Knobil and JD Neill. 1993. P. 781