Mechanisms Controlling Corpus Luteum Reg

Mechanisms Controlling Corpus Luteum Regression : 

Mechanisms Controlling Corpus Luteum Regression Presented by: Dr. Dhiren B. Bhoi M.V.Sc. Veterinary Gynaecology and Obstetrics E. Mail:-drdhirenvet@gmail.com

The Cyclic Ovary : 

The Cyclic Ovary Corpus Luteum

Outline : 

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 : 

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 : 

LH surge Primates

Structural Changes During Luteinization : 

Structural Changes During Luteinization A GC TC LC BV O

Steroidogenesis Before LH Surge : 

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 17a-HSD P450scc 3b-HSD Arom LH FSH P450scc 3b-HSD

Luteal Steroidogenesis : 

Luteal Steroidogenesis 17a-HSD Ch P A2 E2 Arom 17a-HSD Ch P A2 E2 Arom Ch: Cholesterol; P: Progesterone; A2: Endrogen; E2: Estradiol (Some Species) Large Luteal Cells Small Luteal Cells P450scc 3b-HSD P450scc 3b-HSD

Regulation of Corpus Luteum Function : 

Regulation of Corpus Luteum Function

Endocrine Effects of Progesterone : 

Endocrine Effects of Progesterone Contraction and Secretion Differentiation and Secretion Inhibits LH and FSH Secretion Lobuloalveolar Development For how long the corpus luteum secrets progesterone?

Slide 11: 

Estrogen Progesterone The Corpus Luteum is a Ephemeral Gland

Duration of Luteal Function Across Species : 

Duration of Luteal Function Across Species Physiological Review 79:263 Weeks Days/Weeks Weeks Weeks Months

Luteolysis : 

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?

A New Beginning : 

A New Beginning 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. : 

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 Progesterone Progesterone

Slide 16: 

Effects of Hysterectomy on the Activity of the Corpus Luteum

Unilateral Effect of Hysterectomy : 

Unilateral Effect of Hysterectomy 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?

Effect of Prostaglandin F2a Infusion on the Concentration of Progesterone in Ovaries of Pseudopregnant Rats : 

Effect of Prostaglandin F2a Infusion on the Concentration of Progesterone in Ovaries of Pseudopregnant Rats Pharris and Wyngarden Proc. 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 F2a Administration on the Duration of the Luteal Phase : 

Effect of Prostaglandin F2a Administration on the Duration of the Luteal Phase Ewe PGF2a must be transferred from a uterine horn to its adjacent ovary. Luteal Phase Luteal Phase Progesterone Progesterone How PGF2a is locally transported ?

Uterus-Ovary Connection : 

Uterus-Ovary Connection Ewe Ovarian Artery

Countercurrent Transfer Mechanism : 

Countercurrent Transfer Mechanism Nature 1972

Does PGF2a Fulfill the Role of Uterine Luteolytic Factor? : 

Does PGF2a 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).

A Practical Application of the Luteolytic Effect of Prostaglandin F2a : 

Estrus Synchronization of Cows Aim: 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 F2a I’m not in the mood. Bulls, Bulls, Bulls !!!!!!! Why PGF2a can be used to Synchronize Estrus in Cows?

PGF2a and Estrus Synchronization of Cows : 

PGF2a and Estrus Synchronization of Cows

Mechanism of Luteolytic Action of PGF2a : 

Mechanism of Luteolytic Action of PGF2a Bovine Pate & Keyes 2001

The Pregnant Rat Corpus Luteum : 

The Pregnant Rat Corpus Luteum

Regulation of Rat Corpus Luteum during Pregnancy : 

1 6 12 21 Progesterone Day of Pregnancy PRL LH D-PRL PL A A E A E P Regulation of Rat Corpus Luteum during Pregnancy PGF2a

Failure of Parturition in Mice Lacking theProstaglandin F2a Receptor : 

Sugimoto et al. Science, 1997) Days of pregnancy Serum Progesterone (ng/ml) +/+ PGF2aR -/- PGF2aR Parturition Failure of Parturition in Mice Lacking theProstaglandin F2a Receptor Which mechanism uses PGF2a to decrease progesterone secretion in rat at the end of pregnancy?

Slide 29: 

Days of pregnancy Steroids Levels (ng/ml) Progesterone 20a-dihydro Progesterone 18 19 20 21 22 20a-HSD L19 mRNA levels Prostaglandin F2a increases 20aHSD expression

20a-Hydroxysteriod Dehydrogenase20a-HSD, A New Player : 

20a-Hydroxysteriod Dehydrogenase20a-HSD, A New Player Progesterone 20a-dihydroprogesterone NADPH NADP 20a-HSD

20a-Hydroxysteriod DehydrogenaseExpression is Repressed During Pregnancy : 

Western Blot 20a-Hydroxysteriod DehydrogenaseExpression is Repressed During Pregnancy Now, who is responsible for this repression in the expression of 20a-HSD during pregnancy? Wiest, et al and Gibori et al.

20a-Hydroxysteriod DehydrogenaseExpression is Inhibited by Prolactin : 

PRL 20a Protein mRNA HYPOX 20a-Hydroxysteriod DehydrogenaseExpression is Inhibited by Prolactin Albarracin and Gibori. Endocrinology 1991 129:1821.

Regulation of 20a-HSD Expression in Rat Corpus Luteum : 

20a-HSD mRNA Regulation of 20a-HSD Expression in Rat Corpus Luteum ? PRL

Recommended Reading : 

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